Steroid 6.7.beta-epoxides as chemical intermediates

Abstract

The invention relates to a process for preparing a compound of general formula (Ia): wherein R<com:Sup>2< / com:Sup>, Y, R<com:Sup>4< / com:Sup> and R<com:Sup>5< / com:Sup> are as defined herein. The invention also relates to certain compounds perse. The compounds are intermediates in the synthesis of synthetic bile acids.

Description

STEROID 6.7.BETA-EPOXIDES AS CHEMICAL INTERMEDIATES Field of the invention The present invention relates to methods of preparing compounds which are intermediates in the synthesis of bile acid derivatives with pharmacological activity. In particular, the invention relates to methods of preparing intermediates in the synthesis of obeticholic acid and its analogues. The invention further relates to novel intermediates per se. Background of the invention Bile acids are steroid acids which are found in the bile of mammals and include compounds such as cholic acid, chenodeoxycholic acid, lithocholic acid and deoxycholic acid, all of which are found in humans. Many bile acids are natural ligands of the farnesoid X receptor (FXR) which is expressed in the liver and intestine of mammals, including humans. Bile acids are derivatives of steroids and are numbered in the same way. The following shows the general numbering system for steroids and the numbering of the carbon atoms in chenodeoxycholic acid. [Image disponible dans le document PDF, Image available in the PDF document] Agonists of FXR have been found to be of use in the treatment of cholestatic liver disorders including primary biliary cholangitis and non-alcoholic steatohepatitis (see review by Jonker et al., in Journal of Steroid Biochemistry & Molecular Biology, 2012, 130, 147-158). Ursodeoxycholic acid (UDCA), a bile acid originally isolated from the gall bladder of bears, is currently used in the treatment of cholestatic liver disorders, although it appears to be inactive at the FXR. As well as their action at the FXR, bile acids and their derivatives are also modulators of the G protein-coupled receptor TGR5. This is a member of the rhodopsin-like superfamily of G-protein coupled receptors and has an important role in the bile acid signalling network, which complements the role of the FXR. Because of the importance of FXR and TGR5 agonists in the treatment of cholestatic liver disorders, efforts have been made to develop new compounds which have agonist activity at these receptors. One particularly active compound is obeticholic acid, which is a potent agonist of both FXR and TGR5. Obeticholic acid is described in WO02 / 072598 and EP1568706, both of which describe a process for the preparation of obeticholic acid from 7-keto lithocholic acid, which is derived from cholic acid. Further processes for the production of obeticholic acid and its derivatives are described in WO2006 / 122977, US2009 / 0062256 and WO2013 / 192097 and all of these processes also start from 7-keto lithocholic acid. It is clear from the number of patent publications directed to processes for the production of obeticholic acid that it is by no means simple to synthesise this compound and indeed the process which is currently used starts from cholic acid, has 12 steps and a low overall yield. In addition to the inefficiency and high cost of this process, there are also problems with the cost and availability of the starting materials. Cholic acid, the current starting material for the production of obeticholic acid, is a natural bile acid which is usually obtained from the slaughter of cows and other animals. This means that the availability of cholic acid and other bile acids is limited by the number of cattle available for slaughter. Since the incidence of cholestatic liver disease is increasing worldwide, the demand for synthetic bile acids such as obeticholic acid is also likely to increase and it is doubtful whether the supply of naturally derived bile acids will continue to be sufficient to meet demand. Furthermore, the use of a starting material derived from animals means that there is the possibility of the contamination of the material with infectious agents such as viruses or prions, which can not only be hazardous to workers but could potentially contaminate the end products if steps are not taken to prevent this. Although some patients with cholestatic liver disease can be treated with ursodeoxycholic acid, this is also a natural bile acid and faces the same problems of limited availability and high cost. In an attempt to solve the problems associated with the use of bile acids as starting materials, the present inventors have devised a process for the synthesis of synthetic bile acid derivatives, such as obeticholic acid (OCA, referred to herein as compound (XA)), which uses plant sterols as starting materials. [Image disponible dans le document PDF, Image available in the PDF document] obeticholic acid (XA) The inventors have developed a process for the production of synthetic bile acids which proceeds via novel intermediates and which provides the final product in significantly higher yield than current processes. The process is flexible and can use a variety of different starting materials including animal, fungal and plant sterols. Suitable animal sterols which can be used as starting materials include deoxycholic acid, cholic acid, while fungal sterols include ergosterol. Plant sterols are widely available at significantly lower cost than bile acids and, indeed, are often waste products of other processes. Suitable plant sterol and plant sterol derivatives which can be used as starting materials include bis-norcholenol (also known as 20-hydroxymethylpregn-4-en-3-one), androstenedione, androstadienedione, dehydroepiandrosterone, stigmasterol, brassicasterol, campesterol and β-sitosterol. Our patent applications Nos. PCT / GB2015 / 053516 (WO2016 / 079517), PCT / GB2015 / 053517 (WO2016 / 079518), PCT / GB2015 / 053518 (WO2016 / 079519) and PCT / GB2015 / 053519 (WO2016 / 079520) relate to intermediates in the process of synthesizing obeticholic acid (and analogues) as well as to processes for preparing the intermediates and processes for converting them to the desired products. The present application relates to further compounds which are intermediates in the synthesis of obeticholic acid and analogues thereof. Summary of the invention In one aspect of the invention is provided a compound of general formula (la): [Image disponible dans le document PDF, Image available in the PDF document] (la) wherein: R<com:Sup>2< / com:Sup> is H, halo, OH or a protected OH group; Y is a bond, or a <com:Math><semantics>C1−20<annotation encoding="application / x-tex">C_{1-20}< / annotation>< / semantics>< / com:Math> alkylene, <com:Math><semantics>C2−20<annotation encoding="application / x-tex">C_{2-20}< / annotation>< / semantics>< / com:Math> alkenylene or <com:Math><semantics>C2−20<annotation encoding="application / x-tex">C_{2-20}< / annotation>< / semantics>< / com:Math> alkynylene linker group any of which is optionally substituted with one or more R<com:Sup>3< / com:Sup>; wherein each R<com:Sup>3< / com:Sup> is independently H, halo, OH, a protected OH group or NR<com:Sup>8< / com:Sup>R<com:Sup>9< / com:Sup>; wherein each of R<com:Sup>8< / com:Sup> and R<com:Sup>9< / com:Sup> is independently H, C<com:Sub>1-6< / com:Sub> alkyl, C(O)Ph, benzyl, phthalimide, tert-butyloxycarbonyl or carboxybenzyl; <com:Math><semantics>R4<annotation encoding="application / x-tex">R^4< / annotation>< / semantics>< / com:Math> is <com:Math><semantics>C(O)OR10<annotation encoding="application / x-tex">C(O)OR^{10}< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>OC(O)R10<annotation encoding="application / x-tex">OC(O)R^{10}< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>C(O)NR10R11<annotation encoding="application / x-tex">C(O)NR^{10}R^{11}< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>OR10<annotation encoding="application / x-tex">OR^{10}< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>OSi(R13)3<annotation encoding="application / x-tex">OSi(R^{13})_3< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>S(O)R10<annotation encoding="application / x-tex">S(O)R^{10}< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>SO2R10<annotation encoding="application / x-tex">SO_2R^{10}< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>OSO2R10<annotation encoding="application / x-tex">OSO_2R^{10}< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>SO3R10<annotation encoding="application / x-tex">SO_3R^{10}< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>OSO3R10<annotation encoding="application / x-tex">OSO_3R^{10}< / annotation>< / semantics>< / com:Math>, halo, <com:Math><semantics>CN<annotation encoding="application / x-tex">CN< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>C(O)R10<annotation encoding="application / x-tex">C(O)R^{10}< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>NR10R11<annotation encoding="application / x-tex">NR^{10}R^{11}< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>BR10R11<annotation encoding="application / x-tex">BR^{10}R^{11}< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>C(O)CH2N2<annotation encoding="application / x-tex">C(O)CH_2N_2< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−CH=CH2<annotation encoding="application / x-tex">-CH=CH_2< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−C≡CH<annotation encoding="application / x-tex">-C\equiv CH< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>CH[C(O)OR10]2<annotation encoding="application / x-tex">CH[C(O)OR^{10}]_2< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>CH(BR10R11)2<annotation encoding="application / x-tex">CH(BR^{10}R^{11})_2< / annotation>< / semantics>< / com:Math>, azide, <com:Math><semantics>NO2<annotation encoding="application / x-tex">NO_2< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>NR10C(O)NR10SO2R11<annotation encoding="application / x-tex">NR^{10}C(O)NR^{10}SO_2R^{11}< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>NR10C(O)NR10SO2N<annotation encoding="application / x-tex">NR^{10}C(O)NR^{10}SO_2N< / annotation>< / semantics>< / com:Math> R<com:Sup>10< / com:Sup>R<com:Sup>11< / com:Sup>, NR<com:Sup>10< / com:Sup>SO<com:Sub>2< / com:Sub>R<com:Sup>11< / com:Sup>, C(O)NR<com:Sup>10< / com:Sup>SO<com:Sub>2< / com:Sub>R<com:Sup>11< / com:Sup>, CH(XR<com:Sup>10< / com:Sup>)(XR<com:Sup>11< / com:Sup>), CH(R<com:Sup>10< / com:Sup>)(XR<com:Sup>11< / com:Sup>), phthalimide or a carboxylic acid mimetic group such as tetrazole; wherein each X is independently O, S or NR<com:Sup>8< / com:Sup>; wherein each R<com:Sup>10< / com:Sup> and R<com:Sup>11< / com:Sup> is independently: a. hydrogen; or b. C<com:Sub>1-20< / com:Sub> alkyl, C<com:Sub>3-7< / com:Sub> cycloalkyl, C<com:Sub>2-20< / com:Sub> alkenyl or C<com:Sub>2-20< / com:Sub> alkynyl, any of which is optionally substituted with one or more substituents selected from: <com:Math><semantics>C1−4<annotation encoding="application / x-tex">C_{1-4}< / annotation>< / semantics>< / com:Math> alkyl, <com:Math><semantics>C1−4<annotation encoding="application / x-tex">C_{1-4}< / annotation>< / semantics>< / com:Math> haloalkyl, halo, <com:Math><semantics>NO2<annotation encoding="application / x-tex">NO_2< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>CN<annotation encoding="application / x-tex">CN< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>OR19<annotation encoding="application / x-tex">OR^{19}< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>SR19<annotation encoding="application / x-tex">SR^{19}< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>C(O)OR19<annotation encoding="application / x-tex">C(O)OR^{19}< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>C(O)N(R19)2<annotation encoding="application / x-tex">C(O)N(R^{19})_2< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>SO2R19<annotation encoding="application / x-tex">SO_2R^{19}< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>OSO2R19<annotation encoding="application / x-tex">OSO_2R^{19}< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>SO3R19<annotation encoding="application / x-tex">SO_3R^{19}< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>OSO3R19<annotation encoding="application / x-tex">OSO_3R^{19}< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>N(R19)2<annotation encoding="application / x-tex">N(R^{19})_2< / annotation>< / semantics>< / com:Math> and a 6- to 14- membered aryl or 5- to 14-membered heteroaryl group, either of which is optionally substituted with one or more substituents selected from C<com:Sub>1-6< / com:Sub> alkyl, C<com:Sub>1-6< / com:Sub> haloalkyl, halo, NO<com:Sub>2< / com:Sub>, CN, OR<com:Sup>19< / com:Sup>, SR<com:Sup>19< / com:Sup>, <com:Math><semantics>C(O)OR19<annotation encoding="application / x-tex">C(O)OR^{19}< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>C(O)N(R19)2<annotation encoding="application / x-tex">C(O)N(R^{19})_2< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>SO2R19<annotation encoding="application / x-tex">SO_2R^{19}< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>SO3R19<annotation encoding="application / x-tex">SO_3R^{19}< / annotation>< / semantics>< / com:Math> and <com:Math><semantics>N(R19)2<annotation encoding="application / x-tex">N(R^{19})_2< / annotation>< / semantics>< / com:Math>; or C. a 6- to 14- membered aryl, 5- to 14-membered heteroaryl group or 3- to 10- membered heterocyclic ring, any of which is optionally substituted with one or more substituents selected from: C<com:Sub>1-6< / com:Sub> alkyl, C<com:Sub>3-7< / com:Sub> cycloalkyl, C<com:Sub>1-6< / com:Sub> haloalkyl, halo, NO<com:Sub>2< / com:Sub>, CN, OR<com:Sup>19< / com:Sup>, C=O, <com:Math><semantics>C(O)C1−4<annotation encoding="application / x-tex">C(O)C_{1-4}< / annotation>< / semantics>< / com:Math> alkyl, <com:Math><semantics>SR19<annotation encoding="application / x-tex">SR^{19}< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>C(O)OR19<annotation encoding="application / x-tex">C(O)OR^{19}< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>C(O)N(R19)2<annotation encoding="application / x-tex">C(O)N(R^{19})_2< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>SO2R19<annotation encoding="application / x-tex">SO_2R^{19}< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>SO3R19<annotation encoding="application / x-tex">SO_3R^{19}< / annotation>< / semantics>< / com:Math>, N(R<com:Sup>19< / com:Sup>)<com:Sub>2< / com:Sub>, phenyl, 5- to 14-membered heteroaryl, 3- to 10-membered heterocyclic ring, methylenedioxy and ethylenedioxy; or d. a polyethylene glycol residue; or e. when <com:Math><semantics>R4<annotation encoding="application / x-tex">R^4< / annotation>< / semantics>< / com:Math> is <com:Math><semantics>C(O)NR10R11<annotation encoding="application / x-tex">C(O)NR^{10}R^{11}< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>CH(XR10)(XR11)<annotation encoding="application / x-tex">CH(XR^{10})(XR^{11})< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>CH(R10)(XR11)<annotation encoding="application / x-tex">CH(R^{10})(XR^{11})< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>NR10R11<annotation encoding="application / x-tex">NR^{10}R^{11}< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>BR10R11<annotation encoding="application / x-tex">BR^{10}R^{11}< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>CH[C(O)OR10]2<annotation encoding="application / x-tex">CH[C(O)OR^{10}]_2< / annotation>< / semantics>< / com:Math> or <com:Math><semantics>CH(BR10R11)2<annotation encoding="application / x-tex">CH(BR^{10}R^{11})_2< / annotation>< / semantics>< / com:Math> an <com:Math><semantics>R10<annotation encoding="application / x-tex">R^{10}< / annotation>< / semantics>< / com:Math> and an <com:Math><semantics>R11<annotation encoding="application / x-tex">R^{11}< / annotation>< / semantics>< / com:Math> group, together with the atom or atoms to which they are attached, may combine to form a 3- to 10-membered heterocyclic ring; wherein each R<com:Sup>19< / com:Sup> is independently: H, C<com:Sub>1-6< / com:Sub> alkyl, C<com:Sub>1-6< / com:Sub> haloalkyl, or a 6- to 14- membered aryl or 5- to 14- membered heteroaryl group either of which is optionally substituted with one or more substituents selected from halo, C<com:Sub>1-6< / com:Sub> alkyl and C<com:Sub>1-6< / com:Sub> haloalkyl; and wherein each R<com:Sup>13< / com:Sup> is independently: a. <com:Math><semantics>C1−20<annotation encoding="application / x-tex">C_{1-20}< / annotation>< / semantics>< / com:Math> alkyl, <com:Math><semantics>C2−20<annotation encoding="application / x-tex">C_{2-20}< / annotation>< / semantics>< / com:Math> alkenyl or <com:Math><semantics>C2−20<annotation encoding="application / x-tex">C_{2-20}< / annotation>< / semantics>< / com:Math> alkynyl, any of which is optionally substituted with one or more substituents selected from: halo, <com:Math><semantics>NO2<annotation encoding="application / x-tex">NO_2< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>CN<annotation encoding="application / x-tex">CN< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>OR19<annotation encoding="application / x-tex">OR^{19}< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>SR19<annotation encoding="application / x-tex">SR^{19}< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>C(O)OR19<annotation encoding="application / x-tex">C(O)OR^{19}< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>C(O)N(R19)2<annotation encoding="application / x-tex">C(O)N(R^{19})_2< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>SO2R19<annotation encoding="application / x-tex">SO_2R^{19}< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>SO3R19<annotation encoding="application / x-tex">SO_3R^{19}< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>OSO3R19<annotation encoding="application / x-tex">OSO_3R^{19}< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>N(R19)2<annotation encoding="application / x-tex">N(R^{19})_2< / annotation>< / semantics>< / com:Math> and a 6- to 14- membered aryl or 5- to 14-membered heteroaryl group, either of which is optionally substituted with one or more substituents selected from C<com:Sub>1-6< / com:Sub> alkyl, <com:Math><semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics>< / com:Math> haloalkyl, halo, NO<com:Sub>2< / com:Sub>, CN, OR<com:Sup>19< / com:Sup>, SO<com:Sub>2< / com:Sub>R<com:Sup>19< / com:Sup>, SO<com:Sub>3< / com:Sub>R<com:Sup>19< / com:Sup> and N(R<com:Sup>19< / com:Sup>)<com:Sub>2< / com:Sub>; or b. a 6- to 14- membered aryl or 5- to 14-membered heteroaryl group either of which is optionally substituted with one or more substituents selected from: <com:Math><semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics>< / com:Math> alkyl, <com:Math><semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics>< / com:Math> haloalkyl, halo, <com:Math><semantics>NO2<annotation encoding="application / x-tex">NO_2< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>CN<annotation encoding="application / x-tex">CN< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>OR19<annotation encoding="application / x-tex">OR^{19}< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>SR19<annotation encoding="application / x-tex">SR^{19}< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>C(O)OR19<annotation encoding="application / x-tex">C(O)OR^{19}< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>C(O)N(R19)2<annotation encoding="application / x-tex">C(O)N(R^{19})_2< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>SO2R19<annotation encoding="application / x-tex">SO_2R^{19}< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>SO3R19<annotation encoding="application / x-tex">SO_3R^{19}< / annotation>< / semantics>< / com:Math> and <com:Math><semantics>N(R19)2<annotation encoding="application / x-tex">N(R^{19})_2< / annotation>< / semantics>< / com:Math>; wherein each R<com:Sup>19< / com:Sup> is independently: H, C<com:Sub>1-6< / com:Sub> alkyl or C<com:Sub>1-6< / com:Sub> haloalkyl; or Y and R<com:Sup>4< / com:Sup> together form a =CH<com:Sub>2< / com:Sub> group; and R<com:Sup>5< / com:Sup> is H, OH or a protected OH group; or a salt or isotopic variant thereof. In another aspect of the invention is provided a compound of general formula (I): 6 [Image disponible dans le document PDF, Image available in the PDF document] (l) wherein: R<com:Sup>2< / com:Sup> is H, halo, OH or a protected OH group; Y is a bond, or a <com:Math><semantics>C1−20<annotation encoding="application / x-tex">C_{1-20}< / annotation>< / semantics>< / com:Math> alkylene, <com:Math><semantics>C2−20<annotation encoding="application / x-tex">C_{2-20}< / annotation>< / semantics>< / com:Math> alkenylene or <com:Math><semantics>C2−20<annotation encoding="application / x-tex">C_{2-20}< / annotation>< / semantics>< / com:Math> alkynylene linker group any of which is optionally substituted with one or more R<com:Sup>3< / com:Sup>; wherein each R<com:Sup>3< / com:Sup> is independently halo, OR<com:Sup>8< / com:Sup> or NR<com:Sup>8< / com:Sup>R<com:Sup>9< / com:Sup>; wherein each of R<com:Sup>8< / com:Sup> and R<com:Sup>9< / com:Sup> is independently H or C<com:Sub>1-4< / com:Sub> alkyl; <com:Math><semantics>R4<annotation encoding="application / x-tex">R^4< / annotation>< / semantics>< / com:Math> is <com:Math><semantics>C(O)OR10<annotation encoding="application / x-tex">C(O)OR^{10}< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>OC(O)R10<annotation encoding="application / x-tex">OC(O)R^{10}< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>C(O)NR10R11<annotation encoding="application / x-tex">C(O)NR^{10}R^{11}< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>OR10<annotation encoding="application / x-tex">OR^{10}< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>OSi(R13)3<annotation encoding="application / x-tex">OSi(R^{13})_3< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>S(O)R10<annotation encoding="application / x-tex">S(O)R^{10}< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>SO2R10<annotation encoding="application / x-tex">SO_2R^{10}< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>OSO2R10<annotation encoding="application / x-tex">OSO_2R^{10}< / annotation>< / semantics>< / com:Math>, SO<com:Sub>3< / com:Sub>R<com:Sup>10< / com:Sup>, OSO<com:Sub>3< / com:Sub>R<com:Sup>10< / com:Sup>, halo, CN, C(O)R<com:Sup>10< / com:Sup>, CH(OR<com:Sup>10< / com:Sup>)(OR<com:Sup>11< / com:Sup>), CH(R<com:Sup>10< / com:Sup>)(OR<com:Sup>11< / com:Sup>), CH(SR<com:Sup>10< / com:Sup>)(SR<com:Sup>11< / com:Sup>), <com:Math><semantics>NR10R11<annotation encoding="application / x-tex">NR^{10}R^{11}< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>BR10R11<annotation encoding="application / x-tex">BR^{10}R^{11}< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>C(O)CH2N2<annotation encoding="application / x-tex">C(O)CH_2N_2< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−CH=CH2<annotation encoding="application / x-tex">-CH=CH_2< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−C≡CH<annotation encoding="application / x-tex">-C\equiv CH< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>CH[C(O)OR10]2<annotation encoding="application / x-tex">CH[C(O)OR^{10}]_2< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>CH(BR10R11)2<annotation encoding="application / x-tex">CH(BR^{10}R^{11})_2< / annotation>< / semantics>< / com:Math>, azide or a carboxylic acid mimetic group such as tetrazole; wherein each R<com:Sup>10< / com:Sup> and R<com:Sup>11< / com:Sup> is independently: a. hydrogen; or b. <com:Math><semantics>C1−20<annotation encoding="application / x-tex">C_{1-20}< / annotation>< / semantics>< / com:Math> alkyl, <com:Math><semantics>C2−20<annotation encoding="application / x-tex">C_{2-20}< / annotation>< / semantics>< / com:Math> alkenyl or <com:Math><semantics>C2−20<annotation encoding="application / x-tex">C_{2-20}< / annotation>< / semantics>< / com:Math> alkynyl, any of which is optionally substituted with one or more substituents selected from: halo, <com:Math><semantics>NO2<annotation encoding="application / x-tex">NO_2< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>CN<annotation encoding="application / x-tex">CN< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>OR19<annotation encoding="application / x-tex">OR^{19}< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>SR19<annotation encoding="application / x-tex">SR^{19}< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>C(O)OR19<annotation encoding="application / x-tex">C(O)OR^{19}< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>C(O)N(R19)2<annotation encoding="application / x-tex">C(O)N(R^{19})_2< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>SO2R19<annotation encoding="application / x-tex">SO_2R^{19}< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>SO3R19<annotation encoding="application / x-tex">SO_3R^{19}< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>OSO3R19<annotation encoding="application / x-tex">OSO_3R^{19}< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>N(R19)2<annotation encoding="application / x-tex">N(R^{19})_2< / annotation>< / semantics>< / com:Math> and a 6- to 14- membered aryl or 5- to 14-membered heteroaryl group, either of which is optionally substituted with one or more substituents selected from C<com:Sub>1-6< / com:Sub> alkyl, <com:Math><semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics>< / com:Math> haloalkyl, halo, NO<com:Sub>2< / com:Sub>, CN, OR<com:Sup>19< / com:Sup>, SR<com:Sup>19< / com:Sup>, C(O)OR<com:Sup>19< / com:Sup>, C(O)N(R<com:Sup>19< / com:Sup>)<com:Sub>2< / com:Sub>, <com:Math><semantics>SO2R19<annotation encoding="application / x-tex">SO_2R^{19}< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>SO3R19<annotation encoding="application / x-tex">SO_3R^{19}< / annotation>< / semantics>< / com:Math> and <com:Math><semantics>N(R19)2<annotation encoding="application / x-tex">N(R^{19})_2< / annotation>< / semantics>< / com:Math>; or C. a 6- to 14- membered aryl or 5- to 14-membered heteroaryl group either of which is optionally substituted with one or more substituents selected from: C<com:Sub>1-6< / com:Sub> alkyl, C<com:Sub>1-6< / com:Sub> haloalkyl, halo, NO<com:Sub>2< / com:Sub>, CN, OR<com:Sup>19< / com:Sup>, SR<com:Sup>19< / com:Sup>, C(O)OR<com:Sup>19< / com:Sup>, <com:Math><semantics>C(O)N(R19)2<annotation encoding="application / x-tex">C(O)N(R^{19})_2< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>SO2R19<annotation encoding="application / x-tex">SO_2R^{19}< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>SO3R19<annotation encoding="application / x-tex">SO_3R^{19}< / annotation>< / semantics>< / com:Math> and <com:Math><semantics>N(R19)2<annotation encoding="application / x-tex">N(R^{19})_2< / annotation>< / semantics>< / com:Math>; or d. a polyethylene glycol residue; or e. when R⁴ is <com:Math><semantics>C(O)NR10R11<annotation encoding="application / x-tex">C(O)NR^{10}R^{11}< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>CH(OR10)(OR11)<annotation encoding="application / x-tex">CH(OR^{10})(OR^{11})< / annotation>< / semantics>< / com:Math>, CH(R<com:Sup>10< / com:Sup>)(OR<com:Sup>11< / com:Sup>), CH(SR<com:Sup>10< / com:Sup>)(SR<com:Sup>11< / com:Sup>), NR<com:Sup>10< / com:Sup>R<com:Sup>11< / com:Sup>, BR<com:Sup>10< / com:Sup>R<com:Sup>11< / com:Sup>, CH[C(O)OR<com:Sup>10< / com:Sup>]<com:Sub>2< / com:Sub> or CH(BR<com:Sup>10< / com:Sup>R<com:Sup>11< / com:Sup>)<com:Sub>2< / com:Sub> an R<com:Sup>10< / com:Sup> and an R<com:Sup>11< / com:Sup> group, together with the atom or atoms to which they are attached, may combine to form a 3- to 10-membered heterocyclic ring; wherein each R<com:Sup>19< / com:Sup> is independently: H, C<com:Sub>1-6< / com:Sub> alkyl, C<com:Sub>1-6< / com:Sub> haloalkyl, or a 6- to 14- membered aryl or 5- to 14- membered heteroaryl group either of which is optionally substituted with one or more substituents selected from halo, C<com:Sub>1-6< / com:Sub> alkyl and C<com:Sub>1-6< / com:Sub> haloalkyl; and wherein each R<com:Sup>13< / com:Sup> is independently: a. <com:Math><semantics>C1−20<annotation encoding="application / x-tex">C_{1-20}< / annotation>< / semantics>< / com:Math> alkyl, <com:Math><semantics>C2−20<annotation encoding="application / x-tex">C_{2-20}< / annotation>< / semantics>< / com:Math> alkenyl or <com:Math><semantics>C2−20<annotation encoding="application / x-tex">C_{2-20}< / annotation>< / semantics>< / com:Math> alkynyl, any of which is optionally substituted with one or more substituents selected from: halo, <com:Math><semantics>NO2<annotation encoding="application / x-tex">NO_2< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>CN<annotation encoding="application / x-tex">CN< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>OR19<annotation encoding="application / x-tex">OR^{19}< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>SR19<annotation encoding="application / x-tex">SR^{19}< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>C(O)OR19<annotation encoding="application / x-tex">C(O)OR^{19}< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>C(O)N(R19)2<annotation encoding="application / x-tex">C(O)N(R^{19})_2< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>SO2R19<annotation encoding="application / x-tex">SO_2R^{19}< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>SO3R19<annotation encoding="application / x-tex">SO_3R^{19}< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>OSO3R19<annotation encoding="application / x-tex">OSO_3R^{19}< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>N(R19)2<annotation encoding="application / x-tex">N(R^{19})_2< / annotation>< / semantics>< / com:Math> and a 6- to 14- membered aryl or 5- to 14-membered heteroaryl group, either of which is optionally substituted with one or more substituents selected from C<com:Sub>1-6< / com:Sub> alkyl, <com:Math><semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics>< / com:Math> haloalkyl, halo, NO<com:Sub>2< / com:Sub>, CN, OR<com:Sup>19< / com:Sup>, SO<com:Sub>2< / com:Sub>R<com:Sup>19< / com:Sup>, SO<com:Sub>3< / com:Sub>R<com:Sup>19< / com:Sup> and N(R<com:Sup>19< / com:Sup>)<com:Sub>2< / com:Sub>; or b. a 6- to 14- membered aryl or 5- to 14-membered heteroaryl group either of which is optionally substituted with one or more substituents selected from: <com:Math><semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics>< / com:Math> alkyl, <com:Math><semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics>< / com:Math> haloalkyl, halo, <com:Math><semantics>NO2<annotation encoding="application / x-tex">NO_2< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>CN<annotation encoding="application / x-tex">CN< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>OR19<annotation encoding="application / x-tex">OR^{19}< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>SR19<annotation encoding="application / x-tex">SR^{19}< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>C(O)OR19<annotation encoding="application / x-tex">C(O)OR^{19}< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>C(O)N(R19)2<annotation encoding="application / x-tex">C(O)N(R^{19})_2< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>SO2R19<annotation encoding="application / x-tex">SO_2R^{19}< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>SO3R19<annotation encoding="application / x-tex">SO_3R^{19}< / annotation>< / semantics>< / com:Math> and <com:Math><semantics>N(R19)2<annotation encoding="application / x-tex">N(R^{19})_2< / annotation>< / semantics>< / com:Math>; wherein each R<com:Sup>19< / com:Sup> is independently: H, <com:Math><semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics>< / com:Math> alkyl or <com:Math><semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics>< / com:Math> haloalkyl; or Y and R<com:Sup>4< / com:Sup> together form a =CH<com:Sub>2< / com:Sub> group; and R<com:Sup>5< / com:Sup> is H, OH or a protected OH group; or a salt or isotopic variant thereof. Compounds of general formula (Ia) and (I) are of use as intermediates in the synthesis of obeticholic acid and analogues thereof. In another aspect of the invention is provided a process for preparing a compound of general formula (la) comprising: reacting a compound of general formula (IIa) with a halogenating agent followed by reaction with base to give a compound of general formula (la): [Image disponible dans le document PDF, Image available in the PDF document] wherein Y, R<com:Sup>2< / com:Sup>, R<com:Sup>4< / com:Sup> and R<com:Sup>5< / com:Sup> are as above defined for a compound of general formula (Ia). In another aspect of the invention is provided a process for preparing a compound of general formula (I) comprising: reacting a compound of general formula (II) with trichloroisocyanuric acid (TCCA), tribromoisocyanuric acid (TBCA), triiodoisocyanuric acid (TICA), 1,3-dichloro-5,5- dimethylhydantoin (DCDMH), 1,3-dibromo-5,5-dimethylhydantoin (DBDMH), or 1,3- diiodo-5,5-dimethylhydantoin (DIDMH) followed by reaction with base to give a compound of general formula (I): [Image disponible dans le document PDF, Image available in the PDF document] wherein Y, R<com:Sup>2< / com:Sup>, R<com:Sup>4< / com:Sup> and R<com:Sup>5< / com:Sup> are as above defined for a compound of general formula (I). In another aspect of the invention is provided a process for preparing a compound of general formula (la) comprising the steps of: (A) reacting a compound of general formula (IIa) with a halogenating agent to give a compound of general formula (IIIxa) and / or a compound of general formula (IIIya) [Image disponible dans le document PDF, Image available in the PDF document] wherein X is Cl, Br or I; and wherein Y, R<com:Sup>2< / com:Sup>, R<com:Sup>4< / com:Sup> and R<com:Sup>5< / com:Sup> are as above defined for a compound of general formula (la) and (B) reacting a compound of general formula (Illxa) and / or a compound of general formula (IIIya) with a base to form a compound of general formula (la): [Image disponible dans le document PDF, Image available in the PDF document] wherein X is CI, Br or I; and wherein Y, R<com:Sup>2< / com:Sup>, R<com:Sup>4< / com:Sup> and R<com:Sup>5< / com:Sup> are as above defined for a compound of general formula (Ia). In another aspect of the invention is provided a process for preparing a compound of general formula (I) comprising the steps of: (A) reacting a compound of general formula (II) with trichloroisocyanuric acid (TCCA), tribromoisocyanuric acid (TBCA), triiodoisocyanuric acid (TICA), 1,3-dichloro-5,5- dimethylhydantoin (DCDMH), 1,3-dibromo-5,5-dimethylhydantoin (DBDMH), or 1,3- diiodo-5,5-dimethylhydantoin (DIDMH) to give a compound of general formula (IIIx) and / or a compound of general formula (IIIy) [Image disponible dans le document PDF, Image available in the PDF document] wherein X is Cl, Br or I; and wherein Y, R<com:Sup>2< / com:Sup>, R<com:Sup>4< / com:Sup> and R<com:Sup>5< / com:Sup> are as above defined for a compound of general formula (I) and (B) reacting a compound of general formula (IIIx) and / or a compound of general formula (IIIy) with a base to form a compound of general formula (I): [Image disponible dans le document PDF, Image available in the PDF document] wherein X is CI, Br or I; and wherein Y, R<com:Sup>2< / com:Sup>, R<com:Sup>4< / com:Sup> and R<com:Sup>5< / com:Sup> are as above defined for a compound of general formula (I). In a further aspect of the invention is provided compounds of general formula (IIIxa) and general formula (IIIya), and compounds of general formula (IIIx) and general formula (IIIy) per se, such compounds being useful as intermediates in the synthesis of a compound of general formula (la) or a compound of general formula (l), respectively. Thus, in one aspect of the invention is provided a compound of general formula (IIIxa): [Image disponible dans le document PDF, Image available in the PDF document] (IIIxa) or a salt an isotopic variant thereof, wherein X is CI, Br or I; and wherein Y, R<com:Sup>2< / com:Sup>, R<com:Sup>4< / com:Sup> and R<com:Sup>5< / com:Sup> are as above defined for a compound of general formula (Ia). In one aspect of the invention is provided a compound of general formula (IIIx): [Image disponible dans le document PDF, Image available in the PDF document] (IIIX) or a salt an isotopic variant thereof, wherein X is CI, Br or I; and wherein Y, R<com:Sup>2< / com:Sup>, R<com:Sup>4< / com:Sup> and R<com:Sup>5< / com:Sup> are as above defined for a compound of general formula (I). In another aspect of the invention is provided a compound of general formula (IIIya): [Image disponible dans le document PDF, Image available in the PDF document] (Illya) or a salt or an isotopic variant thereof, wherein X is CI, Br or I; and wherein Y, R<com:Sup>2< / com:Sup>, R<com:Sup>4< / com:Sup> and R<com:Sup>5< / com:Sup> are as above defined for a compound of general formula (Ia). In another aspect of the invention is provided a compound of general formula (IIIy): [Image disponible dans le document PDF, Image available in the PDF document] (IIIy) or a salt or an isotopic variant thereof, wherein X is Cl, Br or I; and wherein Y, R<com:Sup>2< / com:Sup>, R<com:Sup>4< / com:Sup> and R<com:Sup>5< / com:Sup> are as above defined for a compound of general formula (I). In one embodiment is provided a mixture of a compound of formula (Illxa) and a compound of general formula (IIIya). In one embodiment is provided a mixture of a compound of formula (IIIx) and a compound of general formula (IIIy). In one embodiment is provided a mixture comprising a compound of formula (Illxa) and a compound of general formula (IIIya). In one embodiment is provided a mixture comprising a compound of formula (IIIx) and a compound of general formula (IIIy). In another aspect of the invention is provided a process for preparing a compound of general formula (la) comprising the steps of: (A) reacting a compound of general formula (IIa) with a halogenating agent to give a compound of general formula (IIIxa) and / or a compound of general formula (IIIya) and / or a compound of general formula (IIIxz) and / or a compound of general formula (IIIyz): [Image disponible dans le document PDF, Image available in the PDF document] wherein X is CI, Br or I; R<com:Sup>40< / com:Sup> is C(O)H, C(O)C<com:Sub>1-4< / com:Sub> alkyl, C(O)phenyl, C(O)benzyl, phenyl, benzyl, C<com:Sub>2-4< / com:Sub> alkenyl or SO<com:Sub>2< / com:Sub>CF<com:Sub>3< / com:Sub>; wherein C(O)phenyl, C(O)benzyl, phenyl and benzyl are optionally substituted with one or more substituents selected from C<com:Sub>1-4< / com:Sub> alkyl, OC<com:Sub>1-4< / com:Sub> alkyl, halo, nitro, C<com:Sub>1-4< / com:Sub> haloalkyl and OC<com:Sub>1-4< / com:Sub> haloalkyl; and wherein Y, R<com:Sup>2< / com:Sup>, R<com:Sup>4< / com:Sup> and R<com:Sup>5< / com:Sup> are as above defined for a compound of general formula (Ia) and (B) reacting a compound of general formula (IIIxa) and / or a compound of general formula (IIIxa) and / or a compound of general formula (IIIxz) and / or a compound of general formula (IIIyz) with a base to form a compound of general formula (Ia): [Image disponible dans le document PDF, Image available in the PDF document] wherein X is CI, Br or I; R<com:Sup>40< / com:Sup> is C(O)H, C(O)C<com:Sub>1-4< / com:Sub> alkyl, C(O)phenyl, C(O)benzyl, phenyl, benzyl, C<com:Sub>2-4< / com:Sub> alkenyl or SO<com:Sub>2< / com:Sub>CF<com:Sub>3< / com:Sub>; wherein C(O)phenyl, C(O)benzyl, phenyl and benzyl are optionally substituted with one or more substituents selected from C<com:Sub>1-4< / com:Sub> alkyl, OC<com:Sub>1-4< / com:Sub> alkyl, halo, nitro, C<com:Sub>1-4< / com:Sub> haloalkyl and OC<com:Sub>1-4< / com:Sub> haloalkyl; and wherein Y, R<com:Sup>2< / com:Sup>, R<com:Sup>4< / com:Sup> and R<com:Sup>5< / com:Sup> are as above defined for a compound of general formula (Ia). In this embodiment, suitably step (A) is carried out in the presence of <com:Math><semantics>HOC(O)Rx<annotation encoding="application / x-tex">HOC(O)R^x< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>HORy<annotation encoding="application / x-tex">HOR^y< / annotation>< / semantics>< / com:Math>, or HSO<com:Sub>3< / com:Sub>R<com:Sup>z< / com:Sup>; wherein R<com:Sup>x< / com:Sup> is H, C<com:Sub>1-4< / com:Sub> alkyl (e.g. methyl or ethyl), phenyl or benzyl; R<com:Sup>y< / com:Sup> is phenyl, benzyl or C<com:Sub>2-4< / com:Sub> alkene (e.g. allyl); and R<com:Sup>z< / com:Sup> is CF<com:Sub>3< / com:Sub>, wherein phenyl and benzyl are optionally substituted with one or more substituents selected from C<com:Sub>1-4< / com:Sub> alkyl, OC<com:Sub>1-4< / com:Sub> alkyl, halo, nitro, C<com:Sub>1-4< / com:Sub> haloalkyl and OC<com:Sub>1-4< / com:Sub> haloalkyl. HOR<com:Sup>x< / com:Sup>, HOR<com:Sup>y< / com:Sup> or HSO<com:Sub>3< / com:Sub>R<com:Sup>z< / com:Sup> may be present as an additive in the reaction (suitably in the absence of water and in the presence of an aprotic solvent) or as the reaction solvent itself. In this aspect of the invention, mixtures of compounds of general formula (IIIxa) and / or, compounds of general formula (IIIya) and / or compounds of general formula (IIIxz) and / or compounds of general formula (IIIyz) are formed in step A and then reacted in step B. In one embodiment, the process further includes the step of removal of group R<com:Sup>40< / com:Sup> before treatment with base. In one embodiment, the process further includes the step of removal of group R<com:Sup>40< / com:Sup> before step (B) is carried out. In one aspect of the invention is provided a compound of general formula (IIIxz): [Image disponible dans le document PDF, Image available in the PDF document] (IIIxz) or a salt an isotopic variant thereof, wherein X is CI, Br or I; <com:Math><semantics>R40<annotation encoding="application / x-tex">R^{40}< / annotation>< / semantics>< / com:Math> is C(O)H, C(O)C<com:Sub>1-4< / com:Sub> alkyl, C(O)phenyl, C(O)benzyl, phenyl, benzyl, C<com:Sub>2-4< / com:Sub> alkenyl or SO<com:Sub>2< / com:Sub>CF<com:Sub>3< / com:Sub>; wherein C(O)phenyl, C(O)benzyl, phenyl and benzyl are optionally substituted with one or more substituents selected from C<com:Sub>1-4< / com:Sub> alkyl, OC<com:Sub>1-4< / com:Sub> alkyl, halo, nitro, C<com:Sub>1-4< / com:Sub> haloalkyl and OC<com:Sub>1-4< / com:Sub> haloalkyl; and wherein Y, R<com:Sup>2< / com:Sup>, R<com:Sup>4< / com:Sup> and R<com:Sup>5< / com:Sup> are as above defined for a compound of general formula (Ia). In another aspect of the invention is provided a compound of general formula (IIIyz): [Image disponible dans le document PDF, Image available in the PDF document] (Illyz) or a salt or an isotopic variant thereof, wherein X is CI, Br or I; R<com:Sup>40< / com:Sup> is C(O)H, C(O)C<com:Sub>1-4< / com:Sub> alkyl, C(O)phenyl, C(O)benzyl, phenyl, benzyl, C<com:Sub>2-4< / com:Sub> alkenyl, or SO<com:Sub>2< / com:Sub>CF<com:Sub>3< / com:Sub>; wherein C(O)phenyl, C(O)benzyl, phenyl and benzyl are optionally substituted with one or more substituents selected from C<com:Sub>1-4< / com:Sub> alkyl, OC<com:Sub>1-4< / com:Sub> alkyl, halo, nitro, C<com:Sub>1-4< / com:Sub> haloalkyl and OC<com:Sub>1-4< / com:Sub> haloalkyl; and wherein Y, R<com:Sup>2< / com:Sup>, R<com:Sup>4< / com:Sup> and R<com:Sup>5< / com:Sup> are as above defined for a compound of general formula (Ia). In one embodiment is provided a mixture comprising a compound of formula (Illxz) and a compound of general formula (IIIyz). Compounds of general formulae (Ia) and (I) are of use in the synthesis of obeticholic acid and analogues thereof. Compounds of general formula (Ia) are of use in the preparation of compounds of general formula (Xa): [Image disponible dans le document PDF, Image available in the PDF document] (Xa) or a salt or an isotopic variant thereof, wherein, <com:Math><semantics>R1<annotation encoding="application / x-tex">R^1< / annotation>< / semantics>< / com:Math> is <com:Math><semantics>C1−4<annotation encoding="application / x-tex">C_{1-4}< / annotation>< / semantics>< / com:Math> alkyl, <com:Math><semantics>C2−4<annotation encoding="application / x-tex">C_{2-4}< / annotation>< / semantics>< / com:Math> alkenyl or <com:Math><semantics>C2−4<annotation encoding="application / x-tex">C_{2-4}< / annotation>< / semantics>< / com:Math> alkynyl optionally substituted with one or more substituents selected from halo, OR<com:Sup>6< / com:Sup> and NR<com:Sup>6< / com:Sup>R<com:Sup>7< / com:Sup>; wherein each of <com:Math><semantics>R6<annotation encoding="application / x-tex">R^6< / annotation>< / semantics>< / com:Math> and <com:Math><semantics>R7<annotation encoding="application / x-tex">R^7< / annotation>< / semantics>< / com:Math> is independently H or <com:Math><semantics>C1−4<annotation encoding="application / x-tex">C_{1-4}< / annotation>< / semantics>< / com:Math> alkyl; R<com:Sup>2< / com:Sup> is H, halo or OH; and Y<com:Sup>1< / com:Sup> is a bond, or a C<com:Sub>1-20< / com:Sub> alkylene linker group which is optionally substituted with one or more R<com:Sup>3< / com:Sup>; or Y<com:Sup>1< / com:Sup> and R<com:Sup>4< / com:Sup> together form a =CH<com:Sub>2< / com:Sub> group; and R<com:Sup>5a< / com:Sup> is H or OH; wherein R<com:Sup>3< / com:Sup> and R<com:Sup>4< / com:Sup> are as described above for a compound of general formula (la). Compounds of general formula (I) are of use in the preparation of compounds of general formula (X): [Image disponible dans le document PDF, Image available in the PDF document] (X) or a salt or an isotopic variant thereof, wherein, R<com:Sup>1< / com:Sup> is C<com:Sub>1-4< / com:Sub> alkyl optionally substituted with one or more substituents selected from halo, OR<com:Sup>6< / com:Sup> and NR<com:Sup>6< / com:Sup>R<com:Sup>7< / com:Sup>; wherein each of R<com:Sup>6< / com:Sup> and R<com:Sup>7< / com:Sup> is independently H or C<com:Sub>1-4< / com:Sub> alkyl; R<com:Sup>2< / com:Sup> is H, halo or OH; and Y<com:Sup>1< / com:Sup> is a bond, or a C<com:Sub>1-20< / com:Sub> alkylene linker group which is optionally substituted with one or more R<com:Sup>3< / com:Sup>; or Y<com:Sup>1< / com:Sup> and R<com:Sup>4< / com:Sup> together form a =CH<com:Sub>2< / com:Sub> group; and R<com:Sup>5a< / com:Sup> is H or OH; wherein R<com:Sup>3< / com:Sup> and R<com:Sup>4< / com:Sup> are as described above for a compound of general formula (I). In one aspect of the invention is provided a process for preparing a compound of general formula (Xa) from a compound of formula (la): [Image disponible dans le document PDF, Image available in the PDF document] the process comprising the steps of: (a) selective alkylation of a compound of general formula (la) with an organometallic regent to give a compound of general formula (IVa): [Image disponible dans le document PDF, Image available in the PDF document] (IVa) wherein R<com:Sup>1< / com:Sup> is as defined for a compound of formula (Xa); and Y, R<com:Sup>2< / com:Sup>, R<com:Sup>4< / com:Sup> and R<com:Sup>5< / com:Sup> are as defined for a compound of general formula (Ia); (b) reducing the compound of general formula (IVa) using a suitable reducing agent to give a compound of general formula (Va): [Image disponible dans le document PDF, Image available in the PDF document] (Va) wherein R<com:Sup>1< / com:Sup> and Y<com:Sup>1< / com:Sup> are as defined for a compound of formula (Xa); and R<com:Sup>2< / com:Sup>, R<com:Sup>4< / com:Sup> and R<com:Sup>5< / com:Sup> are as defined for a compound of general formula (Ia); (c) oxidising the compound of general formula (Va) using a suitable oxidising agent to give a compound of general formula (VIa): [Image disponible dans le document PDF, Image available in the PDF document] (Vla) wherein R<com:Sup>1< / com:Sup> and Y<com:Sup>1< / com:Sup> are as defined for a compound of formula (Xa); and R<com:Sup>2< / com:Sup>, R<com:Sup>4< / com:Sup> and R<com:Sup>5< / com:Sup> are as defined for a compound of general formula (Ia); (d) reduction of the compound of general formula (VIa) using a suitable reducing agent and, where R<com:Sup>2< / com:Sup> and / or R<com:Sup>5< / com:Sup> is a protected OH, removal of the protecting group(s), to give a compound of general formula (Xa) as defined above, wherein removal of the protecting group can take place before or after the reduction; and wherein the process further includes one or more optional steps of converting compounds of general formulae (Ia), (IVa), (Va), (VIa), and (Xa) to other compounds of general formulae (Ia), (IVa), (Va), (VIa), and (Xa). The optional steps consist of reacting the side chains of the compounds of general formulae (Ia), (IVa), (Va), (VIa), and (Xa) as described below to arrive at compounds with alternative Y and / or R4 moieties. In one aspect of the invention is provided a process for preparing a compound of general formula (X) from a compound of formula (I): [Image disponible dans le document PDF, Image available in the PDF document] the process comprising the steps of: (a) selective alkylation of a compound of general formula (I) with an organometallic regent to give a compound of general formula (IV): [Image disponible dans le document PDF, Image available in the PDF document] (IV) wherein R<com:Sup>1< / com:Sup> is as defined for a compound of formula (X); and Y, R<com:Sup>2< / com:Sup>, R<com:Sup>4< / com:Sup> and R<com:Sup>5< / com:Sup> are as defined for a compound of general formula (I); (b) reducing the compound of general formula (IV) using a suitable reducing agent to give a compound of general formula (V): [Image disponible dans le document PDF, Image available in the PDF document] (V) wherein <com:Math><semantics>R1<annotation encoding="application / x-tex">R^1< / annotation>< / semantics>< / com:Math> and <com:Math><semantics>Y1<annotation encoding="application / x-tex">Y^1< / annotation>< / semantics>< / com:Math> are as defined for a compound of formula (X); and R<com:Sup>2< / com:Sup>, R<com:Sup>4< / com:Sup> and R<com:Sup>5< / com:Sup> are as defined for a compound of general formula (I); (c) oxidising the compound of general formula (V) using a suitable oxidising agent to give a compound of general formula (VI): [Image disponible dans le document PDF, Image available in the PDF document] (VI) wherein R<com:Sup>1< / com:Sup> and Y<com:Sup>1< / com:Sup> are as defined for a compound of formula (X); and R<com:Sup>2< / com:Sup>, R<com:Sup>4< / com:Sup> and R<com:Sup>5< / com:Sup> are as defined for a compound of general formula (I); (d) reduction of the compound of general formula (VI) using a suitable reducing agent and, where R<com:Sup>2< / com:Sup> and / or R<com:Sup>5< / com:Sup> is a protected OH, removal of the protecting group(s), to give a compound of general formula (X) as defined above, wherein removal of the protecting group can take place before or after the reduction; and wherein the process further includes one or more optional steps of converting compounds of general formulae (I), (IV), (V), (VI), and (X) to other compounds of general formulae (I), (IV), (V), (VI), and (X). The optional steps consist of reacting the side chains of the compounds of general formulae (I), (IV), (V), (VI), and (X) as described below to arrive at compounds with alternative Y and / or R<com:Sup>4< / com:Sup> moieties. In a further aspect of the invention is provided a compound of general formula (IVa) and a compound of general formula (Va) per se, and a compound of general formula (IV) and a compound of general formula (V) per se such compounds being useful as intermediates in the synthesis of a compound of general formula (Xa) and a compound of general formula (X), respectively. Thus, in one aspect of the invention is provided a compound of general formula (IVa): [Image disponible dans le document PDF, Image available in the PDF document] (IVa) or a salt an isotopic variant thereof, wherein R<com:Sup>1< / com:Sup> is as defined for a compound of general formula (Xa); and wherein Y, R<com:Sup>2< / com:Sup>, R<com:Sup>4< / com:Sup> and R<com:Sup>5< / com:Sup> are as defined for a compound of general formula (Ia). In one aspect of the invention is provided a compound of general formula (IV): [Image disponible dans le document PDF, Image available in the PDF document] (IV) or a salt an isotopic variant thereof, wherein R<com:Sup>1< / com:Sup> is as defined for a compound of general formula (X); and wherein Y, R<com:Sup>2< / com:Sup>, R<com:Sup>4< / com:Sup> and R<com:Sup>5< / com:Sup> are as defined for a compound of general formula (I). In another aspect of the invention is provided a compound of general formula (Va): [Image disponible dans le document PDF, Image available in the PDF document] (Va) or a salt an isotopic variant thereof, wherein R¹ and Y¹ are as defined for a compound of formula (Xa); and R<com:Sup>2< / com:Sup>, R<com:Sup>4< / com:Sup> and R<com:Sup>5< / com:Sup> are as defined for compounds of general formula (la). In another aspect of the invention is provided a compound of general formula (V): [Image disponible dans le document PDF, Image available in the PDF document] (V) or a salt an isotopic variant thereof, wherein R<com:Sup>1< / com:Sup> and Y<com:Sup>1< / com:Sup> are as defined for a compound of formula (X); and R<com:Sup>2< / com:Sup>, R<com:Sup>4< / com:Sup> and R<com:Sup>5< / com:Sup> are as defined for compounds of general formula (I). Figures Figure 1: shows respresentative conversions of a compound of general formula (IIa) or general formula (II) in which the side chain is -CH<com:Sub>2< / com:Sub>OH to other compounds of general formula (IIa) or general formula (II), respectively, with different side chains. Figure 2: shows the <com:Sup>1< / com:Sup>H NMR spectrum of (6β, 7α, 22E)-6-acetoxy-7-chloro-3-oxo-4,22- choladien-24-oic acid ethyl ester (see Example 2). Figure 3: shows the <com:Sup>13< / com:Sup>C NMR spectrum of (6β, 7α, 22E)-6-acetoxy-7-chloro-3-oxo-4,22- choladien-24-oic acid ethyl ester (see Example 2). Figure 4: shows the characteristic C4 protons in the <com:Sup>1< / com:Sup>H NMR of a 2:1 mixture of (6β,7β) and <com:Math><semantics>(6α,7α)<annotation encoding="application / x-tex">(6\alpha,7\alpha)< / annotation>< / semantics>< / com:Math> isomers of <com:Math><semantics>(22E)<annotation encoding="application / x-tex">(22E)< / annotation>< / semantics>< / com:Math>-6,7-epoxy-3-oxo-4,22-choladien-24-oic acid ethyl ester (See Example 4). Figure 5: shows an <com:Sup>1< / com:Sup>H NMR comparison of <com:Math><semantics>(5β,6α)<annotation encoding="application / x-tex">(5\beta, 6\alpha)< / annotation>< / semantics>< / com:Math>-3,7-dioxo-6-ethyl-cholan-24-oic acid prepared from <com:Math><semantics>(6α,7α,22E)<annotation encoding="application / x-tex">(6\alpha, 7\alpha, 22E)< / annotation>< / semantics>< / com:Math>-6,7-epoxy-3-oxo-4,22-choladien-24-oic acid ethyl ester (alpha) and (6β, 7β, 22E)-6,7-epoxy-3-oxo-4,22-choladien-24-oic acid ethyl ester (beta). Figure 6: shows a <com:Sup>13< / com:Sup>C NMR comparison of <com:Math><semantics>(5β,6α)<annotation encoding="application / x-tex">(5\beta, 6\alpha)< / annotation>< / semantics>< / com:Math>-3,7-dioxo-6-ethyl-cholan-24-oic acid prepared from <com:Math><semantics>(6α,7α,22E)<annotation encoding="application / x-tex">(6\alpha, 7\alpha, 22E)< / annotation>< / semantics>< / com:Math>-6,7-epoxy-3-oxo-4,22-choladien-24-oic acid ethyl ester (alpha) and (6β, 7β, 22E)-6,7-epoxy-3-oxo-4,22-choladien-24-oic acid ethyl ester (beta). Detailed description of the invention In the present specification, except where the context requires otherwise due to express language or necessary implication, the word "comprises", or variations such as "comprises" or "comprising" is used in an inclusive sense i.e. to specify the presence of the stated features but not to preclude the presence or addition of further features in various embodiments of the invention. In the present application the term "<com:Math><semantics>C1−20<annotation encoding="application / x-tex">C_{1-20}< / annotation>< / semantics>< / com:Math>" alkyl refers to a straight or branched fully saturated hydrocarbon group having from 1 to 20 carbon atoms. The term encompasses methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, s-butyl and t-butyl. Other alkyl groups, for example <com:Math><semantics>C1−12<annotation encoding="application / x-tex">C_{1-12}< / annotation>< / semantics>< / com:Math> alkyl, <com:Math><semantics>C1−10<annotation encoding="application / x-tex">C_{1-10}< / annotation>< / semantics>< / com:Math> alkyl, <com:Math><semantics>C1−8<annotation encoding="application / x-tex">C_{1-8}< / annotation>< / semantics>< / com:Math> alkyl, <com:Math><semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics>< / com:Math> alkyl, <com:Math><semantics>C1−5<annotation encoding="application / x-tex">C_{1-5}< / annotation>< / semantics>< / com:Math> alkyl, <com:Math><semantics>C1−4<annotation encoding="application / x-tex">C_{1-4}< / annotation>< / semantics>< / com:Math> alkyl, <com:Math><semantics>C1−3<annotation encoding="application / x-tex">C_{1-3}< / annotation>< / semantics>< / com:Math> alkyl, or C<com:Sub>1-2< / com:Sub> alkyl are as defined above but contain different numbers of carbon atoms. The terms "heterocyclic" and "heterocyclyl" refer to a non-aromatic cyclic group having 3 to 10 ring atoms and at least one heteroatom selected from N, O, S and B and optionally substituted with one or more =O moieties. Examples of heterocyclic groups include pyrrolidine, piperidine, morpholine, piperazine, tetrahydrofuran, dioxolane (e.g. 1,3- dioxolane), dioxane (e.g. 1,3-dioxane) and cyclic thioethers. The term also includes bicyclic and bridged groups such as 9-borabicyclo(3.3.1)nonane (9-BBN). The term "halogen" refers to fluorine, chlorine, bromine or iodine and the term "halo" to fluoro, chloro, bromo or iodo groups. The term "C<com:Sub>1-6< / com:Sub> haloalkyl" refers to a straight or branched alkyl group as defined above having from 1 to 6 carbon atoms and substituted with one or more halo atoms, up to perhalo substitution. Examples include trifluoromethyl, chloroethyl and 1,1-difluoroethyl. Other haloalkyl groups, for example C<com:Sub>1-5< / com:Sub> haloalkyl, C<com:Sub>1-4< / com:Sub> haloalkyl, C<com:Sub>1-3< / com:Sub> haloalkyl or C<com:Sub>1-2< / com:Sub> haloalkyl are as defined above but contain different numbers of carbon atoms. The term "C<com:Sub>2-20< / com:Sub> alkenyl" refers to a straight or branched hydrocarbon group having from 2 to 20 carbon atoms and at least one carbon-carbon double bond. Examples include ethenyl (vinyl), prop-1-enyl, prop-2-enyl (allyl), hex-2-enyl etc. Other alkenyl groups, for example C<com:Sub>2-12< / com:Sub> alkenyl, C<com:Sub>2-10< / com:Sub> alkenyl, C<com:Sub>2-8< / com:Sub> alkenyl, C<com:Sub>2-6< / com:Sub> alkenyl, C<com:Sub>2-5< / com:Sub> alkenyl, C<com:Sub>2-4< / com:Sub> alkenyl or <com:Math><semantics>C2−3<annotation encoding="application / x-tex">C_{2-3}< / annotation>< / semantics>< / com:Math> alkenyl are as defined above but contain different numbers of carbon atoms. The term "C<com:Sub>2-20< / com:Sub> alkynyl" refers to a straight or branched hydrocarbon group having from 2 to 20 carbon atoms and at least one carbon-carbon triple bond. Examples include ethynyl, prop-1-ynyl, hex-2-ynyl etc. Other alkynyl groups, for example <com:Math><semantics>C2−12<annotation encoding="application / x-tex">C_{2-12}< / annotation>< / semantics>< / com:Math> alkynyl, <com:Math><semantics>C2−10<annotation encoding="application / x-tex">C_{2-10}< / annotation>< / semantics>< / com:Math> alkynyl, C<com:Sub>2-8< / com:Sub> alkynyl, C<com:Sub>2-6< / com:Sub> alkynyl, C<com:Sub>2-5< / com:Sub> alkynyl, C<com:Sub>2-4< / com:Sub> alkynyl or C<com:Sub>2-3< / com:Sub> alkynyl are as defined above but contain different numbers of carbon atoms. The term "alkylene" refers to a straight or branched fully saturated hydrocarbon chain. Suitably alkylene is C<com:Sub>1-20< / com:Sub> alkylene, C<com:Sub>1-12< / com:Sub> alkylene, C<com:Sub>1-10< / com:Sub> alkylene, C<com:Sub>1-8< / com:Sub> alkylene, C<com:Sub>1-6< / com:Sub> alkylene, C<com:Sub>1-5< / com:Sub> alkylene, C<com:Sub>1-4< / com:Sub> alkylene, C<com:Sub>1-3< / com:Sub> alkylene, or C<com:Sub>1-2< / com:Sub> alkylene. Examples of alkylene groups include -CH<com:Sub>2< / com:Sub>-, -CH<com:Sub>2< / com:Sub>CH<com:Sub>2< / com:Sub>-, -CH(CH<com:Sub>3< / com:Sub>)-CH<com:Sub>2< / com:Sub>-, -CH<com:Sub>2< / com:Sub>CH(CH<com:Sub>3< / com:Sub>)-, -CH<com:Sub>2< / com:Sub>CH<com:Sub>2< / com:Sub>CH<com:Sub>2< / com:Sub>-, -CH<com:Sub>2< / com:Sub>CH(CH<com:Sub>2< / com:Sub>CH<com:Sub>3< / com:Sub>)- and -CH<com:Sub>2< / com:Sub>CH(CH<com:Sub>2< / com:Sub>CH<com:Sub>3< / com:Sub>)CH<com:Sub>2< / com:Sub>-. The term "alkenylene" refers to a straight or branched hydrocarbon chain containing at least one carbon-carbon double bond. Suitably alkenylene is <com:Math><semantics>C2−20<annotation encoding="application / x-tex">C_{2-20}< / annotation>< / semantics>< / com:Math> alkenylene, <com:Math><semantics>C2−12<annotation encoding="application / x-tex">C_{2-12}< / annotation>< / semantics>< / com:Math> alkenylene, <com:Math><semantics>C2−10<annotation encoding="application / x-tex">C_{2-10}< / annotation>< / semantics>< / com:Math> alkenylene, <com:Math><semantics>C2−8<annotation encoding="application / x-tex">C_{2-8}< / annotation>< / semantics>< / com:Math> alkenylene, <com:Math><semantics>C2−6<annotation encoding="application / x-tex">C_{2-6}< / annotation>< / semantics>< / com:Math> alkenylene, <com:Math><semantics>C2−5<annotation encoding="application / x-tex">C_{2-5}< / annotation>< / semantics>< / com:Math> alkenylene, <com:Math><semantics>C2−4<annotation encoding="application / x-tex">C_{2-4}< / annotation>< / semantics>< / com:Math> alkenylene, or C<com:Sub>2-3< / com:Sub> alkenylene. Examples of alkenylene groups include -CH=CH-, -CH=C(CH<com:Sub>3< / com:Sub>)-, -CH<com:Sub>2< / com:Sub>CH=CH-, -CH=CHCH<com:Sub>2< / com:Sub>-, -CH<com:Sub>2< / com:Sub>CH<com:Sub>2< / com:Sub>CH=CH-, [Image disponible dans le document PDF, Image available in the PDF document] The term "C<com:Sub>2-20< / com:Sub> alkynyl" refers to a straight or branched hydrocarbon group having from 2 to 20 carbon atoms and at least one carbon-carbon triple bond. Examples include ethynyl, prop-1-ynyl, hex-2-ynyl etc. Other alkynyl groups, for example C<com:Sub>2-12< / com:Sub> alkynyl, C<com:Sub>2-10< / com:Sub> alkynyl, <com:Math><semantics>C2−8<annotation encoding="application / x-tex">C_{2-8}< / annotation>< / semantics>< / com:Math> alkynyl, <com:Math><semantics>C2−6<annotation encoding="application / x-tex">C_{2-6}< / annotation>< / semantics>< / com:Math> alkynyl, <com:Math><semantics>C2−5<annotation encoding="application / x-tex">C_{2-5}< / annotation>< / semantics>< / com:Math> alkynyl, <com:Math><semantics>C2−4<annotation encoding="application / x-tex">C_{2-4}< / annotation>< / semantics>< / com:Math> alkynyl or <com:Math><semantics>C2−3<annotation encoding="application / x-tex">C_{2-3}< / annotation>< / semantics>< / com:Math> alkynyl are as defined above but contain different numbers of carbon atoms. The term "alkyl" refers to a straight or branched fully saturated hydrocarbon chain. Suitably alkylene is <com:Math><semantics>C1−20<annotation encoding="application / x-tex">C_{1-20}< / annotation>< / semantics>< / com:Math> alkyl, <com:Math><semantics>C1−12<annotation encoding="application / x-tex">C_{1-12}< / annotation>< / semantics>< / com:Math> alkyl, <com:Math><semantics>C1−10<annotation encoding="application / x-tex">C_{1-10}< / annotation>< / semantics>< / com:Math> alkyl, <com:Math><semantics>C1−8<annotation encoding="application / x-tex">C_{1-8}< / annotation>< / semantics>< / com:Math> alkyl, <com:Math><semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics>< / com:Math> alkyl, <com:Math><semantics>C1−5<annotation encoding="application / x-tex">C_{1-5}< / annotation>< / semantics>< / com:Math> alkyl, <com:Math><semantics>C1−4<annotation encoding="application / x-tex">C_{1-4}< / annotation>< / semantics>< / com:Math> alkyl, <com:Math><semantics>C1−3<annotation encoding="application / x-tex">C_{1-3}< / annotation>< / semantics>< / com:Math> alkyl, or C<com:Sub>1-2< / com:Sub> alkyl. Examples of alkyl groups include -CH<com:Sub>3< / com:Sub>, -CH<com:Sub>2< / com:Sub>CH<com:Sub>3< / com:Sub>, -CH(CH<com:Sub>3< / com:Sub>)-CH<com:Sub>3< / com:Sub>, - <com:Math><semantics>CH2CH2CH3<annotation encoding="application / x-tex">CH_2CH_2CH_3< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−C(CH3)3<annotation encoding="application / x-tex">-C(CH_3)_3< / annotation>< / semantics>< / com:Math> and <com:Math><semantics>−CH2CH2CH2CH3<annotation encoding="application / x-tex">-CH_2CH_2CH_2CH_3< / annotation>< / semantics>< / com:Math>. The term "alkenyl" refers to a straight or branched hydrocarbon chain containing at least one carbon-carbon double bond. Suitably alkenyl is C<com:Sub>2-20< / com:Sub> alkenyl, C<com:Sub>2-12< / com:Sub> alkenyl, C<com:Sub>2-10< / com:Sub> alkenyl, C<com:Sub>2-8< / com:Sub> alkenyl, C<com:Sub>2-6< / com:Sub> alkenyl, C<com:Sub>2-5< / com:Sub> alkenyl, C<com:Sub>2-4< / com:Sub> alkenyl, or C<com:Sub>2-3< / com:Sub> alkenyl. Examples of alkenyl groups include -CH=CH<com:Sub>2< / com:Sub>, -CH=CH(CH<com:Sub>3< / com:Sub>), -CH<com:Sub>2< / com:Sub>CH=CH<com:Sub>2< / com:Sub>, -CH=CHCH<com:Sub>3< / com:Sub>, - <com:Math><semantics>CH2CH2CH=CH2<annotation encoding="application / x-tex">CH_2CH_2CH=CH_2< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−CH2CH=CH(CH3)<annotation encoding="application / x-tex">-CH_2CH=CH(CH_3)< / annotation>< / semantics>< / com:Math>- and <com:Math><semantics>−CH2CH=CH(CH2CH3)<annotation encoding="application / x-tex">-CH_2CH=CH(CH_2CH_3)< / annotation>< / semantics>< / com:Math>. The term "alkynylene" refers to a straight or branched hydrocarbon chain containing at least one carbon-carbon triple bond. Suitably alkynylene is C<com:Sub>2-20< / com:Sub> alkynylene, C<com:Sub>2-12< / com:Sub> alkynylene, C<com:Sub>2-10< / com:Sub> alkynylene, C<com:Sub>2-8< / com:Sub> alkynylene, C<com:Sub>2-6< / com:Sub> alkynylene, C<com:Sub>2-5< / com:Sub> alkynylene, C<com:Sub>2-4< / com:Sub> alkynylene, or C<com:Sub>2-3< / com:Sub> alkynylene. Examples of alkynylene groups include -C<com:Math><semantics>≡<annotation encoding="application / x-tex">\equiv< / annotation>< / semantics>< / com:Math>C-, -CH<com:Sub>2< / com:Sub>C<com:Math><semantics>≡<annotation encoding="application / x-tex">\equiv< / annotation>< / semantics>< / com:Math>C-, -C<com:Math><semantics>≡<annotation encoding="application / x-tex">\equiv< / annotation>< / semantics>< / com:Math>C-CH<com:Sub>2< / com:Sub>-, -CH<com:Sub>2< / com:Sub>CC<com:Math><semantics>≡<annotation encoding="application / x-tex">\equiv< / annotation>< / semantics>< / com:Math>C-, -CH<com:Sub>2< / com:Sub>C<com:Math><semantics>≡<annotation encoding="application / x-tex">\equiv< / annotation>< / semantics>< / com:Math>CCH<com:Sub>2< / com:Sub>- and -CH<com:Sub>2< / com:Sub>C<com:Math><semantics>≡<annotation encoding="application / x-tex">\equiv< / annotation>< / semantics>< / com:Math>C-CH<com:Sub>2< / com:Sub>CH<com:Sub>2< / com:Sub>-. The terms "aryl" and "aromatic" refer to a cyclic group with aromatic character having from 6 to 14 ring carbon atoms (unless otherwise specified, for example 6 to 10 ring carbon atoms) and containing up to three rings. Where an aryl group contains more than one ring, not all rings must be aromatic in character. Examples include phenyl, naphthyl and anthracenyl as well as partially saturated systems such as tetrahydronaphthyl, indanyl and indenyl. A further example of an aryl group is 1,2,3,4-tetrahydronaphthalene. The terms "heteroaryl" and "heteroaromatic" refer to a cyclic group with aromatic character having from 5 to 14 ring atoms (unless otherwise specified, for example 5 to 10 ring atoms), at least one of which is a heteroatom selected from N, O and S, and containing up to three rings. Where a heteroaryl group contains more than one ring, not all rings must be aromatic in character. Examples of heteroaryl groups include pyridine, pyrimidine, indole, benzofuran, benzimidazole and indolene. Further examples of heteroaryl groups include quinoline and isoquinoline. The term "isotopic variant" refers to isotopically-labelled compounds which are identical to those recited in formula (Ia) or formula (I) but for the fact that one or more atoms are replaced by an atom having an atomic mass or mass number different from the atomic mass or mass number most commonly found in nature, or in which the proportion of an atom having an atomic mass or mass number found less commonly in nature has been increased (the latter concept being referred to as "isotopic enrichment"). Examples of isotopes that can be incorporated into compounds of the invention include isotopes of hydrogen, carbon, nitrogen, oxygen, fluorine, iodine and chlorine such as <com:Sup>2< / com:Sup>H (deuterium), <com:Sup>3< / com:Sup>H, <com:Sup>11< / com:Sup>C, <com:Sup>13< / com:Sup>C, <com:Sup>14< / com:Sup>C, <com:Sup>18< / com:Sup>F, <com:Sup>123< / com:Sup>I or <com:Sup>125< / com:Sup>I (e.g. <com:Sup>3< / com:Sup>H, <com:Sup>11< / com:Sup>C, <com:Sup>14< / com:Sup>C, <com:Sup>18< / com:Sup>F, <com:Sup>123< / com:Sup>I or <com:Sup>125< / com:Sup>I), which may be naturally occurring or non-naturally occurring isotopes. Polyethylene glycol (PEG) is a polyether compound, which in linear form has general formula H-[O-CH<com:Sub>2< / com:Sub>-CH<com:Sub>2< / com:Sub>]<com:Sub>n< / com:Sub>-OH. A polyethylene glycol residue is a PEG in which the terminal H is replaced by a bond linking it to the remainder of the molecule. Branched versions, including hyperbranched and dendritic versions are also contemplated and are generally known in the art. Typically, a branched polymer has a central branch core moiety and a plurality of linear polymer chains linked to the central branch core. PEG is commonly used in branched forms that can be prepared by addition of ethylene oxide to various polyols, such as glycerol, glycerol oligomers, pentaerythritol and sorbitol. The central branch moiety can also be derived from several amino acids, such as lysine. The branched poly (ethylene glycol) can be represented in general form as R(-PEG-OH)<com:Sub>m< / com:Sub> in which R is derived from a core moiety, such as glycerol, glycerol oligomers, or pentaerythritol, and m represents the number of arms. Multi-armed PEG molecules, such as those described in US5,932,462; US5,643,575; US5,229,490; US4,289,872; US2003 / 0143596; WO96 / 21469; and WO93 / 21259 may also be used. The PEG polymers may have an average molecular weight of, for example, 600-2,000,000 Da, 60,000-2,000,000 Da, 40,000-2,000,000 Da, 400,000-1,600,000 Da, 800-1,200,000 Da, 600-40,000 Da, 600-20,000 Da, 4,000-16,000 Da, or 8,000-12,000 Da. The term "protected OH" relates to an OH group protected with any suitable protecting group. For example, the protected OH may be a group R<com:Sup>4< / com:Sup> as defined above. Suitable protecting groups include esters such that, for example when R<com:Sup>2< / com:Sup> and / or R<com:Sup>5< / com:Sup> and / or R<com:Sup>3< / com:Sup> is a protected OH group, R<com:Sup>2< / com:Sup> and / or R<com:Sup>5< / com:Sup> and / or R<com:Sup>3< / com:Sup> may independently be a group OC(O)R<com:Sup>14< / com:Sup>, where R<com:Sup>14< / com:Sup> is a group R<com:Sup>10< / com:Sup> as defined above. Silyl ethers are also suitable, and in this case, R<com:Sup>2< / com:Sup> and / or R<com:Sup>5< / com:Sup> and / or R<com:Sup>3< / com:Sup> may independently be a group OSi(R<com:Sup>16< / com:Sup>)<com:Sub>3< / com:Sub>, where each R<com:Sup>16< / com:Sup> is independently a group R<com:Sup>13< / com:Sup> as defined above. Other suitable protecting groups for OH are well known to those of skill in the art (see Wuts, PGM and Greene, TW (2006) "Greene's Protective Groups in Organic Synthesis", 4th Edition, John Wiley & Sons, Inc., Hoboken, NJ, USA). Salts of the compounds of general formula (XVIIIa) and (XVIII) are suitably pharmaceutically or veterinarily acceptable salts. Salts which are not pharmaceutically or veterinarily acceptable may still be valuable as intermediates. References to a protecting group which is stable in basic conditions mean that the protecting group cannot be removed by treatment with a base. Appropriate salts of the compounds described herein include basic addition salts such as sodium, potassium, calcium, aluminium, zinc, magnesium and other metal salts as well as choline, diethanolamine, ethanolamine, ethyl diamine, meglumine and other well-known basic addition salts as summarised in Paulekuhn et al., J. Med. Chem. 2007, 50, 6665- 6672 and / or known to those skilled in the art. The term "carboxylic acid mimetic group" relates to known carboxylic acid isosteres including tetrazole, substituted tetrazole, -SO<com:Sub>2< / com:Sub>-NHR<com:Sup>10< / com:Sup>, C(O)NH-SO<com:Sub>2< / com:Sub>R<com:Sup>10< / com:Sup> and NHC(O)NH- SO<com:Sub>2< / com:Sub>R<com:Sup>10< / com:Sup>; wherein R<com:Sup>10< / com:Sup> is as above defined for a compound of general formulae (la) or (l) and is suitably H, C<com:Sub>1-6< / com:Sub> alkyl, C<com:Sub>3-7< / com:Sub> cycloalkyl or 6- to 14- membered aryl (e.g. phenyl). Tetrazole groups include tetrazole-5-yl and tetrazole-1-yl. Substituted tetrazole includes tetrazole substituted with C<com:Sub>1-4< / com:Sub> alkyl, halo, OH, O(C<com:Sub>1-4< / com:Sub> alkyl) or SO<com:Sub>2< / com:Sub>R<com:Sup>10< / com:Sup> (e.g. SO<com:Sub>2< / com:Sub>(C<com:Sub>1-4< / com:Sub> alkyl), SO<com:Sub>2< / com:Sub>-phenyl or SO<com:Sub>2< / com:Sub>-tolyl). Such carboxylic acid mimetic groups are well known in the art and are discussed, for example in "On Medicinal Chemistry"; M Stocks, L Alcaraz, E Griffen; Pub: Sci-ink Ltd (April 2007). Particularly suitable carboxylic acid mimetic groups include tetrazole, C(O)NH-SO<com:Sub>2< / com:Sub>R<com:Sup>10< / com:Sup> and NHC(O)NH-SO<com:Sub>2< / com:Sub>R<com:Sup>10< / com:Sup>, with tetrazole being particularly suitable. In one aspect of the invention is provided a compound of general formula (la): [Image disponible dans le document PDF, Image available in the PDF document] (la) wherein Y, R<com:Sup>2< / com:Sup>, R<com:Sup>4< / com:Sup> and R<com:Sup>5< / com:Sup> are as above defined. Suitably, the compound of general formula (la) is: [Image disponible dans le document PDF, Image available in the PDF document] (la) wherein Y, R<com:Sup>2< / com:Sup>, R<com:Sup>4< / com:Sup> and R<com:Sup>5< / com:Sup> are as above defined. In one embodiment, the compound of formula (la) is: [Image disponible dans le document PDF, Image available in the PDF document] In one embodiment, the compound of formula (la) is: [Image disponible dans le document PDF, Image available in the PDF document] In one embodiment, the compound of formula (Ia) is not: [Image disponible dans le document PDF, Image available in the PDF document] ٠ In one embodiment, the compound of formula (Ia) is not: [Image disponible dans le document PDF, Image available in the PDF document] In one aspect of the invention is provided a compound of general formula (I): [Image disponible dans le document PDF, Image available in the PDF document] (l) wherein Y, R<com:Sup>2< / com:Sup>, R<com:Sup>4< / com:Sup> and R<com:Sup>5< / com:Sup> are as above defined. Suitably, the compound of general formula (I) is: [Image disponible dans le document PDF, Image available in the PDF document] (1) wherein Y, R<com:Sup>2< / com:Sup>, R<com:Sup>4< / com:Sup> and R<com:Sup>5< / com:Sup> are as above defined. In one embodiment, the compound of formula (I) is not: [Image disponible dans le document PDF, Image available in the PDF document] ٠ In one embodiment, the compound of formula (I) is not: [Image disponible dans le document PDF, Image available in the PDF document] In another aspect of the invention is provided a compound of general formula (IIIxa): [Image disponible dans le document PDF, Image available in the PDF document] (IIIxa) or a salt an isotopic variant thereof, wherein X is CI, Br or I; and wherein Y, R<com:Sup>2< / com:Sup>, R<com:Sup>4< / com:Sup> and R<com:Sup>5< / com:Sup> are as above defined for a compound of general formula (Ia). Suitably, the compound of general formula (IIIxa) is: [Image disponible dans le document PDF, Image available in the PDF document] (IIIxa) or a salt an isotopic variant thereof, wherein X is CI, Br or I; and wherein Y, R<com:Sup>2< / com:Sup>, R<com:Sup>4< / com:Sup> and R<com:Sup>5< / com:Sup> are as above defined for a compound of general formula (Ia). In another aspect of the invention is provided a compound of general formula (IIIx): [Image disponible dans le document PDF, Image available in the PDF document] (IIIX) or a salt an isotopic variant thereof, wherein X is CI, Br or I; and wherein Y, R<com:Sup>2< / com:Sup>, R<com:Sup>4< / com:Sup> and R<com:Sup>5< / com:Sup> are as above defined for a compound of general formula (I). Suitably, the compound of general formula (IIIIx) is: [Image disponible dans le document PDF, Image available in the PDF document] (IIIX) or a salt an isotopic variant thereof, wherein X is CI, Br or I; and wherein Y, R<com:Sup>2< / com:Sup>, R<com:Sup>4< / com:Sup> and R<com:Sup>5< / com:Sup> are as above defined for a compound of general formula (I). In another aspect of the invention is provided a compound of general formula (IIIya): [Image disponible dans le document PDF, Image available in the PDF document] (Illya) or a salt or an isotopic variant thereof, wherein X is CI, Br or I; and wherein Y, R<com:Sup>2< / com:Sup>, R<com:Sup>4< / com:Sup> and R<com:Sup>5< / com:Sup> are as above defined for a compound of general formula (Ia). Suitably, the compound of general formula (IIIya) is: [Image disponible dans le document PDF, Image available in the PDF document] (IIIya) or a salt or an isotopic variant thereof, wherein X is CI, Br or I; and wherein Y, R<com:Sup>2< / com:Sup>, R<com:Sup>4< / com:Sup> and R<com:Sup>5< / com:Sup> are as above defined for a compound of general formula (Ia). In another aspect of the invention is provided a compound of general formula (IIIy): [Image disponible dans le document PDF, Image available in the PDF document] (IIIy) or a salt or an isotopic variant thereof, wherein X is Cl, Br or I; and wherein Y, R<com:Sup>2< / com:Sup>, R<com:Sup>4< / com:Sup> and R<com:Sup>5< / com:Sup> are as above defined for a compound of general formula (I). Suitably, the compound of general formula (IIIy) is: [Image disponible dans le document PDF, Image available in the PDF document] (IIIy) or a salt or an isotopic variant thereof, wherein X is Cl, Br or I; and wherein Y, R<com:Sup>2< / com:Sup>, R<com:Sup>4< / com:Sup> and R<com:Sup>5< / com:Sup> are as above defined for a compound of general formula (I). In a further aspect of the invention is provided a compound of general formula (IVa): [Image disponible dans le document PDF, Image available in the PDF document] (IVa) or a salt an isotopic variant thereof, wherein R<com:Sup>1< / com:Sup> is as defined for a compound of formula (Xa); and Y, R<com:Sup>2< / com:Sup>, R<com:Sup>4< / com:Sup> and R<com:Sup>5< / com:Sup> are as defined for compounds of general formula (la). Suitably the compound of general formula (IVa) is: [Image disponible dans le document PDF, Image available in the PDF document] (IVa) or a salt an isotopic variant thereof, wherein R<com:Sup>1< / com:Sup> is as defined for a compound of formula (Xa); and Y, R<com:Sup>2< / com:Sup>, R<com:Sup>4< / com:Sup> and R<com:Sup>5< / com:Sup> are as defined for compounds of general formula (la). Suitably the compound of general formula (IVa) is: [Image disponible dans le document PDF, Image available in the PDF document] (IVa) or a salt an isotopic variant thereof, wherein R<com:Sup>1< / com:Sup> is as defined for a compound of formula (Xa); and Y, R<com:Sup>2< / com:Sup>, R<com:Sup>4< / com:Sup> and R<com:Sup>5< / com:Sup> are as defined for compounds of general formula (la). Suitably the compound of general formula (IVa) is: [Image disponible dans le document PDF, Image available in the PDF document] (IVa) or a salt an isotopic variant thereof, wherein R<com:Sup>1< / com:Sup> is as defined for a compound of formula (Xa); and Y, R<com:Sup>2< / com:Sup>, R<com:Sup>4< / com:Sup> and R<com:Sup>5< / com:Sup> are as defined for compounds of general formula (la). In a further aspect of the invention is provided a compound of general formula (IV): [Image disponible dans le document PDF, Image available in the PDF document] (IV) or a salt an isotopic variant thereof, wherein R<com:Sup>1< / com:Sup> is as defined for a compound of formula (X); and Y, R<com:Sup>2< / com:Sup>, R<com:Sup>4< / com:Sup> and R<com:Sup>5< / com:Sup> are as defined for compounds of general formula (I). Suitably the compound of general formula (IV) is: [Image disponible dans le document PDF, Image available in the PDF document] (IV) or a salt an isotopic variant thereof, wherein R<com:Sup>1< / com:Sup> is as defined for a compound of formula (X); and Y, R<com:Sup>2< / com:Sup>, R<com:Sup>4< / com:Sup> and R<com:Sup>5< / com:Sup> are as defined for compounds of general formula (I). Suitably the compound of general formula (IV) is: [Image disponible dans le document PDF, Image available in the PDF document] (IV) or a salt an isotopic variant thereof, wherein R<com:Sup>1< / com:Sup> is as defined for a compound of formula (X); and Y, R<com:Sup>2< / com:Sup>, R<com:Sup>4< / com:Sup> and R<com:Sup>5< / com:Sup> are as defined for compounds of general formula (I). Suitably the compound of general formula (IV) is: [Image disponible dans le document PDF, Image available in the PDF document] (IV) or a salt an isotopic variant thereof, wherein R<com:Sup>1< / com:Sup> is as defined for a compound of formula (Xa); and Y, R<com:Sup>2< / com:Sup>, R<com:Sup>4< / com:Sup> and R<com:Sup>5< / com:Sup> are as defined for compounds of general formula (I). In a further aspect of the invention is provided a compound of general formula (Va): [Image disponible dans le document PDF, Image available in the PDF document] (Va) or a salt an isotopic variant thereof, wherein Y<com:Sup>1< / com:Sup> and R<com:Sup>1< / com:Sup> are as above defined for compounds of general formula (Xa); and R<com:Sup>2< / com:Sup>, R<com:Sup>4< / com:Sup> and R<com:Sup>5< / com:Sup> are as defined for compounds of general formula (Ia). In a further aspect of the invention is provided a compound of general formula (V): [Image disponible dans le document PDF, Image available in the PDF document] (V) or a salt an isotopic variant thereof, wherein Y<com:Sup>1< / com:Sup> and R<com:Sup>1< / com:Sup> are as above defined for compounds of general formula (X); and R<com:Sup>2< / com:Sup>, R<com:Sup>4< / com:Sup> and R<com:Sup>5< / com:Sup> are as defined for compounds of general formula (I). In one aspect of the invention is provided a compound of general formula (IIIxz): [Image disponible dans le document PDF, Image available in the PDF document] (IIIxz) or a salt an isotopic variant thereof, wherein X is CI, Br or I; wherein R<com:Sup>40< / com:Sup> is C(O)H, C(O)C<com:Sub>1-4< / com:Sub> alkyl, C(O)phenyl, C(O)benzyl, phenyl, benzyl, C<com:Sub>2-4< / com:Sub> alkenyl or SO<com:Sub>2< / com:Sub>CF<com:Sub>3< / com:Sub>; wherein C(O)phenyl, C(O)benzyl, phenyl and benzyl are optionally substituted with one or more substituents selected from C<com:Sub>1-4< / com:Sub> alkyl, OC<com:Sub>1-4< / com:Sub> alkyl, halo, nitro, C<com:Sub>1-4< / com:Sub> haloalkyl and OC<com:Sub>1-4< / com:Sub> haloalkyl; and wherein Y, R<com:Sup>2< / com:Sup>, R<com:Sup>4< / com:Sup> and R<com:Sup>5< / com:Sup> are as above defined for a compound of general formula (la). Suitably, the compound of general formula (IIIIxz) is: [Image disponible dans le document PDF, Image available in the PDF document] (IIIxz) or a salt an isotopic variant thereof, wherein X is CI, Br or I; wherein R<com:Sup>40< / com:Sup> is C(O)H, C(O)C<com:Sub>1-4< / com:Sub> alkyl, C(O)phenyl, C(O)benzyl, phenyl, benzyl, C<com:Sub>2-4< / com:Sub> alkenyl or SO<com:Sub>2< / com:Sub>CF<com:Sub>3< / com:Sub>; wherein C(O)phenyl, C(O)benzyl, phenyl and benzyl are optionally substituted with one or more substituents selected from C<com:Sub>1-4< / com:Sub> alkyl, OC<com:Sub>1-4< / com:Sub> alkyl, halo, nitro, C<com:Sub>1-4< / com:Sub> haloalkyl and OC<com:Sub>1-4< / com:Sub> haloalkyl; and wherein Y, R<com:Sup>2< / com:Sup>, R<com:Sup>4< / com:Sup> and R<com:Sup>5< / com:Sup> are as above defined for a compound of general formula (la). In another aspect of the invention is provided a compound of general formula (IIIyz): [Image disponible dans le document PDF, Image available in the PDF document] (IIIyz) or a salt or an isotopic variant thereof, wherein X is CI, Br or I; wherein R<com:Sup>40< / com:Sup> is C(O)H, C(O)C<com:Sub>1-4< / com:Sub> alkyl, C(O)phenyl, C(O)benzyl, phenyl, benzyl, C<com:Sub>2-4< / com:Sub> alkenyl or SO<com:Sub>2< / com:Sub>CF<com:Sub>3< / com:Sub>; wherein C(O)phenyl, C(O)benzyl, phenyl and benzyl are optionally substituted with one or more substituents selected from C<com:Sub>1-4< / com:Sub> alkyl, OC<com:Sub>1-4< / com:Sub> alkyl, halo, nitro, C<com:Sub>1-4< / com:Sub> haloalkyl and OC<com:Sub>1-4< / com:Sub> haloalkyl; and wherein Y, R<com:Sup>2< / com:Sup>, R<com:Sup>4< / com:Sup> and R<com:Sup>5< / com:Sup> are as above defined for a compound of general formula (la). Suitably, the compound of general formula (IIIyz) is: [Image disponible dans le document PDF, Image available in the PDF document] (IIIyz) or a salt or an isotopic variant thereof, wherein X is Cl, Br or I; wherein R<com:Sup>40< / com:Sup> is C(O)H, C(O)C<com:Sub>1-4< / com:Sub> alkyl, C(O)phenyl, C(O)benzyl, phenyl, benzyl, C<com:Sub>2-4< / com:Sub> alkenyl or SO<com:Sub>2< / com:Sub>CF<com:Sub>3< / com:Sub>; wherein C(O)phenyl, C(O)benzyl, phenyl and benzyl are optionally substituted with one or more substituents selected from C<com:Sub>1-4< / com:Sub> alkyl, OC<com:Sub>1-4< / com:Sub> alkyl, halo, nitro, C<com:Sub>1-4< / com:Sub> haloalkyl and OC<com:Sub>1-4< / com:Sub> haloalkyl; and wherein Y, R<com:Sup>2< / com:Sup>, R<com:Sup>4< / com:Sup> and R<com:Sup>5< / com:Sup> are as above defined for a compound of general formula (la). In one embodiment is provided a mixture of a compound of general formula (IIIxz) and a compound of general formula (IIIyz). In one embodiment is provided a mixture comprising a compound of general formula (IIIxz) and a compound of general formula (IIIyz). The following embodiments relate to compounds of general formulae (la), (l), (lla), (ll), (IIIxa), (IIIx), (IIIya), (IIIy), (IIIxz), (IIIyz), (IVa), (IV), (Va), (V), (Vla), (VI), (Xa) and (X) where applicable, and to methods and intermediates for their preparation as described herein, unless otherwise stated. Embodiments relating to individual R groups, Y groups and X groups are envisaged as being fully combinable with one or more other R groups to form further embodiments of the invention. In one embodiment, R<com:Sup>2< / com:Sup> is H. In one embodiment, R<com:Sup>2< / com:Sup> is halo. In one embodiment, R<com:Sup>2< / com:Sup> is OH. In one embodiment, R<com:Sup>2< / com:Sup> is a protected OH group. In one embodiment, R<com:Sup>2< / com:Sup> is a protected OH group which is not stable in a basic environment such that treatment with a base converts the protected OH group to OH. Examples of such groups are well known in the art and include a group OC(O)R<com:Sup>14< / com:Sup>, wherein R<com:Sup>14< / com:Sup> is a group R<com:Sup>10< / com:Sup> as defined above for general formula (I), and is suitably C<com:Sub>1-6< / com:Sub> alkyl or benzyl, or C<com:Sub>1-6< / com:Sub> alkyl or phenyl. In another embodiment, R<com:Sup>2< / com:Sup> is a protected OH group which is stable in a basic environment. Examples of such groups include OSi(R<com:Sup>16< / com:Sup>)<com:Sub>3< / com:Sub>, where each R<com:Sup>16< / com:Sup> is independently a group R<com:Sup>13< / com:Sup> as defined above for general formula (I) and general formula (Ia), and is suitably C<com:Sub>1-6< / com:Sub> alkyl or phenyl. In one embodiment, Si(R<com:Sup>16< / com:Sup>)<com:Sub>3< / com:Sub> is selected from the group consisting of trimethylsilyl (TMS), triethylsilyl (TES), triphenylsilyl (TPS), tri-isopropylsilyl (TIPS), thexyldimethylsilyl (TDS), tert-butyldiphenylsilyl (TBDPS), tert-butyldimethylsilyl (TBDMS or TBS), di-tert- butylmethylsilyl (DTBMS), diethylisopropylsilyl (DEIPS) and dimethylisopropylsilyl (DMIPS), in particular TMS, TES, TIPS, TBDMS and TBDPS. In one embodiment, R<com:Sup>2< / com:Sup> is in the "up" position i.e. is in the beta-configuration. In one embodiment, Y is a bond. In one embodiment, for compounds of general formulae (Ia), (I), (IIa), (II), (IIIxa), (IIIx), (IIIya), (IIIy), (IIIxz), (IIIyz), (IVa) and (IV) Y is a C<com:Sub>1-20< / com:Sub>, C<com:Sub>1-12< / com:Sub>, C<com:Sub>1-10< / com:Sub>, C<com:Sub>1-8< / com:Sub>, C<com:Sub>1-6< / com:Sub>, C<com:Sub>1-5< / com:Sub>, C<com:Sub>1-4< / com:Sub>, C<com:Sub>1-3< / com:Sub> or C<com:Sub>1-2< / com:Sub> alkylene or a C<com:Sub>2-12< / com:Sub>, C<com:Sub>2-10< / com:Sub>, C<com:Sub>2-8< / com:Sub>, C<com:Sub>2-6< / com:Sub>, C<com:Sub>2-5< / com:Sub>, C<com:Sub>2-4< / com:Sub>, C<com:Sub>2-3< / com:Sub> or C<com:Sub>2< / com:Sub> alkenylene linker group either of which is optionally substituted with one or more groups R<com:Sup>3< / com:Sup> as defined above. In one embodiment, for compounds of general formulae (Va), (V), (Vla), (Vl), (Xa) and (X) Y is a C<com:Sub>1-20< / com:Sub>, C<com:Sub>1-12< / com:Sub>, C<com:Sub>1-10< / com:Sub>, C<com:Sub>1-8< / com:Sub>, C<com:Sub>1-6< / com:Sub>, C<com:Sub>1-5< / com:Sub>, C<com:Sub>1-4< / com:Sub>, C<com:Sub>1-3< / com:Sub> or C<com:Sub>1-2< / com:Sub> alkylene linker group which is optionally substituted with one or more groups R<com:Sup>3< / com:Sup> as defined above. In one embodiment, for compounds of general formulae (Ia), (I), (IIa), (II), (IIIxa), (IIIx), (IIIya), (IIIy), (IIIxz), (IIIyz), (IVa) and (IV) Y is bond, or a C<com:Sub>1-3< / com:Sub> alkylene or C<com:Sub>2-3< / com:Sub> alkenylene linker group either of which is optionally substituted with one or more groups R<com:Sup>3< / com:Sup> as defined above. Suitably Y is a C<com:Sub>1-3< / com:Sub> alkylene or C<com:Sub>2-3< / com:Sub> alkenylene linker group either of which is optionally substituted with one or more groups R<com:Sup>3< / com:Sup> as defined above. In one embodiment, for compounds of general formulae (Va), (V), (Vla), (Vl), (Xa) and (X) Y is bond, or a C<com:Sub>1-3< / com:Sub> alkylene linker group which is optionally substituted with one or more groups R<com:Sup>3< / com:Sup> as defined above. Suitably Y is a C<com:Sub>1-3< / com:Sub> alkylene linker group which is optionally substituted with one or more groups R<com:Sup>3< / com:Sup> as defined above. In one embodiment, for compounds of general formulae (Ia), (I), (IIa), (II), (IIIxa), (IIIx), (IIIya), (IIIy), (IIIxz), (IIIyz), (IVa) and (IV) Y is a bond, -CH<com:Sub>2< / com:Sub>-, -CH<com:Sub>2< / com:Sub>CH<com:Sub>2< / com:Sub>-, -CH=CH- or - CH=C(CH<com:Sub>3< / com:Sub>)-; suitably -CH<com:Sub>2< / com:Sub>-, -CH<com:Sub>2< / com:Sub>CH<com:Sub>2< / com:Sub>-, -CH=CH- or -CH=C(CH<com:Sub>3< / com:Sub>)-, in particular -CH<com:Sub>2< / com:Sub>CH<com:Sub>2< / com:Sub>- or -CH=CH-. In one embodiment, for compounds of general formulae (Va), (V), (Vla), (Vl), (Xa) and (X) Y is a bond, -CH<com:Sub>2< / com:Sub>- or -CH<com:Sub>2< / com:Sub>CH<com:Sub>2< / com:Sub>-; suitably -CH<com:Sub>2< / com:Sub>- or -CH<com:Sub>2< / com:Sub>CH<com:Sub>2< / com:Sub>-, in particular -CH<com:Sub>2< / com:Sub>CH<com:Sub>2< / com:Sub>. In one embodiment, for compounds of general formulae (Ia), (I), (IIa), (II), (IIIxa), (IIIx), (IIIya), (IIIy), (IIIxz), (IIIyz), (IVa) and (IV) Y is a bond, an unsubstituted C<com:Sub>1-3< / com:Sub> alkylene group, a C<com:Sub>1-3< / com:Sub> alkylene group substituted with OH, or a C<com:Sub>1-3< / com:Sub> alkenylene group. For example, Y may be a bond, -CH<com:Sub>2< / com:Sub>-, -CH<com:Sub>2< / com:Sub>CH<com:Sub>2< / com:Sub>-, -CH(OH)-CH<com:Sub>2< / com:Sub>-, -CH=CH- or -CH=C(CH<com:Sub>3< / com:Sub>)-, in particular a bond, -CH<com:Sub>2< / com:Sub>-, -CH<com:Sub>-2< / com:Sub>-CH<com:Sub>2< / com:Sub>-, -CH=CH- or -CH=C(CH<com:Sub>3< / com:Sub>)-, especially -CH<com:Sub>2< / com:Sub>-, -CH<com:Sub>2< / com:Sub>-CH<com:Sub>2< / com:Sub>-, - CH=CH- or -CH=C(CH<com:Math><semantics>3<annotation encoding="application / x-tex">_3< / annotation>< / semantics>< / com:Math>)-. In one embodiment, for compounds of general formulae (Va), (V), (Vla), (Vl), (Xa) and (X) Y is a bond, an unsubstituted C<com:Sub>1-3< / com:Sub> alkylene group or a C<com:Sub>1-3< / com:Sub> alkylene group substituted with OH. For example, Y may be a bond, -CH<com:Sub>2< / com:Sub>-, -CH<com:Sub>2< / com:Sub>CH<com:Sub>2< / com:Sub>-or -CH(OH)-CH<com:Sub>2< / com:Sub>-. In one embodiment, Y is an C<com:Sub>1-15< / com:Sub> alkylene linker, more suitably C<com:Sub>1-12< / com:Sub>, C<com:Sub>1-10< / com:Sub> or C<com:Sub>1-8< / com:Sub> alkylene linker and is substituted with an OH group. In this case, the OH group may be separated from the R<com:Sup>4< / com:Sup> moiety by a single CH<com:Sub>2< / com:Sub> group such that the linker Y is a group Y<com:Sup>4< / com:Sup>-CH(OH)-CH<com:Sub>2< / com:Sub>, where Y<com:Sup>4< / com:Sup> is as defined for Y, but is shorter by two carbon atoms. For example, Y may be -CH(OH)-CH<com:Sub>2< / com:Sub>-. This Y linker is particularly suitable when R4 is CN or R4 is CH(XR10)(XR11) e.g. CH(OR<com:Sup>10< / com:Sup>)(OR<com:Sup>11< / com:Sup>) wherein R<com:Sup>10< / com:Sup> and R<com:Sup>11< / com:Sup> are as defined above, but particularly wherein the XR<com:Sup>10< / com:Sup> and XR<com:Sup>11< / com:Sup> e.g. OR<com:Sup>10< / com:Sup> and OR<com:Sup>11< / com:Sup> groups together with the carbon atom to which they are attached form a cyclic group, e.g. a cyclic acetal group such as a 1,3-dioxane or 1,3- dioxolane ring. In one embodiment, R<com:Sup>3< / com:Sup> is H. In one embodiment, R<com:Sup>3< / com:Sup> is halo. In one embodiment, R<com:Sup>3< / com:Sup> is OH. In one embodiment, R<com:Sup>3< / com:Sup> is NR<com:Sup>8< / com:Sup>R<com:Sup>9< / com:Sup>, wherein each of R<com:Sup>8< / com:Sup> and R<com:Sup>9< / com:Sup> are suitably independently selected from H, methyl, ethyl, benzyl and tert-butyoxycarbonyl. In one embodiment, R<com:Sup>3< / com:Sup> is a protected OH group. In one embodiment, R<com:Sup>3< / com:Sup> is a protected OH group which is not stable in a basic environment such that treatment with a base converts the protected OH group to OH. Examples of such groups are well known in the art and include a group OC(O)R<com:Sup>14< / com:Sup>, wherein R<com:Sup>14< / com:Sup> is a group R<com:Sup>10< / com:Sup> as defined above for general formula (Ia) or (I), and is suitably C<com:Sub>1-6< / com:Sub> alkyl or benzyl, or C<com:Sub>1-6< / com:Sub> alkyl or phenyl. In another embodiment, R<com:Sup>3< / com:Sup> is a protected OH group which is stable in a basic environment. Examples of such groups include OSi(R<com:Sup>16< / com:Sup>)<com:Sub>3< / com:Sub>, where each R<com:Sup>16< / com:Sup> is independently a group R<com:Sup>13< / com:Sup> as defined above for general formula (Ia) or (I), and is suitably <com:Math><semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics>< / com:Math> alkyl or phenyl. In one embodiment, <com:Math><semantics>Si(R16)3<annotation encoding="application / x-tex">Si(R^{16})_3< / annotation>< / semantics>< / com:Math> is selected from the group consisting of trimethylsilyl (TMS), triethylsilyl (TES), triphenylsilyl (TPS), tri- isopropylsilyl (TIPS), thexyldimethylsilyl (TDS), tert-butyldiphenylsilyl (TBDPS), tert- butyldimethylsilyl (TBDMS or TBS), di-tert-butylmethylsilyl (DTBMS), diethylisopropylsilyl (DEIPS) and dimethylisopropylsilyl (DMIPS), in particular TMS, TES, TIPS, TBDMS and TBDPS. In one embodiment R<com:Sup>3< / com:Sup> is H, halo, OH, OC(O)R<com:Sup>14< / com:Sup>, OSi(R<com:Sup>16< / com:Sup>)<com:Sub>3< / com:Sub>, or NR<com:Sup>8< / com:Sup>R<com:Sup>9< / com:Sup>; wherein <com:Math><semantics>R14<annotation encoding="application / x-tex">R^{14}< / annotation>< / semantics>< / com:Math> is <com:Math><semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics>< / com:Math> alkyl or phenyl; each R<com:Sup>16< / com:Sup> is independently C<com:Sub>1-6< / com:Sub> alkyl or phenyl; and each R<com:Sup>8< / com:Sup> and R<com:Sup>9< / com:Sup> is independently H, methyl, ethyl or tert-butoxycarbonyl. In one embodiment, each R<com:Sup>3< / com:Sup> is independently halo, OR<com:Sup>8< / com:Sup> or NR<com:Sup>8< / com:Sup>R<com:Sup>9< / com:Sup>; wherein each of R<com:Sup>8< / com:Sup> and R<com:Sup>9< / com:Sup> is independently H or C<com:Sub>1-4< / com:Sub> alkyl. In one embodiment, each R<com:Sup>3< / com:Sup> is independently halo, OR<com:Sup>8< / com:Sup> or NR<com:Sup>8< / com:Sup>R<com:Sup>9< / com:Sup>; wherein each of R<com:Sup>8< / com:Sup> and R<com:Sup>9< / com:Sup> is independently selected from H, methyl or ethyl, especially H or methyl. In one embodiment, Y and <com:Math><semantics>R4<annotation encoding="application / x-tex">R^4< / annotation>< / semantics>< / com:Math> together form a =CH<com:Sub>2< / com:Sub> group. In one embodiment, when present in the R<com:Sub>4< / com:Sub> moiety, each R<com:Sup>10< / com:Sup> and R<com:Sup>11< / com:Sup> is independently: a. hydrogen; or b. <com:Math><semantics>C1−10<annotation encoding="application / x-tex">C_{1-10}< / annotation>< / semantics>< / com:Math> alkyl, <com:Math><semantics>C2−10<annotation encoding="application / x-tex">C_{2-10}< / annotation>< / semantics>< / com:Math> alkenyl or <com:Math><semantics>C2−10<annotation encoding="application / x-tex">C_{2-10}< / annotation>< / semantics>< / com:Math> alkynyl, any of which is optionally substituted with one or more substituents as described above; or C. a 6- to 10- membered aryl or 5- to 10-membered heteroaryl group either of which is optionally substituted with one or more substituents as described above; or d. a polyethylene glycol residue; or e. when R<com:Sup>4< / com:Sup> is CH(XR<com:Sup>10< / com:Sup>)(XR<com:Sup>11< / com:Sup>), CH(R<com:Sup>10< / com:Sup>)(XR<com:Sup>11< / com:Sup>), NR<com:Sup>10< / com:Sup>R<com:Sup>11< / com:Sup>, BR<com:Sup>10< / com:Sup>R<com:Sup>11< / com:Sup>, CH[C(O)OR<com:Sup>10< / com:Sup>]<com:Sub>2< / com:Sub> or CH(BR<com:Sup>10< / com:Sup>R<com:Sup>11< / com:Sup>)<com:Sub>2< / com:Sub>, an R<com:Sup>10< / com:Sup> and an R<com:Sup>11< / com:Sup> group, together with the atom or atoms to which they are attached, may combine to form a 3- to 10-membered heterocylic ring, more suitably a 5- to 6- membered heterocyclic ring. In one embodiment, each R<com:Sup>10< / com:Sup> and R<com:Sup>11< / com:Sup> is independently: a. hydrogen; or b. C<com:Sub>1-10< / com:Sub> alkyl, C<com:Sub>2-10< / com:Sub> alkenyl or C<com:Sub>2-10< / com:Sub> alkynyl, any of which is optionally substituted with one or more substituents as described above; or C. a 6- to 10- membered aryl or 5- to 10-membered heteroaryl group either of which is optionally substituted with one or more substituents as described above; or d. a polyethylene glycol residue; or e. when R<com:Sup>4< / com:Sup> is CH(OR<com:Sup>10< / com:Sup>)(OR<com:Sup>11< / com:Sup>), CH(R<com:Sup>10< / com:Sup>)(OR<com:Sup>11< / com:Sup>), CH(SR<com:Sup>10< / com:Sup>)(SR<com:Sup>11< / com:Sup>), NR<com:Sup>10< / com:Sup>R<com:Sup>11< / com:Sup>, BR<com:Sup>10< / com:Sup>R<com:Sup>11< / com:Sup>, CH[C(O)OR<com:Sup>10< / com:Sup>]<com:Sub>2< / com:Sub> or CH(BR<com:Sup>10< / com:Sup>R<com:Sup>11< / com:Sup>)<com:Sub>2< / com:Sub>, an R<com:Sup>10< / com:Sup> and an R<com:Sup>11< / com:Sup> group, together with the atom or atoms to which they are attached, may combine to form a 3- to 10-membered heterocylic ring. Suitably, each R<com:Sup>10< / com:Sup> and R<com:Sup>11< / com:Sup> is independently a. hydrogen; or b. <com:Math><semantics>C1−10<annotation encoding="application / x-tex">C_{1-10}< / annotation>< / semantics>< / com:Math> alkyl, <com:Math><semantics>C2−10<annotation encoding="application / x-tex">C_{2-10}< / annotation>< / semantics>< / com:Math> alkenyl or <com:Math><semantics>C2−10<annotation encoding="application / x-tex">C_{2-10}< / annotation>< / semantics>< / com:Math> alkynyl optionally substituted with one or more substituents as described above; or C. a 6- to 10-membered aryl group or a 5- to 6-membered heteroaryl group optionally substituted with one or more substituents as described above; or e. when R<com:Sup>4< / com:Sup> is C(O)NR<com:Sup>10< / com:Sup>R<com:Sup>11< / com:Sup> or NR<com:Sup>10< / com:Sup>R<com:Sup>11< / com:Sup>, an R<com:Sup>10< / com:Sup> and an R<com:Sup>11< / com:Sup> group, together with the nitrogen to which they are attached, combine to form a pyrrolidine or piperidine ring or when R<com:Sup>4< / com:Sup> is CH(XR<com:Sup>10< / com:Sup>)(XR<com:Sup>11< / com:Sup>), for example CH(OR<com:Sup>10< / com:Sup>)(OR<com:Sup>11< / com:Sup>), the XR<com:Sup>10< / com:Sup> and XR<com:Sup>11< / com:Sup> group, together with the carbon atom to which they are attached, combine to form a ring; suitably X is O and the ring is a 1,3-dioxane or 1,3-dioxolane ring; or when R<com:Sup>4< / com:Sup> is BR<com:Sup>10< / com:Sup>R<com:Sup>11< / com:Sup>, the R<com:Sup>10< / com:Sup> and R<com:Sup>11< / com:Sup> groups, together with the boron atom to which they are attached combine to form a bridged boron-containing ring such as 9-BBN. Suitably, each R<com:Sup>10< / com:Sup> and R<com:Sup>11< / com:Sup> is independently: a. hydrogen; or b. <com:Math><semantics>C1−10<annotation encoding="application / x-tex">C_{1-10}< / annotation>< / semantics>< / com:Math> alkyl, <com:Math><semantics>C2−10<annotation encoding="application / x-tex">C_{2-10}< / annotation>< / semantics>< / com:Math> alkenyl or <com:Math><semantics>C2−10<annotation encoding="application / x-tex">C_{2-10}< / annotation>< / semantics>< / com:Math> alkynyl optionally substituted with one or more substituents as described above; or C. a 6- to 10-membered aryl group optionally substituted with one or more substituents as described above; or e. when R<com:Sup>4< / com:Sup> is C(O)NR<com:Sup>10< / com:Sup>R<com:Sup>11< / com:Sup> or NR<com:Sup>10< / com:Sup>R<com:Sup>11< / com:Sup>, an R<com:Sup>10< / com:Sup> and an R<com:Sup>11< / com:Sup> group, together with the nitrogen to which they are attached, combine to form a pyrrolidine or piperidine ring or when R<com:Sup>4< / com:Sup> is CH(OR<com:Sup>10< / com:Sup>)(OR<com:Sup>11< / com:Sup>), the OR<com:Sup>10< / com:Sup> and OR<com:Sup>11< / com:Sup> group, together with the carbon atom to which they are attached, combine to form a 1,3-dioxane or 1,3-dioxolane ring; or when R4 is BR<com:Sup>10< / com:Sup>R<com:Sup>11< / com:Sup>, the R<com:Sup>10< / com:Sup> and R<com:Sup>11< / com:Sup> groups, together with the boron atom to which they are attached combine to form a bridged boron-containing ring such as 9-BBN. In one embodiment, when R<com:Sup>4< / com:Sup> is NR<com:Sup>10< / com:Sup>R<com:Sup>11< / com:Sup>, R<com:Sup>10< / com:Sup> is H or C<com:Sub>1-4< / com:Sub> alkyl and R<com:Sup>11< / com:Sup> is a 5-10 membered heteroaryl group such as tetrazole. Other examples of R<com:Sup>4< / com:Sup> groups include azide and tetrazole. When <com:Math><semantics>R4<annotation encoding="application / x-tex">R^4< / annotation>< / semantics>< / com:Math> is <com:Math><semantics>OSi(R13)3<annotation encoding="application / x-tex">OSi(R^{13})_3< / annotation>< / semantics>< / com:Math>, suitably each <com:Math><semantics>R13<annotation encoding="application / x-tex">R^{13}< / annotation>< / semantics>< / com:Math> is independently selected from: a. <com:Math><semantics>C1−10<annotation encoding="application / x-tex">C_{1-10}< / annotation>< / semantics>< / com:Math> alkyl, <com:Math><semantics>C2−10<annotation encoding="application / x-tex">C_{2-10}< / annotation>< / semantics>< / com:Math> alkenyl or <com:Math><semantics>C2−10<annotation encoding="application / x-tex">C_{2-10}< / annotation>< / semantics>< / com:Math> alkynyl optionally substituted with one or more substituents as described above; or b. a 6- to 10- membered aryl or 5- to 10-membered heteroaryl group optionally substituted with one or more substituents as described above. More suitably, each R<com:Sup>13< / com:Sup> is independently selected from: a. C<com:Sub>1-10< / com:Sub> alkyl, C<com:Sub>2-10< / com:Sub> alkenyl or C<com:Sub>2-10< / com:Sub> alkynyl optionally substituted with one or more substituents as described above; or b. a 6- to 10- membered aryl group optionally substituted with one or more substituents as described above. Still more suitably, each R<com:Sup>13< / com:Sup> is independently selected from C<com:Sub>1-10< / com:Sub> alkyl or phenyl, either of which is optionally substituted as described above. In one embodiment, each R<com:Sup>13< / com:Sup> is independently selected from C<com:Sub>1-6< / com:Sub> alkyl (in particular methyl, ethyl, isopropyl, tert-butyl, hexyl) and phenyl. In one embodiment, <com:Math><semantics>Si(R13)3<annotation encoding="application / x-tex">Si(R^{13})_3< / annotation>< / semantics>< / com:Math> is selected from the group consisting of trimethylsilyl (TMS), triethylsilyl (TES), triphenylsilyl (TPS), tri-isopropylsilyl (TIPS), thexyldimethylsilyl (TDS), tert-butyldiphenylsilyl (TBDPS), tert-butyldimethylsilyl (TBDMS or TBS), di-tert- butylmethylsilyl (DTBMS), diethylisopropylsilyl (DEIPS) and dimethylisopropylsilyl (DMIPS), in particular TMS, TES, TIPS, TBDMS and TBDPS. Suitable substituents for alkyl, alkenyl and alkynyl R<com:Sup>10< / com:Sup> and R<com:Sup>11< / com:Sup> groups include halo, NO<com:Sub>2< / com:Sub>, CN, OR<com:Sup>19< / com:Sup>, SR<com:Sup>19< / com:Sup>, C(O)OR<com:Sup>19< / com:Sup>, SO<com:Sub>2< / com:Sub>R<com:Sup>19< / com:Sup>, SO<com:Sub>3< / com:Sub>R<com:Sup>19< / com:Sup>, OSO<com:Sub>3< / com:Sub>R<com:Sup>19< / com:Sup>, N(R<com:Sup>19< / com:Sup>)<com:Sub>2< / com:Sub>, and a 6- to 10- membered aryl or 5- to 14-membered heteroaryl group, either of which is optionally substituted with <com:Math><semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics>< / com:Math> alkyl, <com:Math><semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics>< / com:Math> haloalkyl, halo, NO<com:Sub>2< / com:Sub>, CN, OR<com:Sup>19< / com:Sup>, SO<com:Sub>2< / com:Sub>R<com:Sup>19< / com:Sup>, SO<com:Sub>3< / com:Sub>R<com:Sup>19< / com:Sup> or N(R<com:Sup>19< / com:Sup>)<com:Sub>2< / com:Sub>; where R<com:Sup>19< / com:Sup> is as defined above. Similarly, suitable substituents for alkyl, alkenyl and alkynyl R<com:Sup>13< / com:Sup> groups include halo, NO<com:Sub>2< / com:Sub>, CN, OR<com:Sup>19< / com:Sup>, SR<com:Sup>19< / com:Sup>, C(O)OR<com:Sup>19< / com:Sup>, SO<com:Sub>2< / com:Sub>R<com:Sup>19< / com:Sup>, SO<com:Sub>3< / com:Sub>R<com:Sup>19< / com:Sup>, OSO<com:Sub>3< / com:Sub>R<com:Sup>19< / com:Sup>, N(R<com:Sup>19< / com:Sup>)<com:Sub>2< / com:Sub>, and a 6- to 10- membered aryl or 5- to 14-membered heteroaryl group, either of which is optionally substituted with <com:Math><semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics>< / com:Math> alkyl, <com:Math><semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics>< / com:Math> haloalkyl, halo, <com:Math><semantics>NO2<annotation encoding="application / x-tex">NO_2< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>CN<annotation encoding="application / x-tex">CN< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>OR19<annotation encoding="application / x-tex">OR^{19}< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>SO2R19<annotation encoding="application / x-tex">SO_2R^{19}< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>SO3R19<annotation encoding="application / x-tex">SO_3R^{19}< / annotation>< / semantics>< / com:Math> or <com:Math><semantics>N(R19)2<annotation encoding="application / x-tex">N(R^{19})_2< / annotation>< / semantics>< / com:Math>; where <com:Math><semantics>R19<annotation encoding="application / x-tex">R^{19}< / annotation>< / semantics>< / com:Math> is as defined above. More suitable substituents for these R<com:Sup>10< / com:Sup> and R<com:Sup>11< / com:Sup> groups include halo, OR<com:Sup>19< / com:Sup>, C(O)OR<com:Sup>19< / com:Sup>, N(R<com:Sup>19< / com:Sup>)<com:Sub>2< / com:Sub>, SO<com:Sub>3< / com:Sub>R<com:Sup>19< / com:Sup>, OSO<com:Sub>3< / com:Sub>R<com:Sup>19< / com:Sup> or a 6- to 10-membered aryl group optionally substituted as described above, and more suitable substituents for these R<com:Sup>13< / com:Sup> groups include halo, OR<com:Sup>19< / com:Sup>, <com:Math><semantics>C(O)OR19<annotation encoding="application / x-tex">C(O)OR^{19}< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>N(R19)2<annotation encoding="application / x-tex">N(R^{19})_2< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>SO3R19<annotation encoding="application / x-tex">SO_3R^{19}< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>OSO3R19<annotation encoding="application / x-tex">OSO_3R^{19}< / annotation>< / semantics>< / com:Math> or a 6- to 10-membered aryl group optionally substituted as described above. More suitable substituents for these R<com:Sup>10< / com:Sup>, R<com:Sup>11< / com:Sup> and R<com:Sup>13< / com:Sup> groups include halo, C<com:Sub>1-4< / com:Sub> alkyl, C<com:Sub>1-4< / com:Sub> haloalkyl, -O-C<com:Sub>1-4< / com:Sub> alkyl, -O-C<com:Sub>1-4< / com:Sub> haloalkyl, C(O)OH, SO<com:Sub>2< / com:Sub>OH, -NH(C<com:Sub>1-4< / com:Sub> alkyl) or -N(C<com:Sub>1-4< / com:Sub> alkyl)<com:Sub>2< / com:Sub>; for example fluoro, chloro, methyl, ethyl, trifluoromethyl, methoxy, ethoxy, trifluoromethoxy, C(O)OH, SO<com:Sub>2< / com:Sub>OH, amino, methyl amino and dimethylamino. More suitable substituents for these R<com:Sup>10< / com:Sup>, R<com:Sup>11< / com:Sup> and R<com:Sup>13< / com:Sup> groups include halo, C<com:Sub>1-4< / com:Sub> alkyl, C<com:Sub>1-4< / com:Sub> haloalkyl, -O-C<com:Sub>1-4< / com:Sub> alkyl, -O-C<com:Sub>1-4< / com:Sub> haloalkyl, C(O)OH, SO<com:Sub>2< / com:Sub>OH, -NH<com:Sub>2< / com:Sub>, -NH(C<com:Sub>1-4< / com:Sub> alkyl) or -N(C<com:Sub>1-1< / com:Sub> 4 alkyl)<com:Sub>2< / com:Sub>; for example fluoro, chloro, methyl, ethyl, trifluoromethyl, methoxy, ethoxy, trifluoromethoxy, C(O)OH, SO<com:Sub>2< / com:Sub>OH, amino, methyl amino and dimethylamino. Suitable substituents for aryl and heteroaryl R<com:Sup>10< / com:Sup> and R<com:Sup>11< / com:Sup> groups include C<com:Sub>1-6< / com:Sub> alkyl, C<com:Sub>1-6< / com:Sub> haloalkyl, halo, NO<com:Sub>2< / com:Sub>, CN, <com:Math><semantics>OR19<annotation encoding="application / x-tex">OR^{19}< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>SR19<annotation encoding="application / x-tex">SR^{19}< / annotation>< / semantics>< / com:Math> or <com:Math><semantics>N(R19)2<annotation encoding="application / x-tex">N(R^{19})_2< / annotation>< / semantics>< / com:Math>. Similarly, suitable subsitutents for aryl and heteroaryl R<com:Sup>13< / com:Sup> groups include C<com:Sub>1-6< / com:Sub> alkyl, C<com:Sub>1-6< / com:Sub> haloalkyl, halo, NO<com:Sub>2< / com:Sub>, CN, OR<com:Sup>19< / com:Sup>, SR<com:Sup>19< / com:Sup> or N(R<com:Sup>19< / com:Sup>)<com:Sub>2< / com:Sub>. More suitable substituents for aryl and heteoraryl R<com:Sup>10< / com:Sup> and R<com:Sup>11< / com:Sup> groups include C<com:Sub>1-4< / com:Sub> alkyl, C<com:Sub>1-4< / com:Sub> haloalkyl, halo, OR<com:Sup>19< / com:Sup> or N(R<com:Sup>19< / com:Sup>)<com:Sub>2< / com:Sub>; and similarly, more suitable substituents for aryl and heteroaryl R<com:Sup>13< / com:Sup> groups include C<com:Sub>1-4< / com:Sub> alkyl, C<com:Sub>1-4< / com:Sub> haloalkyl, halo, OR<com:Sup>19< / com:Sup> or N(R<com:Sup>19< / com:Sup>)<com:Sub>2< / com:Sub>. Particularly suitable substituents for aryl and heteroaryl R<com:Sup>10< / com:Sup>, R<com:Sup>11< / com:Sup> and R<com:Sup>13< / com:Sup> groups include halo, C<com:Sub>1-4< / com:Sub> alkyl, C<com:Sub>1-4< / com:Sub> haloalkyl, -O-C<com:Sub>1-4< / com:Sub> alkyl, -O-C<com:Sub>1-4< / com:Sub> haloalkyl, -NH(C<com:Sub>1-4< / com:Sub> alkyl) or -N(C<com:Sub>1-4< / com:Sub> alkyl)2. Specific examples of substituents for aryl and heteroaryl R<com:Sup>10< / com:Sup>, R<com:Sup>11< / com:Sup> and R<com:Sup>13< / com:Sup> groups include fluoro, chloro, methyl, ethyl, trifluoromethyl, methoxy, ethoxy, trifluoromethoxy, amino, methyl amino and dimethylamino. As set out above, with respect to groups R<com:Sup>10< / com:Sup> and R<com:Sup>11< / com:Sup>, each R<com:Sup>19< / com:Sup> is independently selected H, C<com:Sub>1-6< / com:Sub> alkyl, C<com:Sub>1-6< / com:Sub> haloalkyl, or a 6- to 14- membered aryl or 5- to 14-membered heteroaryl group either of which is optionally substituted with one or more substituents selected from halo, C<com:Sub>1-6< / com:Sub> alkyl and C<com:Sub>1-6< / com:Sub> haloalkyl. Suitably, R<com:Sup>19< / com:Sup> is H, C<com:Sub>1-6< / com:Sub> alkyl, C<com:Sub>1-6< / com:Sub> haloalkyl, or a 6- to 10- membered aryl or 5 to 10- membered heteroaryl group optionally substituted with one or more substituents selected from halo, C<com:Sub>1-4< / com:Sub> alkyl and C<com:Sub>1-4< / com:Sub> haloalkyl. More suitably, <com:Math><semantics>R19<annotation encoding="application / x-tex">R^{19}< / annotation>< / semantics>< / com:Math> is hydrogen, <com:Math><semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics>< / com:Math> alkyl, <com:Math><semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics>< / com:Math> haloalkyl or phenyl optionally substituted with one or more halo, C<com:Sub>1-4< / com:Sub> alkyl or C<com:Sub>1-4< / com:Sub> haloalkyl substituents. Specific examples of R<com:Sup>19< / com:Sup> include H, methyl, ethyl, trifluoromethyl or phenyl optionally substituted with one or more substituents selected from fluoro, chloro, methyl, ethyl and trifluoromethyl. As set out above, with respect to group R<com:Sup>13< / com:Sup>, each R<com:Sup>19< / com:Sup> is independently H, C<com:Sub>1-6< / com:Sub> alkyl or C<com:Sub>1-6< / com:Sub> haloalkyl. In one embodiment, R<com:Sup>19< / com:Sup> is H or C<com:Sub>1-6< / com:Sub> alkyl such as C<com:Sub>1-4< / com:Sub> alkyl, for example, methyl or ethyl. Specific examples of R<com:Sup>19< / com:Sup> include H, methyl, ethyl or trifluoromethyl. In some particularly suitable compounds of general formula (la)), R<com:Sup>4< / com:Sup> is C(O)OR<com:Sup>10< / com:Sup>, OR<com:Sup>10< / com:Sup>, SO<com:Sub>3< / com:Sub>R<com:Sup>10< / com:Sup>, OSO<com:Sub>3< / com:Sub>R<com:Sup>10< / com:Sup>, halo, CN, azide, OSi(R<com:Sup>13< / com:Sup>)<com:Sub>3< / com:Sub>, C(O)R<com:Sup>10< / com:Sup>, NR<com:Sup>10< / com:Sup>C(O)NR<com:Sup>10< / com:Sup>SO<com:Sub>2< / com:Sub>R<com:Sup>11< / com:Sup>, <com:Math><semantics>NR10C(O)NR10SO2N<annotation encoding="application / x-tex">NR^{10}C(O)NR^{10}SO_2N< / annotation>< / semantics>< / com:Math> <com:Math><semantics>R10R11<annotation encoding="application / x-tex">R^{10}R^{11}< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>NR10SO2R11<annotation encoding="application / x-tex">NR^{10}SO_2R^{11}< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>CH(XR10)(XR11)<annotation encoding="application / x-tex">CH(XR^{10})(XR^{11})< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>CH[C(O)OR10]2<annotation encoding="application / x-tex">CH[C(O)OR^{10}]_2< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>BR10R11<annotation encoding="application / x-tex">BR^{10}R^{11}< / annotation>< / semantics>< / com:Math> or phthalimide. In some particularly suitable compounds of general formula (la), (lla), (llxa), (llxa), (llxz), (IIIyz), (IVa), (Va), (VIa) and (Xa) <com:Math><semantics>R4<annotation encoding="application / x-tex">R^4< / annotation>< / semantics>< / com:Math> is <com:Math><semantics>C(O)OR10<annotation encoding="application / x-tex">C(O)OR^{10}< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>OR10<annotation encoding="application / x-tex">OR^{10}< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>SO3R10<annotation encoding="application / x-tex">SO_3R^{10}< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>OSO3R10<annotation encoding="application / x-tex">OSO_3R^{10}< / annotation>< / semantics>< / com:Math>, halo, <com:Math><semantics>CN<annotation encoding="application / x-tex">CN< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>C(O)R10<annotation encoding="application / x-tex">C(O)R^{10}< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>CH(XR10)(XR11)<annotation encoding="application / x-tex">CH(XR^{10})(XR^{11})< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>CH[C(O)OR10]2<annotation encoding="application / x-tex">CH[C(O)OR^{10}]_2< / annotation>< / semantics>< / com:Math> or <com:Math><semantics>BR10R11<annotation encoding="application / x-tex">BR^{10}R^{11}< / annotation>< / semantics>< / com:Math>; and each <com:Math><semantics>R10<annotation encoding="application / x-tex">R^{10}< / annotation>< / semantics>< / com:Math> and <com:Math><semantics>R11<annotation encoding="application / x-tex">R^{11}< / annotation>< / semantics>< / com:Math> is independently H, C<com:Sub>1-6< / com:Sub> alkyl or benzyl; or, when R<com:Sup>4< / com:Sup> is CH(XR<com:Sup>10< / com:Sup>)(XR<com:Sup>11< / com:Sup>) or BR<com:Sup>10< / com:Sup>R<com:Sup>11< / com:Sup>, R<com:Sup>10< / com:Sup> and R<com:Sup>11< / com:Sup> together with the atom or atoms to which they are attached, may combine to form a 3- to 10-membered heterocyclic ring; or R<com:Sup>4< / com:Sup> is C(O)NR<com:Sup>10< / com:Sup>R<com:Sup>11< / com:Sup> wherein each R<com:Sup>10< / com:Sup> and R<com:Sup>11< / com:Sup> is independently substituted with C(O)OR<com:Sup>19< / com:Sup>, <com:Math><semantics>OR19<annotation encoding="application / x-tex">OR^{19}< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>SO3R19<annotation encoding="application / x-tex">SO_3R^{19}< / annotation>< / semantics>< / com:Math>, or <com:Math><semantics>OSO3R19<annotation encoding="application / x-tex">OSO_3R^{19}< / annotation>< / semantics>< / com:Math> and <com:Math><semantics>R19<annotation encoding="application / x-tex">R^{19}< / annotation>< / semantics>< / com:Math> is H. In some particularly suitable compounds of general formula (I), (II), (IIIx), (IIIy), (IV), (V), (VI) and (X) R<com:Sup>4< / com:Sup> is C(O)OR<com:Sup>10< / com:Sup>, OR<com:Sup>10< / com:Sup>, SO<com:Sub>3< / com:Sub>R<com:Sup>10< / com:Sup>, OSO<com:Sub>3< / com:Sub>R<com:Sup>10< / com:Sup>, halo, CN, C(O)R<com:Sup>10< / com:Sup>, CH(OR<com:Sup>10< / com:Sup>)(OR<com:Sup>11< / com:Sup>), CH[C(O)OR<com:Sup>10< / com:Sup>]<com:Sub>2< / com:Sub> or BR<com:Sup>10< / com:Sup>R<com:Sup>11< / com:Sup>;and each R<com:Sup>10< / com:Sup> and R<com:Sup>11< / com:Sup> is independently H, C<com:Sub>1-6< / com:Sub> alkyl or benzyl; or, when R<com:Sup>4< / com:Sup> is CH(OR<com:Sup>10< / com:Sup>)(OR<com:Sup>11< / com:Sup>) or BR<com:Sup>10< / com:Sup>R<com:Sup>11< / com:Sup>, R<com:Sup>10< / com:Sup> and R<com:Sup>11< / com:Sup> together with the atom or atoms to which they are attached, may combine to form a 3- to 10-membered heterocyclic ring; or R<com:Sup>4< / com:Sup> is C(O)NR<com:Sup>10< / com:Sup>R<com:Sup>11< / com:Sup> wherein each R<com:Sup>10< / com:Sup> and R<com:Sup>11< / com:Sup> is independently substituted with C(O)OR<com:Sup>19< / com:Sup>, <com:Math><semantics>OR19<annotation encoding="application / x-tex">OR^{19}< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>SO3R19<annotation encoding="application / x-tex">SO_3R^{19}< / annotation>< / semantics>< / com:Math>, or <com:Math><semantics>OSO3R19<annotation encoding="application / x-tex">OSO_3R^{19}< / annotation>< / semantics>< / com:Math> and <com:Math><semantics>R19<annotation encoding="application / x-tex">R^{19}< / annotation>< / semantics>< / com:Math> is H. When R<com:Sup>4< / com:Sup> is CH(XR<com:Sup>10< / com:Sup>)(XR<com:Sup>11< / com:Sup>) and R<com:Sup>10< / com:Sup> and R<com:Sup>11< / com:Sup> together with the atom or atoms to which they are attached combine to form a 3- to 10-membered heterocyclic ring, suitably R4 is a 3-5 membered heterocyclic ring, in particular a 5-membered heterocyclic ring e.g. R<com:Sup>4< / com:Sup> is selected from: [Image disponible dans le document PDF, Image available in the PDF document] When R<com:Sup>4< / com:Sup> is CH(R<com:Sup>10< / com:Sup>)(XR<com:Sup>11< / com:Sup>) and R<com:Sup>10< / com:Sup> and R<com:Sup>11< / com:Sup> together with the atom or atoms to which they are attached combine to form a 3- to 10-membered heterocyclic ring, suitably R3 is a 3- membered heterocyclic ring e.g. R<com:Sup>4< / com:Sup> is selected from: and in particular is [Image disponible dans le document PDF, Image available in the PDF document] [Image disponible dans le document PDF, Image available in the PDF document] . Alternatively, the compound may be in the form of a salt such that: <com:Math><semantics>R4<annotation encoding="application / x-tex">R^4< / annotation>< / semantics>< / com:Math> is <com:Math><semantics>C(O)O−<annotation encoding="application / x-tex">C(O)O^-< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>O−<annotation encoding="application / x-tex">O^-< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>SO3−<annotation encoding="application / x-tex">SO_3^-< / annotation>< / semantics>< / com:Math>, or <com:Math><semantics>OSO3−<annotation encoding="application / x-tex">OSO_3^-< / annotation>< / semantics>< / com:Math>; or R<com:Sup>4< / com:Sup> is C(O)NR<com:Sup>10< / com:Sup>R<com:Sup>11< / com:Sup> wherein R<com:Sup>10< / com:Sup> and R<com:Sup>11< / com:Sup> are independently substituted with C(O)O<com:Sup>-< / com:Sup>, O<com:Sup>-< / com:Sup>, <com:Math><semantics>SO3−<annotation encoding="application / x-tex">SO_3^-< / annotation>< / semantics>< / com:Math>, or <com:Math><semantics>OSO3−<annotation encoding="application / x-tex">OSO_3^-< / annotation>< / semantics>< / com:Math>; and a counter ion is present as described above for basic addition salts. In one embodiment, <com:Math><semantics>R4<annotation encoding="application / x-tex">R^4< / annotation>< / semantics>< / com:Math> is <com:Math><semantics>C(O)OR10<annotation encoding="application / x-tex">C(O)OR^{10}< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>OR10<annotation encoding="application / x-tex">OR^{10}< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>C(O)NR10R11<annotation encoding="application / x-tex">C(O)NR^{10}R^{11}< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>SO3R10<annotation encoding="application / x-tex">SO_3R^{10}< / annotation>< / semantics>< / com:Math>, or <com:Math><semantics>OSO3R10<annotation encoding="application / x-tex">OSO_3R^{10}< / annotation>< / semantics>< / com:Math>. In one embodiment, <com:Math><semantics>R4<annotation encoding="application / x-tex">R^4< / annotation>< / semantics>< / com:Math> is <com:Math><semantics>OSi(R13)3<annotation encoding="application / x-tex">OSi(R^{13})_3< / annotation>< / semantics>< / com:Math>. In one embodiment, R<com:Sup>4< / com:Sup> is halo, CN, C(O)R<com:Sup>10< / com:Sup>, CH(XR<com:Sup>10< / com:Sup>)(XR<com:Sup>11< / com:Sup>), NR<com:Sup>10< / com:Sup>R<com:Sup>11< / com:Sup>, BR¹0R¹1, -CH=CH<com:Sub>2< / com:Sub>, -C≡CH, CH[C(O)OR¹0]<com:Sub>2< / com:Sub> or CH(BR¹0R¹1)<com:Sub>2< / com:Sub> or Y and R⁴ together form a =CH<com:Sub>2< / com:Sub> group. In one embodiment, R<com:Sup>4< / com:Sup> is halo, CN, C(O)R<com:Sup>10< / com:Sup>, CH(OR<com:Sup>10< / com:Sup>)(OR<com:Sup>11< / com:Sup>), NR<com:Sup>10< / com:Sup>R<com:Sup>11< / com:Sup>, BR¹0R¹1, -CH=CH₂, -C≡CH, CH[C(O)OR¹0]₂ or CH(BR¹0R¹1)₂ or Y and R⁴ together form a =CH<com:Sub>2< / com:Sub> group. In one embodiment, R<com:Sup>4< / com:Sup> is halo, CN, C(O)R<com:Sup>10< / com:Sup>, NR<com:Sup>10< / com:Sup>R<com:Sup>11< / com:Sup>, BR<com:Sup>10< / com:Sup>R<com:Sup>11< / com:Sup>, C(O)CH<com:Sub>2< / com:Sub>N<com:Sub>2< / com:Sub>, -CH=CH<com:Sub>2< / com:Sub>, - C≡CH, <com:Math><semantics>CH[C(O)OR10]2<annotation encoding="application / x-tex">CH[C(O)OR^{10}]_2< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>CH(BR10R11)2<annotation encoding="application / x-tex">CH(BR^{10}R^{11})_2< / annotation>< / semantics>< / com:Math>, azide, <com:Math><semantics>NO2<annotation encoding="application / x-tex">NO_2< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>NR10C(O)NR10SO2R11<annotation encoding="application / x-tex">NR^{10}C(O)NR^{10}SO_2R^{11}< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>C(O)NR10SO2R11<annotation encoding="application / x-tex">C(O)NR^{10}SO_2R^{11}< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>CH(XR10)(XR11)<annotation encoding="application / x-tex">CH(XR^{10})(XR^{11})< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>CH(R10)(XR11)<annotation encoding="application / x-tex">CH(R^{10})(XR^{11})< / annotation>< / semantics>< / com:Math> wherein each X is independently O, S or NR<com:Sup>8< / com:Sup>. When R<com:Sup>4< / com:Sup> is CH(XR<com:Sup>10< / com:Sup>)(XR<com:Sup>11< / com:Sup>), X is suitably O or S, e.g. O. In such compounds, when R<com:Sup>10< / com:Sup> and R<com:Sup>11< / com:Sup> combine to form a ring, it is suitably a 5- or 6-membered ring. More suitably, both X moieties are O and R<com:Sup>10< / com:Sup> and R<com:Sup>11< / com:Sup> form a 1,3-dioxane or 1,3-dioxolane ring. When <com:Math><semantics>R4<annotation encoding="application / x-tex">R^4< / annotation>< / semantics>< / com:Math> is <com:Math><semantics>CH(R10)(XR11)<annotation encoding="application / x-tex">CH(R^{10})(XR^{11})< / annotation>< / semantics>< / com:Math>, X is suitably O or S, e.g. O. In one embodiment, R<com:Sup>4< / com:Sup> is a carboxylic acid mimetic group. In one embodiment, R4 is a carboxylic acid mimetic group selected from tetrazole, substituted tetrazole, -SO<com:Sub>2< / com:Sub>-NHR<com:Sup>10< / com:Sup>, C(O)NH-SO<com:Sub>2< / com:Sub>R<com:Sup>10< / com:Sup> and NHC(O)NH-SO<com:Sub>2< / com:Sub>R<com:Sup>10< / com:Sup>; wherein R<com:Sup>10< / com:Sup> is as above defined for a compound of general formulae (la) or (l) and is suitably H, C<com:Sub>1-6< / com:Sub> alkyl, C<com:Sub>3-7< / com:Sub> cycloalkyl or 6- to 14- membered aryl (e.g. phenyl). Suitably, substituted tetrazole is tetrazole substituted with <com:Math><semantics>C1−4<annotation encoding="application / x-tex">C_{1-4}< / annotation>< / semantics>< / com:Math> alkyl, halo, OH, O(<com:Math><semantics>C1−4<annotation encoding="application / x-tex">C_{1-4}< / annotation>< / semantics>< / com:Math> alkyl) or SO<com:Sub>2< / com:Sub>R<com:Sup>10< / com:Sup> (e.g. SO<com:Sub>2< / com:Sub>(C<com:Sub>1-4< / com:Sub> alkyl), SO<com:Sub>2< / com:Sub>-phenyl or SO<com:Sub>2< / com:Sub>-tolyl). When R<com:Sup>4< / com:Sup> is a carboxylic acid mimetic group, it is suitably a tetrazolyl group, for example tetrazol-1-yl or tetrazol-5-yl. In one embodiment, <com:Math><semantics>R4<annotation encoding="application / x-tex">R^4< / annotation>< / semantics>< / com:Math> is halo, <com:Math><semantics>CN<annotation encoding="application / x-tex">CN< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>C(O)R10<annotation encoding="application / x-tex">C(O)R^{10}< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>CH(XR10)(XR11)<annotation encoding="application / x-tex">CH(XR^{10})(XR^{11})< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>CH=CH2<annotation encoding="application / x-tex">CH=CH_2< / annotation>< / semantics>< / com:Math>, -C≡CH, CH[C(O)OR<com:Sup>10< / com:Sup>]<com:Sub>2< / com:Sub>, BR<com:Sup>10< / com:Sup>R<com:Sup>11< / com:Sup> or Y and R<com:Sup>4< / com:Sup> together form a =CH<com:Sub>2< / com:Sub> group. In one embodiment, R<com:Sup>4< / com:Sup> is halo, CN, C(O)R<com:Sup>10< / com:Sup>, CH(OR<com:Sup>10< / com:Sup>)(OR<com:Sup>11< / com:Sup>), CH=CH<com:Sub>2< / com:Sub>, -C≡CH, CH[C(O)OR<com:Sup>10< / com:Sup>]<com:Sub>2< / com:Sub>, BR<com:Sup>10< / com:Sup>R<com:Sup>11< / com:Sup> or Y and R<com:Sup>4< / com:Sup> together form a =CH<com:Sub>2< / com:Sub> group. Suitably, <com:Math><semantics>R4<annotation encoding="application / x-tex">R^4< / annotation>< / semantics>< / com:Math> is <com:Math><semantics>C(O)OR10<annotation encoding="application / x-tex">C(O)OR^{10}< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>C(O)NR10R11<annotation encoding="application / x-tex">C(O)NR^{10}R^{11}< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>SO3R10<annotation encoding="application / x-tex">SO_3R^{10}< / annotation>< / semantics>< / com:Math>, or <com:Math><semantics>OSO3R10<annotation encoding="application / x-tex">OSO_3R^{10}< / annotation>< / semantics>< / com:Math>. More suitably, R<com:Sup>4< / com:Sup> is C(O)OR<com:Sup>10< / com:Sup>, SO<com:Sub>3< / com:Sub>R<com:Sup>10< / com:Sup>, or OSO<com:Sub>3< / com:Sub>R<com:Sup>10< / com:Sup> and R<com:Sup>10< / com:Sup> is H; or R<com:Sup>4< / com:Sup> is C(O)NR<com:Sup>10< / com:Sup>R<com:Sup>11< / com:Sup> substituted with C(O)OR<com:Sup>19< / com:Sup>, SO<com:Sub>3< / com:Sub>R<com:Sup>19< / com:Sup>, or OSO<com:Sub>3< / com:Sub>R<com:Sup>19< / com:Sup> and R<com:Sup>19< / com:Sup> is H. In other particularly suitable compounds R<com:Sup>4< / com:Sup> is halo, CN, C(O)R<com:Sup>10< / com:Sup>, CH(OR<com:Sup>10< / com:Sup>)(OR<com:Sup>11< / com:Sup>), <com:Math><semantics>NR10R11<annotation encoding="application / x-tex">NR^{10}R^{11}< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>CH[C(O)OR10]2<annotation encoding="application / x-tex">CH[C(O)OR^{10}]_2< / annotation>< / semantics>< / com:Math> or azide; where R<com:Sup>10< / com:Sup> and R<com:Sup>11< / com:Sup> are as described above but are suitably each independently H or C<com:Sub>1-10< / com:Sub> alkyl, <com:Math><semantics>C2−10<annotation encoding="application / x-tex">C_{2-10}< / annotation>< / semantics>< / com:Math> alkenyl or <com:Math><semantics>C2−10<annotation encoding="application / x-tex">C_{2-10}< / annotation>< / semantics>< / com:Math> alkynyl optionally substituted as described above or, when <com:Math><semantics>R4<annotation encoding="application / x-tex">R^4< / annotation>< / semantics>< / com:Math> is NR<com:Sup>10< / com:Sup>R<com:Sup>11< / com:Sup>, R<com:Sup>11< / com:Sup> may also suitably be a heteroaryl group such as tetrazole; or when R<com:Sup>4< / com:Sup> is CH(OR<com:Sup>10< / com:Sup>)(OR<com:Sup>11< / com:Sup>), the OR<com:Sup>10< / com:Sup> and OR<com:Sup>11< / com:Sup> groups together with the carbon atom to which they are attached may form a cyclic acetal group, particularly a 1,3-dioxane or 1,3-dioxolane group. In still other particularly suitable compounds R<com:Sup>4< / com:Sup> is NR<com:Sup>10< / com:Sup>C(O)NR<com:Sup>10< / com:Sup>SO<com:Sub>2< / com:Sub>R<com:Sup>11< / com:Sup> or C(O)NR<com:Sup>10< / com:Sup>SO<com:Sub>2< / com:Sub>R<com:Sup>11< / com:Sup>, where R<com:Sup>10< / com:Sup> and R<com:Sup>11< / com:Sup> are as described above but are suitably each independently H or <com:Math><semantics>C1−10<annotation encoding="application / x-tex">C_{1-10}< / annotation>< / semantics>< / com:Math> alkyl, <com:Math><semantics>C2−10<annotation encoding="application / x-tex">C_{2-10}< / annotation>< / semantics>< / com:Math> alkenyl or <com:Math><semantics>C2−10<annotation encoding="application / x-tex">C_{2-10}< / annotation>< / semantics>< / com:Math> alkynyl optionally substituted as described above. In one embodiment, <com:Math><semantics>R4<annotation encoding="application / x-tex">R^4< / annotation>< / semantics>< / com:Math> is <com:Math><semantics>C(O)OR10<annotation encoding="application / x-tex">C(O)OR^{10}< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>OC(O)R10<annotation encoding="application / x-tex">OC(O)R^{10}< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>C(O)NR10R11<annotation encoding="application / x-tex">C(O)NR^{10}R^{11}< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>OR10<annotation encoding="application / x-tex">OR^{10}< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>OSi(R13)3<annotation encoding="application / x-tex">OSi(R^{13})_3< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>S(O)R10<annotation encoding="application / x-tex">S(O)R^{10}< / annotation>< / semantics>< / com:Math>, SO<com:Sub>2< / com:Sub>R<com:Sup>10< / com:Sup>, OSO<com:Sub>2< / com:Sub>R<com:Sup>10< / com:Sup>, SO<com:Sub>3< / com:Sub>R<com:Sup>10< / com:Sup>, OSO<com:Sub>3< / com:Sub>R<com:Sup>10< / com:Sup>, halo, CN, C(O)R<com:Sup>10< / com:Sup>, NR<com:Sup>10< / com:Sup>R<com:Sup>11< / com:Sup>, C(O)CH<com:Sub>2< / com:Sub>N<com:Sub>2< / com:Sub>, <com:Math><semantics>CH[C(O)OR10]2<annotation encoding="application / x-tex">CH[C(O)OR^{10}]_2< / annotation>< / semantics>< / com:Math>, azide, <com:Math><semantics>NO2<annotation encoding="application / x-tex">NO_2< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>NR10C(O)NR10SO2R11<annotation encoding="application / x-tex">NR^{10}C(O)NR^{10}SO_2R^{11}< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>C(O)NR10SO2R11<annotation encoding="application / x-tex">C(O)NR^{10}SO_2R^{11}< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>CH(XR10)(XR11)<annotation encoding="application / x-tex">CH(XR^{10})(XR^{11})< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>CH(R10)(XR11)<annotation encoding="application / x-tex">CH(R^{10})(XR^{11})< / annotation>< / semantics>< / com:Math> or a carboxylic acid mimetic group such as tetrazole. In another embodiment, <com:Math><semantics>R4<annotation encoding="application / x-tex">R^4< / annotation>< / semantics>< / com:Math> is <com:Math><semantics>C(O)OR10<annotation encoding="application / x-tex">C(O)OR^{10}< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>OC(O)R10<annotation encoding="application / x-tex">OC(O)R^{10}< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>C(O)NR10R11<annotation encoding="application / x-tex">C(O)NR^{10}R^{11}< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>OR10<annotation encoding="application / x-tex">OR^{10}< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>OSi(R13)3<annotation encoding="application / x-tex">OSi(R^{13})_3< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>S(O)R10<annotation encoding="application / x-tex">S(O)R^{10}< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>SO2R10<annotation encoding="application / x-tex">SO_2R^{10}< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>OSO2R10<annotation encoding="application / x-tex">OSO_2R^{10}< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>SO3R10<annotation encoding="application / x-tex">SO_3R^{10}< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>OSO3R10<annotation encoding="application / x-tex">OSO_3R^{10}< / annotation>< / semantics>< / com:Math>, halo, <com:Math><semantics>CN<annotation encoding="application / x-tex">CN< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>C(O)R10<annotation encoding="application / x-tex">C(O)R^{10}< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>CH(OR10)(OR11)<annotation encoding="application / x-tex">CH(OR^{10})(OR^{11})< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>CH(R10)(OR11)<annotation encoding="application / x-tex">CH(R^{10})(OR^{11})< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>CH(SR10)(SR11)<annotation encoding="application / x-tex">CH(SR^{10})(SR^{11})< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>NR10R11<annotation encoding="application / x-tex">NR^{10}R^{11}< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>C(O)CH2N2<annotation encoding="application / x-tex">C(O)CH_2N_2< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>CH[C(O)OR10]2<annotation encoding="application / x-tex">CH[C(O)OR^{10}]_2< / annotation>< / semantics>< / com:Math>, azide or a carboxylic acid mimetic group such as tetrazole. In one embodiment, R<com:Sup>4< / com:Sup> is C(O)OR<com:Sup>10< / com:Sup>, CONR<com:Sup>10< / com:Sup>R<com:Sup>11< / com:Sup>, OSO<com:Sub>2< / com:Sub>R<com:Sup>10< / com:Sup>, OSO<com:Sub>3< / com:Sub>R<com:Sup>10< / com:Sup>, CN, azide, OR<com:Sup>10< / com:Sup>, <com:Math><semantics>OSi(R13)3<annotation encoding="application / x-tex">OSi(R^{13})_3< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>CH[C(O)OR10]2<annotation encoding="application / x-tex">CH[C(O)OR^{10}]_2< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>CH(OR10)(OR11)<annotation encoding="application / x-tex">CH(OR^{10})(OR^{11})< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>NR10CONR10SO2R11<annotation encoding="application / x-tex">NR^{10}CONR^{10}SO_2R^{11}< / annotation>< / semantics>< / com:Math> and <com:Math><semantics>NR10SO2R11<annotation encoding="application / x-tex">NR^{10}SO_2R^{11}< / annotation>< / semantics>< / com:Math> and tetrazole. In one embodiment, R<com:Sup>4< / com:Sup> is C(O)OR<com:Sup>10< / com:Sup>, OC(O)R<com:Sup>10< / com:Sup>, OR<com:Sup>10< / com:Sup>, OSi(R<com:Sup>13< / com:Sup>)<com:Sub>3< / com:Sub>, OSO<com:Sub>2< / com:Sub>R<com:Sup>10< / com:Sup>, halo, CN, <com:Math><semantics>C(O)R10<annotation encoding="application / x-tex">C(O)R^{10}< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>NR10R11<annotation encoding="application / x-tex">NR^{10}R^{11}< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>CH[(C(O)OR10)]2<annotation encoding="application / x-tex">CH[(C(O)OR^{10})]_2< / annotation>< / semantics>< / com:Math>, azide, <com:Math><semantics>C(O)NR10SO2R11<annotation encoding="application / x-tex">C(O)NR^{10}SO_2R^{11}< / annotation>< / semantics>< / com:Math> <com:Math><semantics>CH(XR10)(XR11)<annotation encoding="application / x-tex">CH(XR^{10})(XR^{11})< / annotation>< / semantics>< / com:Math>; phthalimide, tetrazole or substituted tetrazole. Other examples of R<com:Sup>4< / com:Sup> groups include azide and tetrazole. In one embodiment, R<com:Sup>5< / com:Sup> is H. In one embodiment, R<com:Sup>5< / com:Sup> is OH. In one embodiment, R<com:Sup>5< / com:Sup> is a protected OH group. In one embodiment, R<com:Sup>5< / com:Sup> is a protected OH group which is not stable in a basic environment such that treatment with a base converts the protected OH group to OH. Examples of such groups are well known in the art and include a group OC(O)R<com:Sup>14< / com:Sup> as defined above in which R<com:Sup>14< / com:Sup> is a group R<com:Sup>10< / com:Sup> as defined above for general formula (Ia) or formula (I). Particularly suitable R<com:Sup>14< / com:Sup> groups are as defined for R<com:Sup>10< / com:Sup> above and include C<com:Sub>1-6< / com:Sub> alkyl such as methyl, or benzyl; or C<com:Sub>1-6< / com:Sub> alkyl such as methyl, or phenyl. In another embodiment, R<com:Sup>5< / com:Sup> is a protected OH group which is stable in a basic environment. Examples of such groups are well known in the art and include OSi(R<com:Sup>16< / com:Sup>)<com:Sub>3< / com:Sub>, where each R<com:Sup>16< / com:Sup> is independently a group R<com:Sup>13< / com:Sup> as defined above for general formulae (la) and (l), and is suitably C<com:Sub>1-6< / com:Sub> alkyl or phenyl. In one embodiment, Si(R<com:Sup>16< / com:Sup>)<com:Sub>3< / com:Sub> is selected from the group consisting of trimethylsilyl (TMS), triethylsilyl (TES), triphenylsilyl (TPS), tri-isopropylsilyl (TIPS), thexyldimethylsilyl (TDS), tert-butyldiphenylsilyl (TBDPS), tert-butyldimethylsilyl (TBDMS or TBS), di-tert-butylmethylsilyl (DTBMS), diethylisopropylsilyl (DEIPS) and dimethylisopropylsilyl (DMIPS), in particular TMS, TES, TIPS, TBDMS and TBDPS. In one aspect of the invention is provided a compound of general formula (Ia) or (I) selected from: (6β, 7β, 22E)-6,7-epoxy-3-oxo-4,22-choladien-24-oic acid ethyl ester (Example 1); (6β, 7β, 20S)-6,7-epoxy-3-oxo-4,22-choladien-24-oic acid ethyl ester (Example 5); (6β, 7β, 20S)-6,7-epoxy-20-hydroxymethyl-pregna-4-en-3-one (Example 41); (6β, 7β, 20S)-6,7-epoxy-20-bromomethyl-pregna-4-en-3-one (Example 42); (20S)-methanesulfonyloxymethyl-6,7-β-epoxy-4-pregnen-3-one (Example 43); (20R)-cyanomethyl-6,7-β-epoxy-4-pregnen-3-one (Example 44); (20S)-20-acetoxymethyl-6,7-β-epoxy-pregna-4-en-3-one (Example 45); (6β, 7β, 20S)-6,7-epoxy-20-tert-butyldiphenylsiloxymethyl-pregna-4-en-3-one (Example 46); (6β, 7β, 20S)-6,7-epoxy-20-azidomethyl-pregna-4-en-3-one (Example 47); (6β, 7β, 20S)-6,7-epoxy-20-(N-phthalimidomethyl)-pregna-4,6-dien-3-one (Example 48); (6β, 7β, 20S)-6,7-epoxy-20-formyl-pregna-4-en-3-one (Example 49); (6β, 7β, 20S)-6,7-epoxy-20-(ethylenedioxymethyl)-pregna-4-en-3-one (Example 50); and (6β, 7β)-6,7-epoxy-3-oxo-4-cholen-23-carboxy-24-oic acid dimethyl ester (Example 51); or a salt or isotopic variant thereof. Preparation of compounds of general formula (Ia) and (I) The epoxidation of dienone (IIA) using <com:Math><semantics>meta<annotation encoding="application / x-tex">meta< / annotation>< / semantics>< / com:Math>-chloroperoxybenzoic acid (<com:Math><semantics>mCPBA<annotation encoding="application / x-tex">mCPBA< / annotation>< / semantics>< / com:Math>) or magnesium monoperoxyphthalate (MMPP) is described by Uekawa et al. in Biosci. Biotechnol. Biochem. 2004, 68, 1332-1337 and is said to yield the alpha-epoxide, as shown in Scheme 1. Scheme 1: Uekawa conditions [Image disponible dans le document PDF, Image available in the PDF document] Starting from this alpha-epoxide, the present inventors have developed processes and intermediates for synthesizing obeticholic acid and analogues thereof as described in patent applications Nos. PCT / GB2015 / 053516 (WO2016 / 079517), PCT / GB2015 / 053517 (WO2016 / 079518), PCT / GB2015 / 053518 (WO2016 / 079519) and PCT / GB2015 / 053519 (WO2016 / 079520). The present inventors have now devised an alternative route to obeticholic acid and its analogues utilising the corresponding beta-epoxide. The inventors investigated further conditions for the epoxidation of compound (IIA) with a view to forming the beta-epoxide, but found that peroxides (such as mCPBA or MMPP – varying the conditions described in Uekawa et al.), dimethyldioxirane (DMDO) and other substituted dioxiranes as well as reactions promoted by various catalysts such as MTO or Mn(II) salts, all produced the alpha-epoxide as a major diastereoisomer. The beta epoxide was observed, but typically in only less than 15% yield. It is known that epoxides may be formed via reaction of an alkene to form a halohydrin, which then undergoes an intramolecular ring closing reaction upon treatment with a base to form an epoxide. Such a reaction is described by Draper, R. W. in J. Chem. Soc. Perkin Trans. I, 1983, 2781-2786 wherein a 4,6-diene-3-one steroid molecule was reacted with chromyl chloride to form (as a sole product) the <com:Math><semantics>6β<annotation encoding="application / x-tex">6\beta< / annotation>< / semantics>< / com:Math>-chloro,<com:Math><semantics>7α<annotation encoding="application / x-tex">7\alpha< / annotation>< / semantics>< / com:Math>-hydrin: [Image disponible dans le document PDF, Image available in the PDF document] However, when treated with base this compound would form the alpha (down) epoxide. The present inventors were therefore surprised to find that by reacting a compound of formula (II) with inexpensive and readily available trichloroisocyanuric acid (TCCA) (literature describing use of TCCA: J. Braz. Chem. Soc. 2002, 13 (5), 700-703; Org. Proc. Res. Dev. 2002, 6 (4), 384-393) the beta-epoxide could be accessed in 40% yield via forming the 6,7-halohydrin compound (IIIxA) or (IIIyA). [Image disponible dans le document PDF, Image available in the PDF document] This reaction is described in Example 1. The halohydrin compound (IIIxA) or (IIIyA) was then cyclized to form the desired beta- epoxide (IA) using a base, 1,8-diazabicycloundec-7-ene (DBU) in 50 % yield. This reaction is described in Example 2. It should be noted that for the cyclisation reaction to form compound (IA) it is not necessary to identify whether (IIIxA) or (IIIyA) was formed, since both compounds will cyclise under basic conditions to form the same compound (IA). Thus, in one aspect of the invention is provided a process for preparing a compound of general formula (la) comprising the steps of: (A) reacting a compound of general formula (IIa) with a halogenating agent to give a compound of general formula (Illxa) and / or a compound of general formula (Illya): [Image disponible dans le document PDF, Image available in the PDF document] wherein X is Cl, Br or I; and wherein Y, R<com:Sup>2< / com:Sup>, R<com:Sup>4< / com:Sup> and R<com:Sup>5< / com:Sup> are as defined for a compound of general formula (Ia); and (B) reacting a compound of general formula (Illxa) and / or a compound of general formula (IIIya) with a base to form a compound of general formula (la): [Image disponible dans le document PDF, Image available in the PDF document] a) wherein X is CI, Br or I; and wherein Y, R<com:Sup>2< / com:Sup>, R<com:Sup>4< / com:Sup> and R<com:Sup>5< / com:Sup> are as defined for a compound of general formula (Ia). In another aspect of the invention is provided a process for preparing a compound of general formula (I) comprising the steps of: (A) reacting a compound of general formula (II) with trichloroisocyanuric acid (TCCA), tribromoisocyanuric acid (TBCA), triiodoisocyanuric acid (TICA), 1,3-dichloro-5,5- dimethylhydantoin (DCDMH), 1,3-dibromo-5,5-dimethylhydantoin (DBDMH), or 1,3- diiodo-5,5-dimethylhydantoin (DIDMH) to give a compound of general formula (IIIx) and / or a compound of general formula (IIIy): [Image disponible dans le document PDF, Image available in the PDF document] (II) (IIIX) (IIIy) wherein X is CI, Br or I; and wherein Y, R<com:Sup>2< / com:Sup>, R<com:Sup>4< / com:Sup> and R<com:Sup>5< / com:Sup> are as defined for a compound of general formula (I); and (B) reacting a compound of general formula (IIIx) and / or a compound of general formula (IIIy) with a base to form a compound of general formula (I): [Image disponible dans le document PDF, Image available in the PDF document] wherein X is CI, Br or I; and wherein Y, R<com:Sup>2< / com:Sup>, R<com:Sup>4< / com:Sup> and R<com:Sup>5< / com:Sup> are as defined for a compound of general formula (I). Suitably, step (B) is carried out using crude halohydrin intermediates obtained from step (A) without further purification. Thus, in one aspect of the invention is provided a process for preparing a compound of general formula (la) comprising: reacting a compound of general formula (IIa) with a halogenating agent followed by reaction with base to give a compound of general formula (la): [Image disponible dans le document PDF, Image available in the PDF document] [Image disponible dans le document PDF, Image available in the PDF document] (lla) (la) wherein Y, R<com:Sup>2< / com:Sup>, R<com:Sup>4< / com:Sup> and R<com:Sup>5< / com:Sup> are as defined for a compound of general formula (Ia) and halogenating agent is as defined above. In another aspect of the invention is provided a process for preparing a compound of general formula (I) comprising: reacting a compound of general formula (II) with trichloroisocyanuric acid (TCCA), tribromoisocyanuric acid (TBCA), triiodoisocyanuric acid (TICA), 1,3-dichloro-5,5- dimethylhydantoin (DCDMH), 1,3-dibromo-5,5-dimethylhydantoin (DBDMH), or 1,3- diiodo-5,5-dimethylhydantoin (DIDMH) followed by reaction with base to give a compound of general formula (I): [Image disponible dans le document PDF, Image available in the PDF document] [Image disponible dans le document PDF, Image available in the PDF document] (II) (I) wherein Y, R<com:Sup>2< / com:Sup>, R<com:Sup>4< / com:Sup> and R<com:Sup>5< / com:Sup> are as defined for a compound of general formula (I). References to step (A) and step (B) below apply whether the halohydrin intermediates are isolated and purified, or not. Suitable halogenating agents are those capable of forming "positive halogen" and include, but are not limited to: Br<com:Sub>2< / com:Sub>, Cl<com:Sub>2< / com:Sub>, l<com:Sub>2< / com:Sub>, N-bromosuccinimide (NBS), N-chlorosuccinimide (NCS), N-iodosuccinimide (NIS), chloramine-T (tosylchloramide), tert-butylhypochlorite, trichloroisocyanuric acid (TCCA), tribromoisocyanuric acid (TBCA), triiodoisocyanuric acid (TICA), 1,3-dichloro-5,5-dimethylhydantoin (DCDMH), 1,3-dibromo-5,5-dimethylhydantoin (DBDMH), or 1,3-diiodo-5,5-dimethylhydantoin (DIDMH). Suitable halogenating agents also include reagents where Br<com:Sub>2< / com:Sub>, Cl<com:Sub>2< / com:Sub> or I<com:Sub>2< / com:Sub> are generated in situ, for example di-tert-butyl peroxide with TiCl<com:Sub>4< / com:Sub>; Ca(OCl)<com:Sub>2< / com:Sub> with NaCl in AcOH; or TMSCl with <com:Math><semantics>H2O2<annotation encoding="application / x-tex">H_2O_2< / annotation>< / semantics>< / com:Math>. Thus, in one embodiment, the halogenating agent is selected from Br<com:Sub>2< / com:Sub>, Cl<com:Sub>2< / com:Sub>, I<com:Sub>2< / com:Sub>, NBS, NCS, NIS, chloramine-T, tert-butylhypochlorite, TCCA, TBCA, TICA, DCDMH, DBDMH, DIDMH, di-tert-butyl peroxide with <com:Math><semantics>TiCl4<annotation encoding="application / x-tex">TiCl_4< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>Ca(OCl)2<annotation encoding="application / x-tex">Ca(OCl)_2< / annotation>< / semantics>< / com:Math> with NaCl in AcOH; or TMSCl with <com:Math><semantics>H2O2<annotation encoding="application / x-tex">H_2O_2< / annotation>< / semantics>< / com:Math>. In particular, the halogenating agent is selected from NBS, NCS, NIS, chloramine-T, TCCA, TBCA, TICA, DCDMH, DBDMH and DIDMH, for example, the halogenating agent is selected from TCCA, TBCA, TICA, DCDMH, DBDMH and DIDMH e.g. is selected from TCCA and tert-butylhypochlorite, in particular TCCA. Tribromoisocyanuric acid (TBCA) and triiodoisocyanuric acid (TICA) are equivalents of trichloroisocyanuric acid (TCCA), and have the following structure: [Image disponible dans le document PDF, Image available in the PDF document] 1,3-Dichloro-5,5-dimethylhydantoin (DCDMH), 1,3-dibromo-5,5-dimethylhydantoin (DBDMH), and 1,3-diiodo-5,5-dimethylhydantoin (DIDMH) have the following structure: [Image disponible dans le document PDF, Image available in the PDF document] In step (A), suitably the compound of general formula (II) is reacted with TCCA, TBCA or TICA, especially TCCA. In one embodiment, in step (A) the compound of general formula (II) is reacted with TCCA, TBCA, TICA or tert-butylhypochlorite, especially TCCA or tert-butylhypochlorite, in particular TCCA. Suitably, 0.1-2.2 equivalents of halogenating agent are used, for example 0.2-1.5, 0.2-0.9, 0.2-0.6 or about 0.4 equivalents. Thus, in one embodiment, in step (A), 0.1-2.2 equivalents of halogenating agent are used, for example 0.2-1.5, 0.2-0.9, 0.2-0.6 or about 0.4 equivalents In step (A), typically 0.1-2.2 equivalents of halogenating agent e.g. TCCA, TBCA, TICA, DCDMH, DBDMH or DIDMH, are used, for example 0.1-0.9, 0.2-0.6 or about 0.4 equivalents. The reaction is suitably carried out in an organic solvent such as acetone, DMF, MeCN or CH<com:Sub>2< / com:Sub>Cl<com:Sub>2< / com:Sub> which may optionally be mixed with a co-solvent such as water and / or an additive such as MeSO<com:Sub>3< / com:Sub>H or benzoic acid. Other suitable organic solvents include THF, t-butyl alcohol, acetic acid, dioxane, DMSO and formic acid. In one embodiment, the reaction is carried out in a solvent selected from acetone, DMF, MeCN or CH<com:Sub>2< / com:Sub>Cl<com:Sub>2< / com:Sub>, THF, t-butyl alcohol, acetic acid, dioxane, DMSO, formic acid and water, and mixtures thereof. In one embodiment, the reaction solvent is a mixture of acetone and water. In one embodiment, the reaction solvent is neat formic acid. In one embodiment, the reaction solvent is neat acetic acid. In one embodiment, the reaction solvent comprises formic acid or acetic acid. In one embodiment, the reaction is carried out in the presence of HOC(O)Rx, HORy, or HSO<com:Sub>3< / com:Sub>R<com:Sup>z< / com:Sup>; wherein R<com:Sup>x< / com:Sup> is H, C<com:Sub>1-4< / com:Sub> alkyl (e.g. methyl or ethyl), phenyl or benzyl; R<com:Sup>y< / com:Sup> is phenyl, benzyl or C<com:Sub>2-4< / com:Sub> alkenyl (e.g. allyl); and R<com:Sup>z< / com:Sup> is CF<com:Sub>3< / com:Sub> wherein phenyl and benzyl are optionally substituted with one or more substituents selected from C<com:Sub>1-4< / com:Sub> alkyl, OC<com:Sub>1-4< / com:Sub> alkyl, halo, nitro, C<com:Sub>1-4< / com:Sub> haloalkyl and OC<com:Sub>1-4< / com:Sub> haloalkyl. In one embodiment, HOR<com:Sup>x< / com:Sup>, HOR<com:Sup>y< / com:Sup> or HSO<com:Sub>3< / com:Sub>R<com:Sup>z< / com:Sup> may be present as an additive in the reaction (suitably in the absence of water and in the presence of an aprotic solvent). In another embodiment, HORx, HORy or HSO<com:Sub>3< / com:Sub>Rz is present as the reaction solvent itself. In embodiments where the reaction is carried out in the presence of HOC(O)R<com:Sup>x< / com:Sup>, HOR<com:Sup>y< / com:Sup>, or HSO<com:Sub>3< / com:Sub>R<com:Sup>z< / com:Sup> as above defined, in the absence of water or a protic solvent, intermediate compounds of formula (IIIxz) and / or intermediate compounds of formula (IIIyz) (as hereinabove defined) will be formed following treatment of the compound of formula (IIa) or (II) with halogenating agent. In circumstances where group R<com:Sup>40< / com:Sup> is not base labile, the process to form the compound of formula (la) or (l) further includes an additional step of removal of the R<com:Sup>40< / com:Sup> group prior to treatment with base. For example, where OR<com:Sup>40< / com:Sup> is Oallyl (formed by reaction of HOR<com:Sup>y< / com:Sup> wherein R<com:Sup>y< / com:Sup> is allyl), the allyl group may be removed by treatment with PdCl<com:Sub>2< / com:Sub>. Such steps to remove group R<com:Sup>40< / com:Sup> are in effect deprotection steps and are well to those of skill in the art (see Wuts, PGM and Greene, TW (2006) "Greene's Protective Groups in Organic Synthesis", 4th Edition, John Wiley & Sons, Inc., Hoboken, NJ, USA). A further example of such a deprotection step is where <com:Math><semantics>OR40<annotation encoding="application / x-tex">OR^{40}< / annotation>< / semantics>< / com:Math> is OPMB (PMB = paramethoxybenzyl, formed by reaction of HOR<com:Sup>y< / com:Sup> wherein R<com:Sup>y< / com:Sup> is paramethoxybenzyl), and the PMB group may be removed using DDQ (2,3-dichloro-5,6-dicyano-p-benzoquinone). Suitably the reaction is carried out at a temperature of between -40 °C and 50 °C, e.g. between 0 °C and room temperature (e.g. 18 °C), or at 0 °C, or at room temperature (e.g. at 18 °C). In one embodiment, step (A) is the reaction of a compound of general formula (IIa) or a compound of general formula (II) with a halogenating agent e.g. TCCA, TBCA, TICA, DCDMH, DBDMH or DIDMH to give a compound of general formula (IIIxa) or a compound of formula (IIIx), respectively. In one embodiment, step (A) is the reaction of a compound of formula (IIa) or a compound of formula (II) with a halogenating agent e.g. TCCA, TBCA, TICA, DCDMH, DBDMH or DIDMH to give a compound of general formula (IIIyx) or a compound of formula (IIIy), respectively. In one embodiment, step (A) is the reaction of a compound of formula (IIa) a compound of formula (II) with a halogenating agent e.g. TCCA, TBCA, TICA, DCDMH, DBDMH or DIDMH to give a mixture of a compound of general formula (IIIxa) and a compound of general formula (IIIya), or a mixture of a compound of general formula (IIIx) and a compound of general formula (IIIy), respectively. In step (B), suitable bases include but are not limited to KOH, NaOH, NaOMe, NaOEt, NaCO<com:Sub>3< / com:Sub>, K<com:Sub>2< / com:Sub>CO<com:Sub>3< / com:Sub> and non-nucleophilic bases such as N,N-diisopropylethylamine (DIPEA), 1,8-diazabicycloundec-7-ene (DBU), and 2,6-di-tert-butylpyridine. Suitably, DBU is in CH<com:Sub>2< / com:Sub>Cl<com:Sub>2< / com:Sub>, NaOEt is in THF and K<com:Sub>2< / com:Sub>CO<com:Sub>3< / com:Sub> is in EtOH or MeOH. Suitable bases would be well known to the skilled person. In one embodiment, the base is DBU. Suitably 1-2 equivalents such as about 1.5 equivalents of base are used in the reaction. In one embodiment, step (B) is the reaction of a compound of general formula (IIIxa) or a compound of formula (IIIx) with a base to give a compound of general formula (Ia) or a compound of general formula (I), respectively. In one embodiment, step (B) is the reaction of a compound of formula (Illya) or a compound of formula (Illy) with a base to give a compound of general formula (la) or a compound of formula (l), respectively. In one embodiment, step (B) is the reaction of a mixture of a compound of formula (IIIxa) and a compound of formula (IIIya), or a mixture of a compound of formula (IIIx) and a compound of formula (IIIy), with a base to give a compound of general formula (Ia) or a compound of formula (I), respectively. The reaction is suitably carried out in an organic solvent such as acetone, DMF, MeCN or CH<com:Sub>2< / com:Sub>Cl<com:Sub>2< / com:Sub> which may optionally be mixed with a co-solvent such as water and / or an additive such as MeSO<com:Sub>3< / com:Sub>H or benzoic acid. Other suitable organic solvents include THF, t-butyl alcohol, acetic acid, dioxane, DMSO, formic acid. In one embodiment, the reaction is carried out in a solvent selected from acetone, DMF, MeCN or CH<com:Sub>2< / com:Sub>Cl<com:Sub>2< / com:Sub>, THF, t-butyl alcohol, acetic acid, dioxane, DMSO, formic acid and water, and mixtures thereof. In one embodiment the reaction solvent is a mixture of acetone and water. In one embodiment, the reaction solvent is neat formic acid. In one embodiment, the reaction solvent is neat acetic acid. Suitably the reaction is carried out at a temperature of between -40 °C and 50 °C, e.g. between 0 °C and room temperature (e.g. 18 °C), or at 0 °C, or at room temperature (e.g. at 18 °C). In one embodiment, is provided a process for preparing a compound of general formula (I) comprising: reacting a compound of general formula (II) with trichloroisocyanuric acid (TCCA) or tert- butylhypochlorite, or DBDMH (in particular trichloroisocyanuric acid (TCCA) or tert- butylhypochlorite) followed by reaction with base to give a compound of general formula (l): [Image disponible dans le document PDF, Image available in the PDF document] wherein Y, R<com:Sup>2< / com:Sup>, R<com:Sup>4< / com:Sup> and R<com:Sup>5< / com:Sup> are as defined for a compound of general formula (I), wherein the reaction is carried out in a solvent selected from acetone, water, formic acid, acetic acid and mixtures thereof, in particular a mixture of acetone and water, neat formic acid or neat acetic acid. In this embodiment, prior to reaction with base the halohydrin intermediate(s) is / are isolated but are not purified. This process for forming the beta-epoxide, in at least some embodiments, is expected to have one or more advantages of: good regio- and stereo-selectivity; simplified procedure; low cost. Preparation of compounds of general formula (IIa) and (II) Compounds of general formula (IIa) or compounds of general formula (II) may be prepared from compounds of general formula (VIIa) or from compounds of general formula (VII), respectively: [Image disponible dans le document PDF, Image available in the PDF document] (VIIa) / (VII) wherein Y, R<com:Sup>2< / com:Sup>, R<com:Sup>4< / com:Sup> and R<com:Sup>5< / com:Sup> and are as defined above for general formula (la) (for formula (VIIa)) or are as above defined for general formula (I) (for formula (VII)); by reaction with an oxidizing agent such as chloranil. The reaction may be carried out under acidic conditions, for example in the presence of acetic acid, and in an organic solvent such as toluene. Some compounds of general formulae (IIa), (II), (VIIa) and (VII) are known. For example Uekawa et al. in Biosci. Biotechnol. Biochem., 2004, 68, 1332-1337 describe the synthesis of (22E)-3-oxo-4,22-choladien-24-oic acid ethyl ester (compound (VIIA)) from stigmasterol followed by its conversion to (22E)-3-oxo-4,6,22-cholatrien-24-oic acid ethyl ester (referred to herein as compound (IIA)), which has the formula: [Image disponible dans le document PDF, Image available in the PDF document] (IIA) Other compounds of general formulae (IIa), (II), (VIIa), and (VII) may be prepared by analogous methods from phytosterols similar to stigmasterol. Stigmasterol and other phytosterols are plant sterols and are readily available or may be prepared by known routes. [Image disponible dans le document PDF, Image available in the PDF document] Compounds of general formula (VIIa) or compounds of general formula (VII) may also be prepared from compounds of general formula (VIIIa) or from compounds of general formula (VIII), respectively: [Image disponible dans le document PDF, Image available in the PDF document] (VIIIa) / (VIII) wherein Y, R<com:Sup>2< / com:Sup>, R<com:Sup>4< / com:Sup> and R<com:Sup>5< / com:Sup> are as defined in general formula (Ia) (for formula (VIIIa)) or are as defined in general formula (I) (for formula (VIII)); by reaction with lithium bromide and a base such as lithium carbonate. The reaction may be carried out in a solvent such as N, N-dimethylformamide (DMF) and at a temperature of about 120 to 180 °C. Such a reaction is described in Example 10 of patent application No. WO2016 / 079517. Compounds of general formula (VIIIa) or compounds of general formula (VIII) may be obtained by bromination of a compound of general formula (IXa), or by bromination of a compound of general formula (IX), respectively: [Image disponible dans le document PDF, Image available in the PDF document] (IXa) / (IX) wherein Y, R<com:Sup>2< / com:Sup>, R<com:Sup>4< / com:Sup> and R<com:Sup>5< / com:Sup> are as defined in general formula (I) (for formula (IXa)) or are as defined in general formula (la) (for formula (lX)); using, for example bromine in acetic acid. Such a reaction is described in Example 9 of patent application No. WO2016 / 079517. Compounds of general formula (IXa) or compounds of general formula (IX) may be prepared from compounds of general formula (XIa) or from compounds of general formula (XI), respectively: [Image disponible dans le document PDF, Image available in the PDF document] wherein Y, R<com:Sup>2< / com:Sup>, R<com:Sup>4< / com:Sup> and R<com:Sup>5< / com:Sup> are as defined in general formula (Ia) (for formula (XIa)) or are as defined in general formula (I) (for formula (XI)); by oxidation, typically with a chromium-based oxidizing agent or with sodium hypochlorite. Such a reaction is described in Example 8 of patent application No. WO2016 / 079517. Compounds of general formula (IXa) and compounds of general formula (IX) in which R4 is <com:Math><semantics>C(O)OR10<annotation encoding="application / x-tex">C(O)OR^{10}< / annotation>< / semantics>< / com:Math>, where <com:Math><semantics>R10<annotation encoding="application / x-tex">R^{10}< / annotation>< / semantics>< / com:Math> is <com:Math><semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics>< / com:Math> alkyl or benzyl, or <com:Math><semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics>< / com:Math> alkyl or phenyl, may be prepared from compounds of general formula (IXa) and from compounds of general formula (IX), respectively, in which R<com:Sup>4< / com:Sup> is C(O)OH by esterification, typically by reaction with an appropriate alcohol under acidic conditions. Compounds of general formula (XIa) and compounds of general formula (XI) in which R4 is C(O)OH and R<com:Sup>5< / com:Sup> is H may be prepared from compounds of general formula (XIIa) and from compounds of general formula (XII), respectively: [Image disponible dans le document PDF, Image available in the PDF document] (XIIa) / (XII) wherein R<com:Sup>2< / com:Sup> and Y are as defined in general formula (la) (for formula (XIIa)) and are as defined in general formula (I) (for formula (XII)); <com:Math><semantics>R4<annotation encoding="application / x-tex">R^4< / annotation>< / semantics>< / com:Math> is C(O)OR<com:Sup>10< / com:Sup>, where R<com:Sup>10< / com:Sup> is C<com:Sub>1-6< / com:Sub> alkyl or benzyl; and OR<com:Sup>12< / com:Sup> is a protected OH; by reaction with a reducing agent, typically hydrazine, under basic conditions and in an alcoholic or glycolic solvent, for example diethylene glycol. Where OR<com:Sup>12< / com:Sup> is a protected OH group which is stable under basic conditions, the reaction may be followed by a reaction to remove the protecting group R<com:Sup>12< / com:Sup> to leave an OH group. Protecting groups for OH are discussed above and, for example, R<com:Sup>12< / com:Sup> may be a group C(O)R<com:Sup>14< / com:Sup>, where R<com:Sup>14< / com:Sup> is as defined above, in particular, C<com:Sub>1-6< / com:Sub> alkyl or benzyl; or C<com:Sub>1-6< / com:Sub> alkyl or phenyl. Silyl ethers are also suitable, and in this case, R<com:Sup>12< / com:Sup> may be a group Si(R<com:Sup>16< / com:Sup>)<com:Sub>3< / com:Sub>, where each R<com:Sup>16< / com:Sup> is independently a group R<com:Sup>13< / com:Sup> as defined above but is especially C<com:Sub>1-6< / com:Sub> alkyl or phenyl. Other suitable protecting groups for OH are well known to those of skill in the art (see Wuts, PGM and Greene, TW (2006) "Greene's Protective Groups in Organic Synthesis", 4th Edition, John Wiley & Sons, Inc., Hoboken, NJ, USA). Particularly suitable R<com:Sup>12< / com:Sup> groups include groups which are not stable in the presence of a base since this removes the need for the additional step of removing the protecting group. An example of a group R<com:Sup>12< / com:Sup> which is not stable in basic conditions is a group C(O)R<com:Sup>14< / com:Sup>, where R<com:Sup>14< / com:Sup> is as defined above, and is particularly C<com:Sub>1-6< / com:Sub> alkyl or benzyl, or C<com:Sub>1-6< / com:Sub> alkyl or phenyl. Alternatively, the reaction may be carried out in 2 steps such that the compound of general formula (XIIa) or a compound of formula (XII) is reacted with a compound of general formula (XXXII): [Image disponible dans le document PDF, Image available in the PDF document] (XXXII) wherein R<com:Sup>20< / com:Sup> is a leaving group such as toluene sulfonyl or methane sulfonyl; to give a compound of general formula (XXXIIIa) or a compound of general formula (XXXIII), respectively: [Image disponible dans le document PDF, Image available in the PDF document] (XXXIIIa) / (XXXIII) wherein R<com:Sup>2< / com:Sup> and Y are as defined in general formula (Ia); R<com:Sup>4< / com:Sup> and R<com:Sup>12< / com:Sup> are as defined for general formula (XIIa); and R<com:Sup>20< / com:Sup> is as defined for general formula (XXXII); (all for formula (XXXIIIa)); or wherein R<com:Sup>2< / com:Sup> and Y are as defined in general formula (I); R<com:Sup>4< / com:Sup> and R<com:Sup>12< / com:Sup> are as defined for general formula (VII); and R<com:Sup>20< / com:Sup> is as defined for general formula (XXXII) (all for formula (XXXIII)); followed by reduction with a suitable reducing agent. Examples of reducing agents which can be used in this reaction include hydrides such as sodium borohydride, sodium cyanoborohydride, lithium aluminum hydride etc. In general formula (XXXIIIa) and in general formula (XXXIII) R<com:Sup>20< / com:Sup> is as defined above for compounds of general formula (XXXII) and Y, R<com:Sup>2< / com:Sup>, R<com:Sup>4< / com:Sup> and R<com:Sup>12< / com:Sup> are as defined above for compounds of general formula (XIIa) and for compounds of general formula (XII), respectively. Compounds of general formula (XIIa) or compounds of general formula (XII) may be prepared from compounds of general formula (XIIIa) or from compounds of general formula (XIII), respectively: [Image disponible dans le document PDF, Image available in the PDF document] (XIIIa) / (XIII) wherein R<com:Sup>2< / com:Sup> and Y are as defined in general formula (la) (for formula (XIIIa)) or are as defined in general formula (I) (for formula (XIII)); <com:Math><semantics>R4<annotation encoding="application / x-tex">R^4< / annotation>< / semantics>< / com:Math> is C(O)OR<com:Sup>10< / com:Sup>, where R<com:Sup>10< / com:Sup> is C<com:Sub>1-6< / com:Sub> alkyl or benzyl; and R<com:Sup>12< / com:Sup> is as defined above for general formula (XIIa) (for formula (XIIIa)) or is as defined above for general formula (XXII) (for formula (XIII); and is suitably -C(O)C<com:Sub>1-6< / com:Sub> alkyl; by reaction with an oxidizing agent, for example sodium hypochlorite. Such a reaction is described in Example 5 of patent application No. WO2016 / 079517. The reaction may be carried out under acidic conditions, for example in the presence of acetic acid, and in an organic solvent such as ethyl acetate. Compounds of general formula (XIIIa) or compounds of general formula (XIII) may be prepared from compounds of general formula (XIVa) or from compounds of general formula (XIV), respectively: [Image disponible dans le document PDF, Image available in the PDF document] (XIVa) / (XIV) wherein R<com:Sup>2< / com:Sup> and Y are as defined in general formula (la) (for formula (XIVa)) or are as defined in general formula (I) (for formula (XIV)); <com:Math><semantics>R4<annotation encoding="application / x-tex">R^4< / annotation>< / semantics>< / com:Math> is C(O)OR<com:Sup>10< / com:Sup>, where <com:Math><semantics>R10<annotation encoding="application / x-tex">R^{10}< / annotation>< / semantics>< / com:Math> is C<com:Sub>1-6< / com:Sub> alkyl or benzyl; by reaction with an agent suitable to introduce the protecting group R<com:Sup>12< / com:Sup>. For example, when R<com:Sup>12< / com:Sup> is C(O)R<com:Sup>14< / com:Sup>, the compound of general formula (XIXa) or the compound of general formula (XIX) may be reacted with a carboxylic acid anhydride or an acid chloride in the presence of a weak base such as pyridine, suitably catalysed by 4-dimethylaminopyridine (DMAP). The reaction may be conducted in a solvent such as ethyl acetate. Such a reaction is described in Example 5 of patent application No. WO2016 / 079517. Compounds of general formula (XIVa) or compounds of general formula (XIV) may be prepared by the esterification of compounds of general formula (XVa) or of compounds of general formula (XV), respectively: [Image disponible dans le document PDF, Image available in the PDF document] wherein R<com:Sup>2< / com:Sup> and Y are as defined in general formula (Ia) and general formula (I). The esterification reaction may be carried out by reacting the acid of general formula (XVa) or of general formula (XV) with a suitable alcohol under acidic conditions. Such a reaction is described in Example 5 of patent application No. PCT / GB2015 / 053516. Compounds of general formula (XVa) and of general formula (XV) are known. For example, the compound of general formula (XVa) or of general formula (XV) in which Y is -CH<com:Sub>2< / com:Sub>CH<com:Sub>2< / com:Sub>- and R<com:Sup>2< / com:Sup> is H is deoxycholic acid (referred to herein as compound (XVA)), which is readily available from a number of sources. [Image disponible dans le document PDF, Image available in the PDF document] An alternative route to compounds of general formula (VIIa) and to compounds of general formula (VII) in which the group at the R4 position is an ester is as shown in Scheme 2 in which 4-androstenedione is converted to a compound of general formula (VIIa) or of general formula (VII) in which R<com:Sup>2< / com:Sup> and R<com:Sup>5< / com:Sup> are H; R<com:Sup>4< / com:Sup> is -C(O)OCH<com:Sub>3< / com:Sub> and Y is either -CH<com:Sub>2< / com:Sub>CH<com:Sub>2< / com:Sub>- or -CH=CH-. Scheme 2 [Image disponible dans le document PDF, Image available in the PDF document] 1 Marker et al, J. Am. Chem. Soc., 1940, 62, 2537 Other compounds with different values for Y and R<com:Sup>2< / com:Sup> can be used as alternative starting materials. An alternative route to compounds of general formula (IIa) and to compounds of general formula (II) in which Y is an alkenylene group is by use of an olefination reaction, for example a Horner-Wadsworth-Emmons (HWE) olefination of a compound of general formula (XVIa) or of a compound of general formula (XVI), respectively: [Image disponible dans le document PDF, Image available in the PDF document] (XVIa) / (XVI) wherein R<com:Sup>2< / com:Sup> and R<com:Sup>5< / com:Sup> are as defined for general formula (Ia) and for general formula (I); using a compound of general formula (XVII): [Image disponible dans le document PDF, Image available in the PDF document] wherein R<com:Sup>10< / com:Sup> is as defined for general formula (I). The reaction may be carried out under standard HWE conditions, for example using a base such as sodium hydride. Alternatively, an HWE olefination may be used to convert a compound of formula (XI), (IX), (VIII), (VII) and (II).in which R<com:Sup>4< / com:Sup> is C(O)H to a compound in which Y is an alkenylene group. Compounds of general formula (XVII) are readily available or may be prepared by methods known to those of skill in the art. Other olefination reactions, such as Tebbe olefination, Wittig type olefination or a Julia- Kocienski olefination, would also give rise to compounds of general formula (IIa) and to compounds of formula (II) in which Y is an alkenylene group. These olefination reactions are familiar to a chemist of skill in the art. Compounds of general formula (XVIa) or compounds of general formula (XVI) may be prepared by reaction of a compound of general formula (XVIIIa) or a compound of general formula (XVIII), respectively, with ozone [Image disponible dans le document PDF, Image available in the PDF document] (XVIIIa) / (XVIII) wherein R<com:Sup>2< / com:Sup> and R<com:Sup>5< / com:Sup> are as defined for general formula (la) and for general formula (l) and R<com:Sup>15< / com:Sup> is C<com:Sub>1-6< / com:Sub> alkyl. An example of a reaction of this type is given in patent US 2,624,748A (Levin et al.). Compounds of general formula (XVIIIa) or compound of general formula (XVIII) may be prepared by reaction of a compound of general formula (XIXa) or a compound of general formula (XIX), respectively: [Image disponible dans le document PDF, Image available in the PDF document] (XIXa) / (XIX) wherein R<com:Sup>2< / com:Sup> and R<com:Sup>5< / com:Sup> are as defined for general formula (Ia) and general formula (I), and R<com:Sup>15< / com:Sup> is C<com:Sub>1-6< / com:Sub> alkyl, with an acid in a solvent such as methanol. Compounds of general formula (XIXa) or compounds of general formula (XIX) may be prepared by oxidation of a compound of general formula (XXa) or a compound of general formula (XX), respectively: [Image disponible dans le document PDF, Image available in the PDF document] (XXa) / (XX) wherein R<com:Sup>2< / com:Sup> and R<com:Sup>5< / com:Sup> are as defined for general formula (Ia) and for general formula (I), and R<com:Sup>15< / com:Sup> is C<com:Sub>1-6< / com:Sub> alkyl, using an Oppenauer oxidation. Examples of the conversion of compounds of general formula (XXa) to compounds of general formula (XVIIIa) and of the conversion of compounds of general formula (XX) to compounds of general formula (XX) are taught by Shepherd et al, J. Am. Chem. Soc. 1955, 77, 1212-1215 and Goldstein, J. Med. Chem. 1996, 39, 5092-5099. One example of a compound of general formula (XXa) and of general formula (XX) is ergosterol (referred to herein as (XXA)), which is a fungal sterol and Scheme 3 below shows the conversion of ergosterol to a compound of general formula (II) in which both R<com:Sup>2< / com:Sup> and R<com:Sup>5< / com:Sup> are H, Y is CH=CH<com:Sub>2< / com:Sub> and R<com:Sup>4< / com:Sup> is C(O)OR<com:Sup>10< / com:Sup>, where R<com:Sup>10< / com:Sup> is ethyl. Scheme 3 [Image disponible dans le document PDF, Image available in the PDF document] 20 Compounds of general formula (Ia) and (IIa) and compounds of general formula (I) and (II) in which R<com:Sup>4< / com:Sup> is C(O)R<com:Sup>10< / com:Sup>, C(O)NR<com:Sup>10< / com:Sup>R<com:Sup>11< / com:Sup>, S(O)R<com:Sup>10< / com:Sup>, SO<com:Sub>3< / com:Sub>R<com:Sup>10< / com:Sup>, or OSO<com:Sub>3< / com:Sub>R<com:Sup>10< / com:Sup> may be prepared from the corresponding compounds in which R<com:Sup>4< / com:Sup> is C(O)OR<com:Sup>10< / com:Sup> by reaction with an appropriate reagents using methods well known to those of skill in the art. For example, the methods described in WO2008 / 002573 and WO2010 / 014836 or methods similar to those described by Classon et al, J. Org. Chem., 1988, 53, 6126-6130 and Festa et al, J. Med. Chem., 2014, 57, 8477–8495. Subsequent reactions of compounds of general formula (IA) and (I) Process to form obeticholic acid and obeticholic acid analogues from a compound of general formula (la) and general formula (l) Compounds of general formula (Ia) and of general formula (I) are of use in the synthesis of compounds of general formula (Xa) and of compounds of general formula (X), respectively: [Image disponible dans le document PDF, Image available in the PDF document] (Xa) / (X) or a salt or an isotopic variant thereof; wherein, <com:Math><semantics>R1<annotation encoding="application / x-tex">R^1< / annotation>< / semantics>< / com:Math> is <com:Math><semantics>C1−4<annotation encoding="application / x-tex">C_{1-4}< / annotation>< / semantics>< / com:Math> alkyl, <com:Math><semantics>C2−4<annotation encoding="application / x-tex">C_{2-4}< / annotation>< / semantics>< / com:Math> alkenyl or <com:Math><semantics>C2−4<annotation encoding="application / x-tex">C_{2-4}< / annotation>< / semantics>< / com:Math> alkynyl optionally substituted with one or more substituents selected from halo, OR<com:Sup>6< / com:Sup> and NR<com:Sup>6< / com:Sup>R<com:Sup>7< / com:Sup> (for formula (Xa); or R<com:Sup>1< / com:Sup> is C<com:Sub>1-4< / com:Sub> alkyl optionally substituted with one or more substituents selected from halo, OR<com:Sup>6< / com:Sup> and <com:Math><semantics>NR6R7<annotation encoding="application / x-tex">NR^6R^7< / annotation>< / semantics>< / com:Math> (for formula (X)); wherein each of <com:Math><semantics>R6<annotation encoding="application / x-tex">R^6< / annotation>< / semantics>< / com:Math> and <com:Math><semantics>R7<annotation encoding="application / x-tex">R^7< / annotation>< / semantics>< / com:Math> is independently H or <com:Math><semantics>C1−4<annotation encoding="application / x-tex">C_{1-4}< / annotation>< / semantics>< / com:Math> alkyl; R<com:Sup>2< / com:Sup> is H, halo or OH; and Y<com:Sup>1< / com:Sup> is a bond, or a C<com:Sub>1-20< / com:Sub> alkylene linker group which is optionally substituted with one or more R<com:Sup>3< / com:Sup>; or Y<com:Sup>1< / com:Sup> and R<com:Sup>4< / com:Sup> together form a =CH<com:Sub>2< / com:Sub> group; R<com:Sup>5a< / com:Sup> is H or OH; wherein R<com:Sup>3< / com:Sup> and R<com:Sup>4< / com:Sup> are as described above for a compound of general formula (Ia) (for formula (Xa)) or are as described above for a compound of general formula (I) (for formula (X)). Compounds of general formula (Xa) and of formula (X) are potent agonists of FXR and TGR5 and include obeticholic acid, which is a compound of formulae (Xa) and (X) in which <com:Math><semantics>R1<annotation encoding="application / x-tex">R^1< / annotation>< / semantics>< / com:Math> is ethyl, <com:Math><semantics>R2<annotation encoding="application / x-tex">R^2< / annotation>< / semantics>< / com:Math> and <com:Math><semantics>R5a<annotation encoding="application / x-tex">R^{5a}< / annotation>< / semantics>< / com:Math> are both H, <com:Math><semantics>Y1<annotation encoding="application / x-tex">Y^1< / annotation>< / semantics>< / com:Math> is -CH<com:Sub>2< / com:Sub>CH<com:Sub>2< / com:Sub>-, and <com:Math><semantics>R4<annotation encoding="application / x-tex">R^4< / annotation>< / semantics>< / com:Math> is C(O)OH. The compounds of general formula (la) or compounds of general formula (l) may be converted to the compounds of general formula (Xa) or compounds of general formula (X), respectively, in a 4 step process via intermediates of general formulae (IVa), (IV), (Va), (V), (VIa) and (VI) as described below. In one aspect of the invention is provided a process for preparing a compound of general formula (Xa) from a compound of formula (la): [Image disponible dans le document PDF, Image available in the PDF document] the process comprising the steps of: (a) selective alkylation of a compound of general formula (la) with an organometallic regent to give a compound of general formula (IVa): [Image disponible dans le document PDF, Image available in the PDF document] (IVa) wherein R<com:Sup>1< / com:Sup> is as defined for a compound of formula (Xa); and Y, R<com:Sup>2< / com:Sup>, R<com:Sup>4< / com:Sup> and R<com:Sup>5< / com:Sup> are as defined for a compound of general formula (Ia); (b) reducing the compound of general formula (IVa) using a suitable reducing agent to give a compound of general formula (Va): [Image disponible dans le document PDF, Image available in the PDF document] (Va) wherein R<com:Sup>1< / com:Sup> and Y<com:Sup>1< / com:Sup> are as defined for a compound of formula (Xa); and R<com:Sup>2< / com:Sup>, R<com:Sup>4< / com:Sup> and R<com:Sup>5< / com:Sup> are as defined for a compound of general formula (Ia); (c) oxidising the compound of general formula (Va) using a suitable oxidising agent to give a compound of general formula (VIa): [Image disponible dans le document PDF, Image available in the PDF document] (Vla) wherein R<com:Sup>1< / com:Sup> and Y<com:Sup>1< / com:Sup> are as defined for a compound of formula (Xa); and R<com:Sup>2< / com:Sup>, R<com:Sup>4< / com:Sup> and R<com:Sup>5< / com:Sup> are as defined for a compound of general formula (Ia); (d) reduction of the compound of general formula (VIa) using a suitable reducing agent and, where R<com:Sup>2< / com:Sup> and / or R<com:Sup>5< / com:Sup> is a protected OH, removal of the protecting group(s), to give a compound of general formula (Xa) as defined above, wherein removal of the protecting group can take place before or after the reduction; and wherein the process further includes one or more optional steps of converting compounds of general formulae (Ia), (IVa), (Va), (VIa), and (Xa) to other compounds of general formulae (Ia), (IVa), (Va), (VIa), and (Xa). The optional steps consist of reacting the side chains of the compounds of general formulae (Ia), (IVa), (Va), (VIa), and (Xa) as described below to arrive at compounds with alternative Y and / or R<com:Sup>4< / com:Sup> moieties. In another aspect of the invention is provided a process for preparing a compound of general formula (X) from a compound of formula (I): [Image disponible dans le document PDF, Image available in the PDF document] the process comprising the steps of: (a) selective alkylation of a compound of general formula (I) with an organometallic regent to give a compound of general formula (IV): [Image disponible dans le document PDF, Image available in the PDF document] (IV) wherein R<com:Sup>1< / com:Sup> is as defined for a compound of formula (X); and Y, R<com:Sup>2< / com:Sup>, R<com:Sup>4< / com:Sup> and R<com:Sup>5< / com:Sup> are as defined for a compound of general formula (I); (b) reducing the compound of general formula (IV) using a suitable reducing agent to give a compound of general formula (V): [Image disponible dans le document PDF, Image available in the PDF document] (V) wherein <com:Math><semantics>R1<annotation encoding="application / x-tex">R^1< / annotation>< / semantics>< / com:Math> and <com:Math><semantics>Y1<annotation encoding="application / x-tex">Y^1< / annotation>< / semantics>< / com:Math> are as defined for a compound of formula (X); and R<com:Sup>2< / com:Sup>, R<com:Sup>4< / com:Sup> and R<com:Sup>5< / com:Sup> are as defined for a compound of general formula (I); (c) oxidising the compound of general formula (V) using a suitable oxidising agent to give a compound of general formula (VI): [Image disponible dans le document PDF, Image available in the PDF document] (VI) wherein <com:Math><semantics>R1<annotation encoding="application / x-tex">R^1< / annotation>< / semantics>< / com:Math> and <com:Math><semantics>Y1<annotation encoding="application / x-tex">Y^1< / annotation>< / semantics>< / com:Math> are as defined for a compound of formula (X); and R<com:Sup>2< / com:Sup>, R<com:Sup>4< / com:Sup> and R<com:Sup>5< / com:Sup> are as defined for a compound of general formula (I); (d) reduction of the compound of general formula (VI) using a suitable reducing agent and, where R<com:Sup>2< / com:Sup> and / or R<com:Sup>5< / com:Sup> is a protected OH, removal of the protecting group(s), to give a compound of general formula (X) as defined above, wherein removal of the protecting group can take place before or after the reduction; and wherein the process further includes one or more optional steps of converting compounds of general formulae (I), (IV), (V), (VI), and (X) to other compounds of general formulae (I), (IV), (V), (VI), and (X). The optional steps consist of reacting the side chains of the compounds of general formulae (I), (IV), (V), (VI), and (X) as described below to arrive at compounds with alternative Y and / or R<com:Sup>4< / com:Sup> moieties. An example of step (a) is shown in Example 6, and example of step (b) in shown in Example 7, and an example of step (c) is shown in Example 8. In one embodiment is provided a compound of general formula (IVa): [Image disponible dans le document PDF, Image available in the PDF document] (IVa) wherein R<com:Sup>1< / com:Sup> is as defined for a compound of formula (Xa); and Y, R<com:Sup>2< / com:Sup>, R<com:Sup>4< / com:Sup> and R<com:Sup>5< / com:Sup> are as defined for a compound of general formula (la). In the compound of general formula (IVa) suitably R<com:Sup>4< / com:Sup> is C(O)OR<com:Sup>10< / com:Sup>, CONR<com:Sup>10< / com:Sup>R<com:Sup>11< / com:Sup>, OSO<com:Sub>2< / com:Sub>R<com:Sup>10< / com:Sup>, <com:Math><semantics>OSO3R10<annotation encoding="application / x-tex">OSO_3R^{10}< / annotation>< / semantics>< / com:Math>, CN, azide, <com:Math><semantics>OR10<annotation encoding="application / x-tex">OR^{10}< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>OSi(R13)3<annotation encoding="application / x-tex">OSi(R^{13})_3< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>CH[C(O)OR10]2<annotation encoding="application / x-tex">CH[C(O)OR^{10}]_2< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>CH(OR10)(OR11)<annotation encoding="application / x-tex">CH(OR^{10})(OR^{11})< / annotation>< / semantics>< / com:Math>, NR<com:Sup>10< / com:Sup>CONR<com:Sup>10< / com:Sup>SO<com:Sub>2< / com:Sub>R<com:Sup>11< / com:Sup>, NR<com:Sup>10< / com:Sup>SO<com:Sub>2< / com:Sub>R<com:Sup>11< / com:Sup> or tetrazole. In one embodiment is provided a compound of general formula (Va): [Image disponible dans le document PDF, Image available in the PDF document] (Va) wherein R<com:Sup>1< / com:Sup> and Y<com:Sup>1< / com:Sup> are as defined for a compound of formula (Xa); and R<com:Sup>2< / com:Sup>, R<com:Sup>4< / com:Sup> and R<com:Sup>5< / com:Sup> are as defined for a compound of general formula (Ia). In the compound of general formula (Va) suitably R<com:Sup>4< / com:Sup> is C(O)OR<com:Sup>10< / com:Sup>, CONR<com:Sup>10< / com:Sup>R<com:Sup>11< / com:Sup>, OSO<com:Sub>2< / com:Sub>R<com:Sup>10< / com:Sup>, OSO<com:Sub>3< / com:Sub>R<com:Sup>10< / com:Sup>, CN, azide, <com:Math><semantics>OR10<annotation encoding="application / x-tex">OR^{10}< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>OSi(R13)3<annotation encoding="application / x-tex">OSi(R^{13})_3< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>CH[C(O)OR10]2<annotation encoding="application / x-tex">CH[C(O)OR^{10}]_2< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>CH(OR10)(OR11)<annotation encoding="application / x-tex">CH(OR^{10})(OR^{11})< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>NR10CONR10SO2R11<annotation encoding="application / x-tex">NR^{10}CONR^{10}SO_2R^{11}< / annotation>< / semantics>< / com:Math>, NR<com:Sup>10< / com:Sup>SO<com:Sub>2< / com:Sub>R<com:Sup>11< / com:Sup> or tetrazole. <com:Math><semantics>(5β,6α,7β)<annotation encoding="application / x-tex">(5\beta, 6\alpha, 7\beta)< / annotation>< / semantics>< / com:Math>-6-ethyl-7-hydroxy-3-oxo-cholan-24-oic acid ethyl ester (a compound of formula (V) / (Va) prepared as described above (steps (a) and (b)) may be used in the synthesis of <com:Math><semantics>(3α,5β,6α,7β)<annotation encoding="application / x-tex">(3\alpha, 5\beta, 6\alpha, 7\beta)< / annotation>< / semantics>< / com:Math>-6-ethyl-3,7-dihydroxy-cholan-24-oic acid, the 7-beta-hydroxy isomer of obeticholic acid (OCA). This is described in Example 21. Compounds of general formula (Xa) and of general formula (X) are potent agonists of FXR and TGR5 and include, in particular, compounds in which R1 is ethyl. Also included are the following. • Compounds in which R<com:Sup>4< / com:Sup> is C(O)OH, for example: obeticholic acid, which is a compound of formula (Xa) / (X) in which R<com:Sup>1< / com:Sup> is ethyl, R<com:Sup>2< / com:Sup> and R<com:Sup>5a< / com:Sup> are both H, Y<com:Sup>1< / com:Sup> is -CH<com:Sub>2< / com:Sub>CH<com:Sub>2< / com:Sub>-, and R<com:Sup>4< / com:Sup> is C(O)OH; and the compound of formula (Xa) / (X) in which R<com:Sup>1< / com:Sup> is ethyl, R<com:Sup>2< / com:Sup> and R<com:Sup>5a< / com:Sup> are both H, <com:Math><semantics>Y1<annotation encoding="application / x-tex">Y^1< / annotation>< / semantics>< / com:Math> is <com:Math><semantics>−CH2CH(CH3)<annotation encoding="application / x-tex">-CH_2CH(CH_3)< / annotation>< / semantics>< / com:Math>-, and <com:Math><semantics>R4<annotation encoding="application / x-tex">R^4< / annotation>< / semantics>< / com:Math> is <com:Math><semantics>C(O)OH<annotation encoding="application / x-tex">C(O)OH< / annotation>< / semantics>< / com:Math>; and the compound of formula (Xa) / (X) in which R<com:Sup>1< / com:Sup> is ethyl, R<com:Sup>2< / com:Sup> is H, R<com:Sup>5a< / com:Sup> is OH, <com:Math><semantics>Y1<annotation encoding="application / x-tex">Y^1< / annotation>< / semantics>< / com:Math> is -CH<com:Sub>2< / com:Sub>CH(CH<com:Sub>3< / com:Sub>)-, and <com:Math><semantics>R4<annotation encoding="application / x-tex">R^4< / annotation>< / semantics>< / com:Math> is C(O)OH. Compounds in which R<com:Sup>4< / com:Sup> is OSO<com:Sub>3< / com:Sub>H or a salt thereof, for example: the compound of formula (Xa) / (X) in which R<com:Sup>1< / com:Sup> is ethyl, R<com:Sup>2< / com:Sup> and R<com:Sup>5a< / com:Sup> are both H, Y<com:Sup>1< / com:Sup> is -CH<com:Sub>2< / com:Sub>CH<com:Sub>2< / com:Sub>-, and R<com:Sup>4< / com:Sup> is OSO<com:Sub>3< / com:Sub>H or a salt thereof; and the compound of formula (Xa) / (X) in which R1 is ethyl, R2 is H, R5a is OH, Y<com:Sup>1< / com:Sup> is -CH<com:Sub>2< / com:Sub>CH<com:Sub>2< / com:Sub>CH<com:Sub>2< / com:Sub>-, and R<com:Sup>4< / com:Sup> is OSO<com:Sub>3< / com:Sub>H or a salt thereof; and the compound of formula (Xa) / (X) in which R<com:Sup>1< / com:Sup> is ethyl, R<com:Sup>2< / com:Sup> is OH, R<com:Sup>5a< / com:Sup> is H, Y<com:Sup>1< / com:Sup> is -CH<com:Sub>2< / com:Sub>CH<com:Sub>2< / com:Sub>-, and R<com:Sub>4< / com:Sub> is OSO<com:Sub>3< / com:Sub>H or a salt thereof. In the compounds of general formulae (Ia), (Xa), (IVa), (Va) and (VIa) and of general formula (I), (X), (IV), (V) and (VI), more suitable values for R<com:Sup>4< / com:Sup> are as defined for general formula (Ia) and general formula (I), respectively. In some compounds of general formulae (Xa), (Va) and (Vla) or of general formulae (X), (V) and (VI), Y<com:Sup>1< / com:Sup> is a bond. In other compounds of general formulae (Xa), (Va) and (Vla) or of general formulae (X), (V) and (VI), Y<com:Sup>1< / com:Sup> is a C<com:Sub>1-15< / com:Sub> alkylene linker group, more suitably C<com:Sub>1-12< / com:Sub>, C<com:Sub>1-10< / com:Sub> or C<com:Sub>1-8< / com:Sub> alkylene linker group and optionally substituted with one or more R<com:Sup>3< / com:Sup> as defined above. Typically each R³ is independently halo, OR8 or NR8R9; where each of R8 and R9 is independently selected from H, methyl or ethyl, especially H or methyl. In some suitable compounds of general formulae (Xa), (Va) and (Vla) or of general formulae (X), (V) and (VI), <com:Math><semantics>Y1<annotation encoding="application / x-tex">Y^1< / annotation>< / semantics>< / com:Math> is an unsubstituted <com:Math><semantics>C1−15<annotation encoding="application / x-tex">C_{1-15}< / annotation>< / semantics>< / com:Math> alkylene or <com:Math><semantics>C2−15<annotation encoding="application / x-tex">C_{2-15}< / annotation>< / semantics>< / com:Math> alkenylene linker, more suitably C<com:Sub>1-12< / com:Sub> alkylene, C<com:Sub>1-10< / com:Sub> alkylnene or C<com:Sub>1-8< / com:Sub> alkylene, or C<com:Sub>2-12< / com:Sub> alkenylene, C<com:Sub>1-10< / com:Sub> alkenylnene or C<com:Sub>1-8< / com:Sub> alkenylene. In suitable compounds of general formulae (Ia), (Xa), (IVa), (Va) and (VIa) or of general formulae (I), (X), (IV), (V) and (VI), <com:Math><semantics>R1<annotation encoding="application / x-tex">R^1< / annotation>< / semantics>< / com:Math> may be <com:Math><semantics>C1−4<annotation encoding="application / x-tex">C_{1-4}< / annotation>< / semantics>< / com:Math> alkyl optionally substituted with one or more substituents selected from halo, OR<com:Sup>6< / com:Sup> or NR<com:Sup>6< / com:Sup>R<com:Sup>7< / com:Sup>, where R<com:Sup>6< / com:Sup> and R<com:Sup>7< / com:Sup> are each independently H, methyl or ethyl, especially H or methyl. More suitably, R<com:Sup>1< / com:Sup> is unsubstituted C<com:Sub>1-4< / com:Sub> alkyl. Step (a) Compounds of general formula (IVa) may be prepared from compounds of general formula (la): [Image disponible dans le document PDF, Image available in the PDF document] (la) wherein R<com:Sup>2< / com:Sup>, R<com:Sup>4< / com:Sup>, R<com:Sup>5< / com:Sup> and Y are as defined above; by selective alkylation with an organometallic reagent, to give a compound of formula: [Image disponible dans le document PDF, Image available in the PDF document] (IVa) Suitably, the compound of general formula (Ia) is [Image disponible dans le document PDF, Image available in the PDF document] (la) wherein <com:Math><semantics>R2<annotation encoding="application / x-tex">R^2< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>R4<annotation encoding="application / x-tex">R^4< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>R5<annotation encoding="application / x-tex">R^5< / annotation>< / semantics>< / com:Math> and Y are as defined above. Compounds of general formula (IV) may be prepared from compounds of general formula (l): [Image disponible dans le document PDF, Image available in the PDF document] (1) wherein R<com:Sup>2< / com:Sup>, R<com:Sup>4< / com:Sup>, R<com:Sup>5< / com:Sup> and Y are as defined above; by selective alkylation with an organometallic reagent, to give a compound of formula: [Image disponible dans le document PDF, Image available in the PDF document] (IV). Suitably, the compound of general formula (I) is [Image disponible dans le document PDF, Image available in the PDF document] (I) wherein R<com:Sup>2< / com:Sup>, R<com:Sup>4< / com:Sup>, R<com:Sup>5< / com:Sup> and Y are as defined above. Suitable organometallic reagents include Gilman reagents formed by reaction of an alkyl lithium compound of formula (XXI): [Image disponible dans le document PDF, Image available in the PDF document] (XXI) wherein R<com:Sup>1< / com:Sup> is as defined for general formula (Xa) or (X); and a copper (I) salt, particularly a copper (I) halide such as copper (I) iodide. The reaction may be conducted in an organic solvent such as tetrahydrofuran, other ethers such as diethylether or a mixture thereof. Alternatively, the addition can be carried out using Grignard reagents R<com:Sup>1< / com:Sup>MgX, where R<com:Sup>1< / com:Sup> is as defined for general formula (Xa) or (X), and X is a halide, for example ethylmagnesium bromide and the reaction is suitably conducted in the presence of a zinc (II) salt such as zinc chloride and a catalytic amount of a copper (I) or copper(II) salt or complex, for example copper (I) chloride, copper (II) chloride or a copper(I) or copper (II) acetylacetonate (acac) complex. The reaction may be carried out in an organic solvent, for example an ether such as THF, 2-methyl THF, methyl tert-butyl ether (TBME), diethyl ether. Surprisingly, the reaction temperature is not particularly significant and while in some cases the reaction may be carried out at reduced temperature, for example at about -25 to 0 °C, it has also been successfully conducted at higher temperatures of up to about 55 °C. The method is particularly suitable for the preparation of compounds of general formula (IVa) or compounds of general formula (IV) in which R<com:Sup>4< / com:Sup> is C(O)OR<com:Sup>10< / com:Sup> from compounds of general formula (la) or from compounds of general formula (l), respectively, where R4 is also C(O)OR<com:Sup>10< / com:Sup>, where R<com:Sup>10< / com:Sup> is as defined above but is especially H, C<com:Sub>1-6< / com:Sub> alkyl or benzyl. Compounds of general formula (IVa) or of general formula (IV) with other R<com:Sup>4< / com:Sup> groups may be prepared from the above compounds of general formula (IVa) or compounds of general formula (IV), respectively, by methods which are familiar to those of skill in the art, as described below. A representative method of forming a compound of formula (IVa) or a compound of general formula (IV) is described in Example 6, Example 10 and Example 52. In one embodiment, the compound of formula (IVa) is: [Image disponible dans le document PDF, Image available in the PDF document] (IVa) wherein R<com:Sup>1< / com:Sup> is as defined above for compounds of general formula (Xa); and Y, R<com:Sup>2< / com:Sup>, R<com:Sup>4< / com:Sup> and R<com:Sup>5< / com:Sup> are as defined above for compounds of general formula (Ia). In one embodiment, the compound of formula (IVa) is: [Image disponible dans le document PDF, Image available in the PDF document] (IVa) wherein R<com:Sup>1< / com:Sup> is as defined above for compounds of general formula (Xa); and Y, R<com:Sup>2< / com:Sup>, R<com:Sup>4< / com:Sup> and R<com:Sup>5< / com:Sup> are as defined above for compounds of general formula (Ia). In one embodiment, the compound of formula (IVa) is: [Image disponible dans le document PDF, Image available in the PDF document] (IVa) wherein R<com:Sup>1< / com:Sup> is as defined above for compounds of general formula (Xa) and Y, R<com:Sup>2< / com:Sup>, R<com:Sup>4< / com:Sup> and R<com:Sup>5< / com:Sup> are as defined above for compounds of general formula (Ia). In one embodiment, the compound of formula (IV) is: [Image disponible dans le document PDF, Image available in the PDF document] (IV) wherein R<com:Sup>1< / com:Sup> is as defined above for compounds of general formula (X); and Y, R<com:Sup>2< / com:Sup>, R<com:Sup>4< / com:Sup> and R<com:Sup>5< / com:Sup> are as defined above for compounds of general formula (I). In one embodiment, the compound of formula (IV) is: [Image disponible dans le document PDF, Image available in the PDF document] (IV) wherein R<com:Sup>1< / com:Sup> is as defined above for compounds of general formula (X); and Y, R<com:Sup>2< / com:Sup>, R<com:Sup>4< / com:Sup> and R<com:Sup>5< / com:Sup> are as defined above for compounds of general formula (I). In one embodiment, the compound of formula (IV) is: [Image disponible dans le document PDF, Image available in the PDF document] (IV) wherein R<com:Sup>1< / com:Sup> is as defined above for compounds of general formula (X) and Y, R<com:Sup>2< / com:Sup>, R<com:Sup>4< / com:Sup> and R<com:Sup>5< / com:Sup> are as defined above for compounds of general formula (I). Step (b) The conversion of the compound of general formula (IVa) or the compound of general formula (IV) to the compound of general formula (Va) or to the compound of general formula (V) may be carried out by hydrogenation, usually catalytic hydrogenation. Suitable catalysts for the catalytic hydrogenation include a palladium / carbon, palladium / calcium carbonate, palladium / aluminium oxide, platinum / palladium or Raney® nickel catalyst. The reaction may be carried out in an organic solvent, which may be an alcoholic solvent such as methanol, ethanol or isopropanol; ethyl acetate; pyridine; acetic acid; cyclopentyl methyl ether (CPME), acetonitrile (MeCN) or N,N-dimethylformamide (DMF). The organic solvent may optionally be mixed with a co-solvent such as acetone or water and / or a base such as triethylamine may also be added. The choice of catalyst and solvent affects the ratio of the required product of general formula (Va) or general formula (V): [Image disponible dans le document PDF, Image available in the PDF document] (Va) / (V) to its isomer of general formula (XXXa) or general formula (XXX): [Image disponible dans le document PDF, Image available in the PDF document] (XXXa) / (XXX) More suitably, a palladium / carbon or palladium / calcium carbonate catalyst is used. Typically, in the catalyst the palladium is present in an amount of 5-10% by weight with respect to the weight of the matrix (where the matrix is the carbon, calcium carbonate etc.). Particularly suitable solvents and catalysts used for the reaction included a mixture of DMF and MeCN with a palladium / calcium carbonate catalyst and DMF with a palladium / carbon catalyst. Hydrogenation of a compound of formula (IVa) or a compound of formula (IV) will also reduce any alkene bonds, if present, in the linker Y. A representative method of forming a compound of general formula (Va) or a compound of general formula (V) is described in Example 7, Example 11 and Example 53. Step (c) The oxidation reaction of a compound of general formula (Va) to a compound of general formula (VIa) or of a compound of general formula (V) to a compound of general formula (VI) may be carried out using any suitable method. One suitable method is a Dess-Martin periodinane (1,1,1-triacetoxy-1,1-dihydro-1,2-benziodoxol-3-(1H)-one) oxidation, which may be carried out in a chlorinated solvent such as chloroform or dichloromethane at a temperature of about 15 to 25 °C, suitably at room temperature. An alternative oxidation method is oxidation using a hypochlorite, for example sodium hypochlorite, under acidic conditions, for example provided by acetic acid. The reaction may be carried out in an aqueous solvent and at a temperature of 0 to 15 °C, more usually at about 0 to 10 °C. Other oxidation methods include a Jones reaction using sodium dichromate or, more usually, chromic trioxide in dilute sulfuric acid. This process is known to be reliable for the clean conversion of bile acid hydroxyl groups to the corresponding keto derivatives (Bortolini et al, J. Org. Chem., 2002, 67, 5802). Alternatively oxidation may be carried out using TEMPO ((2,2,6,6-tetramethyl-piperidin-1-yl)oxy) or a derivative thereof. A representative example of such a process is described in Example 8, Example 12 and Example 54. Step (d) The reduction of a compound of general formula (VIa) or a compound of general formula (VI) to form a compound of general formula (Xa) or a compound of formula (X), respectively, utilises a reducing agent which is typically a hydride, such as sodium borohydride which may be used in a solvent such as a mixture of tetrahydrofuran and water. Typically, this reaction is carried out under basic conditions, for example in the presence of a strong base such as sodium or potassium hydroxide and at a temperature of about 0 to 110°C, more usually 60 to 100 °C. A compound of general formula (Xa) or a compound of formula (X) in which R<com:Sup>4< / com:Sup> is C(O)OH may be produced by the reduction of a compound in which R4 is C(O)OH. The process further includes one or more optional steps of converting compounds of general formulae (Ia), (IVa), (Va), (VIa) and (Xa) to other compounds of general formulae (la), (lVa), (Va), (Vla) and (Xa), or one or more optional steps of converting compounds of general formulae (I), (IV), (V), (VI) and (X) to other compounds of general formulae (I), (IV), (V), (VI) and (X). The optional steps consist of reacting the side chains of the compounds of general formulae (Ia), (IVa), (Va), (VIa) and (Xa) or of the compounds of general formulae (I), (IV), (V), (VI) and (X) as described below to arrive at compounds with alternative Y and / or R<com:Sup>4< / com:Sup> moieties. It should be noted that embodiments described above with respect to different R groups apply equally to the process embodiments just described. Side chain conversions The various side chain Y-R<com:Sup>4< / com:Sup> groups of compounds of formulae (la), (lla), (lllxa), (lllya), (IIIxz), (IIIyz), and, (IVa)-(XIa) and of compounds of formulae (I), (II), (IIIx), (IIIy) and, (IV)- (XI) may be prepared using conversion steps which are well known to the skilled person e.g. by reactions involving a side chain carboxylic acid, ester, OH or protected OH group. Analogues of the compounds of formulae (Va), (Vla), (V), (VI) and (X) in which a saturated side chain Y¹-R⁴ is converted to an unsaturated side chain Y-R⁴ may also be prepared by these methods as described in more detail below. Figure 1 shows the conversion of a compound of general formula (IIa) or of general formula (II) in which the side chain is -CH<com:Sub>2< / com:Sub>OH to other compounds of general formula (IIa) or of general formula (II), respectively, with different side chains. Such reactions are equally applicable to compounds of general formulae (Ia), (I), (IIIxa), (IIIx), (IIIya), (IIIy), (IIIxz), (IIIyz), (IVa)-(XIa) and (IV)-(XI), wherein appropriate (i.e. where chemically sensible). As shown in Figure 1, a compound of general formula (IIa) or a compound of general formula (II) wherein Y-R<com:Sup>4< / com:Sup> is CH<com:Sub>2< / com:Sub>-OH may be prepared from a plant sterol such as stigmasterol. As shown in Figure 1, a compound of general formula (IIa) or a compound of general formula (II) with the -CH<com:Sub>2< / com:Sub>OH side chain can be converted to compounds of general formula (IIa) or of general formula (II) with side chains including –CH<com:Sub>2< / com:Sub>-9-borabicyclo(3.3.1) nonyl, -CH<com:Sub>2< / com:Sub>CH<com:Sub>2< / com:Sub>CH[B(alkyl)<com:Sub>2< / com:Sub>]<com:Sub>2< / com:Sub>, -CH<com:Sub>2< / com:Sub>CN, -CH<com:Sub>2< / com:Sub>CH<com:Sub>2< / com:Sub>CN, -CH<com:Sub>2< / com:Sub>Br, -CH<com:Sub>2< / com:Sub>CH[C(O)OEt]<com:Sub>2< / com:Sub>, -CH<com:Sub>2< / com:Sub>-C<com:Math><semantics>≡<annotation encoding="application / x-tex">\equiv< / annotation>< / semantics>< / com:Math>CH, - <com:Math><semantics>CH2−CH=CH2<annotation encoding="application / x-tex">CH_2-CH=CH_2< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>=CH2<annotation encoding="application / x-tex">=CH_2< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−C(O)H<annotation encoding="application / x-tex">-C(O)H< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−CH2NH2<annotation encoding="application / x-tex">-CH_2NH_2< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>CH2OTBDMS<annotation encoding="application / x-tex">CH_2OTBDMS< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>CH2N3<annotation encoding="application / x-tex">CH_2N_3< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>CH2OMs<annotation encoding="application / x-tex">CH_2OMs< / annotation>< / semantics>< / com:Math>, [Image disponible dans le document PDF, Image available in the PDF document] [Image disponible dans le document PDF, Image available in the PDF document] or where X is O or S alkyl may be C<com:Sub>1-6< / com:Sub> alkyl and Et is ethyl; and also carboxylic acid mimetic groups including <com:Math><semantics>−C(O)NHSO2R10<annotation encoding="application / x-tex">-C(O)NHSO_2R^{10}< / annotation>< / semantics>< / com:Math> and <com:Math><semantics>−NHC(O)NH−SO2R10<annotation encoding="application / x-tex">-NHC(O)NH-SO_2R^{10}< / annotation>< / semantics>< / com:Math>. Compounds of general formulae (Ia), (IIa), (IIIxa), (IIIxa), (IIIxz), (IIIyz) and (IVa)-(XIa) and compounds of general formula (I), (II), (IIIx), (IIIy) and (IV)-(XI) with a side chain Y-OH (wherein Y is <com:Math><semantics>Y2<annotation encoding="application / x-tex">Y^2< / annotation>< / semantics>< / com:Math>-CH<com:Sub>2< / com:Sub>, and <com:Math><semantics>Y2<annotation encoding="application / x-tex">Y^2< / annotation>< / semantics>< / com:Math> is as defined above for Y except it is shorter in length by at least one carbon) can be converted to compounds in which the side chain is <com:Math><semantics>−Y2−C(O)H<annotation encoding="application / x-tex">-Y^2-C(O)H< / annotation>< / semantics>< / com:Math> by oxidation, for example using oxalyl chloride suitably in the presence of dimethyl sulfoxide and a base such as triethylamine. Alternatively, the oxidation may be carried out using Dess-Martin periodinane as shown in Example 27. In compounds of general formulae (la), (lla), (llxa), (llya), (llxz), (llyz) and (lVa)-(Xla) and compounds of general formula (I), (II), (IIIx), (IIIy) and (IV)-(XI) in which the side chain is -Y<com:Sup>2< / com:Sup>-C(O)H, the side chain can be extended, for example using an olefination with a compound of general formula (XXII): [Image disponible dans le document PDF, Image available in the PDF document] (XXII) where Y<com:Sup>3< / com:Sup> is as defined for Y in general formula (Ia) and general formula (IIa) or Y in general formula (I) and general formula (II) except that it may have a shorter carbon chain such that the linker Y of general formula (la) and general formula (lla) or of general formula (l) and general formula (II) can be a moiety -Y<com:Sup>2< / com:Sup>-CH<com:Sub>2< / com:Sub>CH<com:Sub>2< / com:Sub>-Y<com:Sup>3< / com:Sup>-, wherein Y<com:Sup>2< / com:Sup> and Y<com:Sup>3< / com:Sup> are as defined for Y except that they are shorter in length, wherein R<com:Sup>27< / com:Sup> is suitably C<com:Sub>1-6< / com:Sub> alkyl or benzyl, to give a compound in which the side chain is Y<com:Sup>2< / com:Sup>-CH=CH-Y<com:Sup>3< / com:Sup>-C(O)OR<com:Sup>27< / com:Sup>. An olefination reaction using (EtO)<com:Sub>2< / com:Sub>P(O)CH<com:Sub>2< / com:Sub>Y<com:Sup>3< / com:Sup>C(O)OR<com:Sup>27< / com:Sup> may also be used. The olefination may be carried out at about 15 to 25 °C, suitably room temperature, in a solvent such as dichloromethane. These compounds can, in turn, be converted to compounds in which R<com:Sup>4< / com:Sup> is the carboxylic acid mimetic group C(O)NHSO<com:Sub>2< / com:Sub>R<com:Sup>10< / com:Sup>, wherein R<com:Sup>10< / com:Sup> is as defined above, by reaction with: [Image disponible dans le document PDF, Image available in the PDF document] wherein R<com:Sup>10< / com:Sup> is as defined above, in the presence of a coupling agent such as 1-ethyl-3(3- dimethylaminopropyl)carbodiimide (EDCI). Compounds of general formula formulae (Ia), (IIa), (IIIxa), (IIIxa), (IIIxz), (IIIyz) and (IVa)- (XIa) and compounds of general formula formulae (I), (II), (IIIx), (IIIy) and (IV)-(XI) in which the group at the R<com:Sup>4< / com:Sup> position is OH can be protected with a silyl protecting group. This may be achieved by reaction with (XXIII) as described below, typically in an organic solvent and in the presence of a base, for example imidazole, or triethylamine. Such a reaction is shown in Example 22. [Image disponible dans le document PDF, Image available in the PDF document] (XXIII) wherein, R<com:Sup>16< / com:Sup> is as defined above and X<com:Sup>1< / com:Sup> is a leaving group, for example a halide such as chloride or a sulfonate leaving group such as trifluoromethanesulfonate (triflate), methanesulfonate (mesylate) or toluene sulfate (tosylate). Compounds of general formulae (Ia), (IIa), (IIIxa), (IIIxa), (IIIxz), (IIIyz) and (IVa)-(XIa) and compounds of general formulae (I), (II), (IIIx), (IIIy) and (IV)-(XI) in which R4 is OH may also be converted to compounds in which R4 is a sulfonate, for example methane sulfonate or toluene sulfonate, by reaction with a sulfonyl halide such as methane sulfonyl chloride, in the presence of a catalyst such as 4-dimethylaminopyridine (DMAP). Such a reaction is shown in Example 13. Alternatively, they may be converted to compounds of general formulae (Ia), (IIa), (IIIxa), (IIIya), (IIIxz), (IIIyz) and (IVa)-(XIa) or to compounds of general formulae (I), (II), (IIIx), (IIIy) and, (IV)-(XI) in which R4 is halo, for example bromo, by reaction with a halogenating agent, e.g. a brominating agent such as carbon tetrabromide as illustrated in Example 30 or N-bromosuccinimide, as illustrated in Example 35. Such sulfonate or halide compounds can then be converted to compounds of general formulae (Ia), (IIa), (IIIxa), (IIIxa), (IIIxz), (IIIyz) and (IVa)-(XIa) or compounds of general formulae (I), (II), (IIIx), (IIIy) and (IV)-(XI) in which R4 is cyano by reaction with a cyanide salt, for example sodium or potassium cyanide (see Example 35). Alternatively, reaction with acetonitrile in the presence of a base such as n-butyllithium leads to a chain lengthening reaction so that, for example, a side chain -CH<com:Sub>2< / com:Sub>-O-methanesulfonyl or -CH<com:Sub>2< / com:Sub>- Br is converted to a side chain -CH<com:Sub>2< / com:Sub>CH<com:Sub>2< / com:Sub>-CN. Such a reaction is shown in Example 33. Compounds with a sulfonate side chain can also be converted to compounds in which R<com:Sup>4< / com:Sup> is nitro by reaction with nitromethane in the presence of a base such as sodium or potassium carbonate. Compounds of formulae (Ia), (IIa), (IIIxa), (IIIya), (IIIxz), (IIIyz) and (IVa)-(XIa) and compounds of general formulae (I), (II), (IIIx), (IIIy) and, (IV)-(XI) in which the side chain is <com:Math><semantics>Y2<annotation encoding="application / x-tex">Y^2< / annotation>< / semantics>< / com:Math>-C(O)OH or an ester thereof may be converted to compounds in which the side chain is Y<com:Sup>2< / com:Sup>-CH=CH<com:Sub>2< / com:Sub> by reaction with Phl(OAc)<com:Sub>2< / com:Sub> in the presence of copper (II) acetate using a process similar to Hunsdiecker reaction (see J. Org. Chem., 1986, 51, 404-407 and V.C. Edelsztein et al. Tetrahedron, 2009, 65, 3615-3623). Such compounds with side chain - <com:Math><semantics>Y2<annotation encoding="application / x-tex">Y^2< / annotation>< / semantics>< / com:Math>-CH=CH<com:Sub>2< / com:Sub> may in turn be oxidised using, for example, osmium tetroxide as described in J. Org. Chem., 1986, 51, 404-407 to give a compound in which the side chain is -Y<com:Sup>2< / com:Sup>- CH(OH)-CH<com:Sub>2< / com:Sub>-OH. Such compounds may be oxidised to compounds in which the side chain is Y<com:Sup>2< / com:Sup>-CH(OH)-C(O)H, which may then be protected as a 1,3-dioxane or 1,3- dioxolane by reaction with 1,3-propane diol or 1,2-ethandiol in the presence of an acid catalyst such as toluene sulfonic acid. Similar reactions can be used to prepare the equivalent cyclic dithioacetals, and cyclic aminals. Compounds of general formulae (Ia), (IIa), (IIIxa), (IIIxa), (IIIxz), (IIIyz) and (IVa)-(XIa) and compounds of general formulae (I), (II), (IIIx), (IIIy) and (IV)-(XI) with side chain -Y-CH=CH<com:Sub>2< / com:Sub> may also be prepared by reduction of a compound with side chain -Y-C≡CH, typically by hydrogenation over a palladium catalyst, suitably Lindlar catalyst, as shown in Figure 1. Compounds of formulae (Ia), (IIa), (IIIxa), (IIIya), (IIIxz), (IIIyz) and (IVa)-(XIa) and compounds of general formulae (I), (II), (IIIx), (IIIy) and (IV)-(XI) with side chain -Y-C≡CH may be prepared from compounds with side chain Y-X, where X is a halo group, particularly bromo, by reaction with an organometallic reagent, for example: Li-C≡CH. Compounds of general formulae (Ia), (IIa), (IIIxa), (IIIxa), (IIIxz), (IIIyz) and (IVa)-(XIa) and compounds of general formulae (I), (II), (IIIx), (IIIy) and (IV)-(XI) in which the side chain - Y-R<com:Sup>4< / com:Sup> is -CH<com:Sub>2< / com:Sub>-OH may also be converted to compounds in which the side chain is =CH<com:Sub>2< / com:Sub>. This can be achieved by an elimination reaction in which the compound having side chain -Y-R<com:Sup>4< / com:Sup> is -CH<com:Sub>2< / com:Sub>-OH is reacted with an acid such as phosphoric acid, sulphuric acid or toluene sulphonic acid as shown in Figure 1. A similar reaction can be used to convert a compound with side chain <com:Math><semantics>−Y2<annotation encoding="application / x-tex">-Y^2< / annotation>< / semantics>< / com:Math>-CH<com:Sub>2< / com:Sub>-OH to a compound with side chain <com:Math><semantics>−Y2<annotation encoding="application / x-tex">-Y^2< / annotation>< / semantics>< / com:Math>-C=CH<com:Sub>2< / com:Sub>. Alternatively, compounds in which the side chain is <com:Math><semantics>=CH2<annotation encoding="application / x-tex">=CH_2< / annotation>< / semantics>< / com:Math> can be prepared by oxidising <com:Math><semantics>−Y2−CH2−OH<annotation encoding="application / x-tex">-Y^2-CH_2-OH< / annotation>< / semantics>< / com:Math> to <com:Math><semantics>Y2<annotation encoding="application / x-tex">Y^2< / annotation>< / semantics>< / com:Math>-CH(O) and then converting this to an alkene using an olefination reaction. Compounds of general formulae (Ia), (IIa), (IIIxa), (IIIxa), (IIIxz), (IIIyz) and (IVa)-(XIa) or compounds of general formulae (I), (II), (IIIx), (IIIy) and (IV)-(XI) with side chain Y-C≡CH, =CH<com:Sub>2< / com:Sub> or -Y<com:Sup>2< / com:Sup>-C=CH<com:Sub>2< / com:Sub> may be reacted with a borane of formula: [Image disponible dans le document PDF, Image available in the PDF document] to give compounds in which the side chain is -Y-CH<com:Sub>2< / com:Sub>-C(BR<com:Sup>10< / com:Sup>R<com:Sup>11< / com:Sup>)<com:Sub>2< / com:Sub>, -CH<com:Sub>2< / com:Sub>-BR<com:Sup>10< / com:Sup>R<com:Sup>11< / com:Sup> or -Y<com:Sup>2< / com:Sup>- CH<com:Sub>2< / com:Sub>-BR<com:Sup>10< / com:Sup>R<com:Sup>11< / com:Sup> respectively. An example of this reaction is shown in Figure 1. Compounds of formulae (Ia), (IIa), (IIIxa), (IIIxa), (IIIxz), (IIIyz) and (IVa)-(XIa) and compounds of general formulae (I), (II), (IIIx), (IIIy) and (IV)-(XI) in which the side chain is -CH<com:Sub>2< / com:Sub>-BR<com:Sup>10< / com:Sup>R<com:Sup>11< / com:Sup> or -Y<com:Sup>2< / com:Sup>-CH<com:Sub>2< / com:Sub>-BR<com:Sup>10< / com:Sup>R<com:Sup>11< / com:Sup> may be reacted with, for example phenoxyacetic acid to give a corresponding compound in which the side chain is -CH<com:Sub>2< / com:Sub>-C(O)OH or -Y<com:Sup>2< / com:Sup>-CH<com:Sub>2< / com:Sub>- C(O)OH. Compounds of general formulae (Ia), (IIa), (IIIxa), (IIIxa), (IIIxz), (IIIyz) and (IVa)-(XIa) and compounds of general formulae (I), (II), (IIIx), (IIIy) and (IV)-(XI) in which R4 is - CH[C(O)OR<com:Sup>10< / com:Sup>]<com:Sub>2< / com:Sub> may be prepared from compounds in which R<com:Sup>4< / com:Sup> is halo, for example bromo, by reaction with a malonate ester in the presence of a base such as sodium hydride, as shown in Figure 1. A reaction of this type is illustrated in Example 32. Compounds of general formulae (Ia), (IIa), (IIIxa), (IIIxa), (IIIxz), (IIIyz) and (IVa)-(XIa) and compounds of general formulae (I), (II), (IIIx), (IIIy) and (IV)-(XI) in which R⁴ is a malonate ester -CH[C(O)OR<com:Sup>10< / com:Sup>]<com:Sub>2< / com:Sub> may be heated under acidic or basic conditions to give compounds in which R<com:Sup>4< / com:Sup> is CH<com:Sub>2< / com:Sub>C(O)OH. Compounds of general (Ia), (IIa), (IIIxa), (IIIxa), (IIIxz), (IIIyz) and (IVa)-(XIa) and compounds of general formulae (I), (II), (IIIx), (IIIy) and (IV)-(XI) in which the side chain is -Y-C(O)OH may also be converted to compounds in which the side chain is -Y-C(O)-CH<com:Sub>2< / com:Sub>- N<com:Sub>2< / com:Sub> by reaction with phosgene to form the acid chloride, followed by reaction with diazomethane. The diazomethane may be formed in situ using conventional methods, e.g. the treatment of N-nitroso-N-methylurea with aqueous sodium or potassium hydroxide in diethyl ether. Suitably the diazomethane is used in excess, typically in an amount of greater than 2 equivalents compared with the acid chloride. The reaction is typically conducted in an organic solvent such as diethyl ether, toluene or a mixture thereof. The reaction is carried out at a temperature of about -5 to 15 °C, typically 0-10 °C. The compound with side chain <com:Math><semantics>−Y−C(O)−CH2−N2<annotation encoding="application / x-tex">-Y-C(O)-CH_2-N_2< / annotation>< / semantics>< / com:Math> may be treated with an aqueous silver compound, for example silver nitrate, at an elevated temperature and in the presence of an alcohol of formula: [Image disponible dans le document PDF, Image available in the PDF document] wherein R<com:Sup>10a< / com:Sup> is as defined for R<com:Sup>10< / com:Sup> in general formula (la) or in general formula (l) except that it is not H. Most suitably, <com:Math><semantics>R10a<annotation encoding="application / x-tex">R^{10a}< / annotation>< / semantics>< / com:Math> is <com:Math><semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics>< / com:Math> alkyl or benzyl. Under these conditions, the compound undergoes a Wolff rearrangement to give a compound in which the side chain is -Y-CH<com:Sub>2< / com:Sub>-C(O)OR<com:Sup>10a< / com:Sup> and thus this sequence can be used to lengthen the side chain. Compounds of general formulae (Ia), (IIa), (IIIxa), (IIIya), (IIIxz), (IIIyz) and (IVa)-(XIa) or compounds of general formulae (I), (II), (IIIx), (IIIy) and (IV)-(XI) in which the side chain is Y-C(O)OH may be converted to compounds in which the side chain is -Y<com:Sup>2< / com:Sup>-CH<com:Sub>2< / com:Sub>-CN by reaction with sodium nitrite under acidic conditions, for example in the presence of trifluoroacetic acid and trifluroroacetic anhydride (C. D. Schteingart and A. T. Hofmann, Journal of Lipid Research, 1988, 29, 1387-1395; Valentina Sepe et al, Eur. J. Org. Chem. 2012, 5187–5194). Compounds of general formulae (Ia), (IIa), (IIIxa), (IIIxa), (IIIxz), (IIIyz) and (IVa)-(XIa) or compounds of general formulae (I), (II), (IIIx), (IIIy) and (IV)-(XI) in which the side chain is Y<com:Sup>2< / com:Sup>-C(O)H (where Y<com:Sup>2< / com:Sup> is as defined above for Y except that it is shorter in length by one carbon) may be converted to compounds in which the side chain is -Y-CH(XR<com:Sup>10< / com:Sup>)(XR<com:Sup>11< / com:Sup>), where Y is <com:Math><semantics>−Y2<annotation encoding="application / x-tex">-Y^2< / annotation>< / semantics>< / com:Math>-CH<com:Sub>2< / com:Sub>-, for example <com:Math><semantics>−Y2<annotation encoding="application / x-tex">-Y^2< / annotation>< / semantics>< / com:Math> -CH(OR<com:Sup>10< / com:Sup>)(OR<com:Sup>11< / com:Sup>) or <com:Math><semantics>−Y2<annotation encoding="application / x-tex">-Y^2< / annotation>< / semantics>< / com:Math> -CH(SR<com:Sup>10< / com:Sup>)(SR<com:Sup>11< / com:Sup>) where R<com:Sup>10< / com:Sup> and R<com:Sup>11< / com:Sup> together with the atoms to which they are attached join to form a cyclic group. This can be achieved by reacting the compound in which the side chain is <com:Math><semantics>Y2<annotation encoding="application / x-tex">Y^2< / annotation>< / semantics>< / com:Math>-C(O)H with a compound of formula: [Image disponible dans le document PDF, Image available in the PDF document] where X<com:Sup>3< / com:Sup> is O, S or NH and p is 1 to 4 but usually is 2 or 3, or with a protected version of such a compound, for example in which OH or SH groups are protected with trimethylsilyl as shown in Example 28. Compounds of general formulae (Ia), (IIa), (IIIxa), (IIIxa), (IIIxz), (IIIyz) and (IVa)-(XIa) or compounds of general formulae (I), (II), (IIIx), (IIIy) and (IV)-(XI) in which the side chain is <com:Math><semantics>Y2<annotation encoding="application / x-tex">Y^2< / annotation>< / semantics>< / com:Math>-C(O)H may also be converted to compounds with side chain -<com:Math><semantics>Y2<annotation encoding="application / x-tex">Y^2< / annotation>< / semantics>< / com:Math>-CH(OH)-CH<com:Sub>2< / com:Sub>- <com:Math><semantics>CH(OR10)(OR11)<annotation encoding="application / x-tex">CH(OR^{10})(OR^{11})< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−Y2−CH(OH)−CH2−CH(R10)(OR11)<annotation encoding="application / x-tex">-Y^2-CH(OH)-CH_2-CH(R^{10})(OR^{11})< / annotation>< / semantics>< / com:Math> or <com:Math><semantics>−Y2−CH(OH)−CH2−CH(SR10)(SR11)<annotation encoding="application / x-tex">-Y^2-CH(OH)-CH_2-CH(SR^{10})(SR^{11})< / annotation>< / semantics>< / com:Math> by reaction with an appropriate organometallic reagent, typically a Grignard reagent of formula: XMg-CH<com:Sub>2< / com:Sub>-R<com:Sup>4c< / com:Sup>; where X is halo, typically bromo, and R<com:Sup>4c< / com:Sup> -CH(OR<com:Sup>10< / com:Sup>)(OR<com:Sup>11< / com:Sup>), -CH(R<com:Sup>10< / com:Sup>)(OR<com:Sup>11< / com:Sup>) or CH(SR<com:Sup>10< / com:Sup>)(SR<com:Sup>11< / com:Sup>). Compounds of general formulae (Ia), (IIa), (IIIxa), (IIIxa), (IIIxz), (IIIyz) and (IVa)-(XIa) or compounds of general formulae (I), (II), (IIIx), (IIIy) and (IV)-(XI) in which the side chain is -Y<com:Sup>2< / com:Sup>-CH(OH)-CH<com:Sub>2< / com:Sub>-CH(OR<com:Sup>10< / com:Sup>)(OR<com:Sup>11< / com:Sup>) can be converted to compounds in which the side chain is -Y<com:Sup>2< / com:Sup>-CH=CH-C(O)H by reaction with an acid. Following this, the aldehyde can be oxidised to give a carboxylic acid and / or the alkylenene bond can be reduced by hydrogenation to give a saturated side chain in which Y is -Y<com:Sup>2< / com:Sup>-CH<com:Sub>2< / com:Sub>CH<com:Sub>2< / com:Sub>-. Compounds of general formulae (Ia), (IIa), (IIIxa), (IIIya), (IIIxz), (IIIyz) and (IVa)-(XIa) or compounds of general formulae (I), (II), (IIIx), (IIIy) and (IV)-(XI) in which R<com:Sup>4< / com:Sup> is -N<com:Sub>3< / com:Sub> may be prepared from compounds of (la), (lla), (lllxa), (lllya) and (lVa)-(Xla) or compounds of general formulae (I), (II), (IIIx), (IIIy) and (IV)-(XI), respectively, in which R4 is a leaving group such as toluene sulfonate, methane sulfonate or compounds of general formulae (la), (lla), (lllxa), (lllya), (lllxz), (lllyz) and (lVa)-(Xla) or compounds of general formulae (I), (II), (IIIx), (IIIy) and (IV)-(XI) in which R⁴ is halo (for example bromo) or a sulfonyl leaving group such as toluene sulfonate or methane sulfonate, by reaction with sodium azide. This is illustrated in Example 34. Compounds of general formulae (Ia), (IIa), (IIIxa), (IIIya), (IIIxz), (IIIyz) and (IVa)-(XIa) or compounds of general formulae (I), (II), (IIIx), (IIIy), (IIIxz), (IIIyz) and (IV)-(XI) in which R4 is NH<com:Sub>2< / com:Sub> may be obtained by reduction of compounds of general formulae (la), (lla), (llxa), (IIIya) and (IVa)-(XIa) or compounds of general formulae (I), (II), (IIIx), (IIIy) and (IV)-(XI), respectively, in which R<com:Sup>4< / com:Sup> is azide as illustrated in Example 34. Compounds of general formulae (Ia), (IIa), (IIIxa), (IIIya), (IIIxz), (IIIyz) and (IVa)-(XIa) or compounds of general formulae (I), (II), (IIIx), (IIIy) and (IV)-(XI) in which R4 is - NHC(O)NHSO<com:Sub>2< / com:Sub>R<com:Sup>10< / com:Sup> may be prepared from compounds in which R<com:Sup>4< / com:Sup> is NH<com:Sub>2< / com:Sub> using a coupling reaction with a compound of formula: [Image disponible dans le document PDF, Image available in the PDF document] wherein R<com:Sup>10< / com:Sup> is as defined above; in the presence of a reagent such as N,N'-carbonyldiimidazole (CDI). Compounds of general formulae (Ia), (IIa), (IIIxa), (IIIxa), (IIIxz), (IIIyz) and (IVa)-(XIa) or compounds of general formulae (I), (II), (IIIx), (IIIy) and (IV)-(XI) in which R4 is tetrazole-5- yl may be prepared from compounds of general formulae (la), (lla), (llxa), (lllxa), (lllxz), (IIIyz) and (IV)-(XI) or compounds of general formulae (I), (II), (IIIx), (IIIy) and (IV)-(XI), respectively, in which R<com:Sup>4< / com:Sup> is CN by reaction with azidotrimethylsilane / dibutylstannanone or Bu<com:Sub>3< / com:Sub>SnN<com:Sub>3< / com:Sub> as described in US2016 / 0145295. Alternatively, the compound in which R⁴ is CN may be reacted with sodium azide in the presence of an acid. For example, NaN<com:Sub>3< / com:Sub> / NH<com:Sub>4< / com:Sub>Cl in toluene / DMF (Organic and Biomolecular Chemistry, 2008, 6, 4108) or NaN<com:Sub>3< / com:Sub> / NEt<com:Sub>3< / com:Sub>.HCl in DMF (Brown et al.; Bioorg Med Chem Lett, 2002, 12, 3171). Alternatively, a compound in which R4 is azide may be reacted with a suitable cyanide compound, for example tosyl cyanide, under reducing conditions to give a compound in which R<com:Sup>4< / com:Sup> is tetrazol-1-yl. Compounds of general formulae (Ia), (IIa), (IIIxa), (IIIxa), (IIIxz), (IIIyz) and (IVa)-(XIa) or compounds of general formulae (I), (II), (IIIx), (IIIy) and (IV)-(XI) in which R4 is amino tetrazole can be prepared from a compound in which the group at the R4 position is mesyl by reaction with 5-amino tetrazole. Compounds of general (la), (lla), (llixa), (llixa), (llixz), (llixz) and (lVa)-(Xla) or compounds of general formulae (I), (II), (IIIx), (IIIy) and (IV)-(XI) in which the side chain is -Y<com:Sup>2< / com:Sup>-C(O)H may also be converted to compounds -Y<com:Sup>2< / com:Sup>-CH<com:Sub>2< / com:Sub>-NR<com:Sup>10< / com:Sup>R<com:Sup>11< / com:Sup> by reductive amination, using a reducing agent such as a hydride, borohydride or cyanoborohydride (for example sodium borohydride or sodium cyanoborohydride) and an amine of formula: [Image disponible dans le document PDF, Image available in the PDF document] where R<com:Sup>10< / com:Sup> and R<com:Sup>11< / com:Sup> are as defined above. Compounds of general formulae (Ia), (IIa), (IIIxa), (IIIxa), (IIIxz), (IIIyz) and (IVa)-(XIa) or compounds of general formulae (I), (II), (IIIx), (IIIy) and (IV)-(XI) in which R<com:Sup>4< / com:Sup> is C(O)OR<com:Sup>10< / com:Sup> may be converted to a compound of the same general formula, in which R<com:Sup>4< / com:Sup> is OC(O)R<com:Sup>10< / com:Sup>, C(O)NR<com:Sup>10< / com:Sup>R<com:Sup>11< / com:Sup>, OR<com:Sup>10< / com:Sup>, OSi(R<com:Sup>13< / com:Sup>)<com:Sub>3< / com:Sub>, S(O)R<com:Sup>10< / com:Sup>, SO<com:Sub>2< / com:Sub>R<com:Sup>10< / com:Sup>, OSO<com:Sub>2< / com:Sub>R<com:Sup>10< / com:Sup>, SO<com:Sub>3< / com:Sub>R<com:Sup>10< / com:Sup>, OSO<com:Sub>3< / com:Sub>R<com:Sup>10< / com:Sup>, halo, CN, <com:Math><semantics>C(O)R10<annotation encoding="application / x-tex">C(O)R^{10}< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>CH(OR10)(OR11),CH(R10)(OR11),CH(SR10)(SR11),NR10R11,<annotation encoding="application / x-tex">CH(OR^{10})(OR^{11}), CH(R^{10})(OR^{11}), CH(SR^{10})(SR^{11}), NR^{10}R^{11},< / annotation>< / semantics>< / com:Math> BR<com:Sup>10< / com:Sup>R<com:Sup>11< / com:Sup>. <com:Math><semantics>C(O)CH2N2<annotation encoding="application / x-tex">C(O)CH_2N_2< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−CH=CH2<annotation encoding="application / x-tex">-CH=CH_2< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−C≡CH<annotation encoding="application / x-tex">-C\equiv CH< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>CH[C(O)OR10]2<annotation encoding="application / x-tex">CH[C(O)OR^{10}]_2< / annotation>< / semantics>< / com:Math> or <com:Math><semantics>CH(BR10R11)2<annotation encoding="application / x-tex">CH(BR^{10}R^{11})_2< / annotation>< / semantics>< / com:Math>, azide or a carboxylic acid mimetic group such as tetrazole. Compounds of general formulae (Ia), (IIa), (IIIxa), (IIIxa), (IIIxz), (IIIyz) and (IVa)-(XIa) or compounds of general formulae (I), (II), (IIIx), (IIIy) and (IV)-(XI) in which R⁴ is SO₃R¹⁰ may be synthesised from compounds in which R4 is C(O)OH by the methods taught in WO2008 / 002573, WO2010 / 014836 and WO2014 / 066819. Thus a compound of general formulae (la), (lla), (lllxa), (lllya), (lllxz), (lllyz) and (lVa)- (XIa) or a compound of general formulae (I), (II), (IIIx), (IIIy) and (IV)-(XI) in which R4 is C(O)OH may first be reacted with a <com:Math><semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics>< / com:Math> alkanoyl or benzoyl chloride or with a <com:Math><semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics>< / com:Math> alkanoic anhydride to protect any OH groups. The protected compound may then be reacted with a reducing agent such as a hydride, suitably lithium aluminium hydride or sodium borohydride in order to reduce the carboxylic acid group to OH. The alcohol group may be replaced by a halogen, for example bromine or iodine, using the triphenyl phosphine / imidazole / halogen method described by Classon et al., J. Org. Chem., 1988, 53, 6126-6130. The halogenated compound may then be reacted with sodium sulphite in an alcoholic solvent to give a compound with a SO<com:Sub>3< / com:Sub><com:Sup>-< / com:Sup> Na<com:Sup>+< / com:Sup> substituent. A compound of general formulae (Ia), (IIa), (IIIxa), (IIIxa), (IIIxz), (IIIyz) and (IVa)-(XIa) or a compound of general formulae (I), (II), (IIIx), (IIIy) and (IV)-(XI) in which R<com:Sup>4< / com:Sup> is OSO<com:Sub>3< / com:Sub>R<com:Sup>10< / com:Sup> can be obtained by reacting the alcohol obtained from reducing the protected carboxylic acid as described above with chlorosulfonic acid in the presence of a base such as triethylamine to yield the protected triethylamine salt. Protecting groups can be removed using base hydrolysis as described above. Reduction of the carboxylic acid followed by reaction of the resultant alcohol with a sulfonyl chloride yields a compound of general formulae (Ia), (IIa), (IIIxa), (IIIxa), (IIIxz), (IIIyz) and (IVa)-(XIa) or a compound of general formulae (I), (II), (IIIx), (IIIy) and (IV)-(XI) in which R<com:Sup>4< / com:Sup> is OSO<com:Sub>2< / com:Sub>R<com:Sup>10< / com:Sup>. Compounds of general formulae (Ia), (IIa), (IIIxa), (IIIya), (IIIxz), (IIIyz) and (IVa)-(XIa) or compounds of general formulae (I), (II), (IIIx), (IIIy) and (IV)-(XI) in which R4 is C(O)NR10R11 may be prepared from the carboxylic acid by reaction with an amine of formula H-NR<com:Sup>10< / com:Sup>R<com:Sup>11< / com:Sup> in a suitable solvent with heating. Compounds of general formulae (la), (lla), (llxa), (llya) and (IVa)-(XIa) or compounds of general formulae (I), (II), (IIIx), (IIIy), (IIIxz), (IIIyz) and (IV)-(XI) in which R<com:Sup>4< / com:Sup> is C(O)NR<com:Sup>10< / com:Sup>R<com:Sup>11< / com:Sup> or OSO<com:Sub>3< / com:Sub>R<com:Sup>10< / com:Sup> may also be prepared by methods similar to those described by Festa et al., J. Med. Chem., 2014, 57, 8477–8495. An example of this is the synthesis of compounds of general formulae (la), (lla), (llxa), (IIIya), (IIIxz), (IIIyz) and (IVa)-(XIa) or compounds of general formulae (I), (II), (IIIx), (IIIy) and (IV)-(XI) in which R<com:Sup>4< / com:Sup> is C(O)NH(CH<com:Sub>2< / com:Sub>)<com:Sub>2< / com:Sub>SO<com:Sub>3< / com:Sub>H or C(O)NHCH<com:Sub>2< / com:Sub>CO<com:Sub>2< / com:Sub>H or salts thereof from compounds of the same general formula in which R4 is C(O)OH by reaction with taurine or glycine respectively in the presence of a coupling reagent such as iso-butylchloroformate and a base such as triethylamine. A compound of general formulae (Ia), (IIa), (IIIxa), (IIIxa), (IIIxz), (IIIyz) and (IVa)-(XIa) or a compound of general formulae (I), (II), (IIIx), (IIIy) and (IV)-(XI) in which R<com:Sup>4< / com:Sup> is C(O)R<com:Sup>10< / com:Sup> can be obtained by reduction of a compound in which R<com:Sup>4< / com:Sup> is C(O)OR<com:Sup>10< / com:Sup> using one equivalent of diisobutyl aluminium hydride (DIBAL-H) to obtain an aldehyde in which R4 is C(O)H (see, for example, WO2011 / 014661). Alternatively, the aldehyde may be prepared by oxidation of a protected compound in which R⁴ is OH prepared as described above. The oxidation may be Swern oxidation carried out using oxalyl chloride and dimethyl sulfoxide followed by triethylamine (see, for example Xiang-Dong Zhou et al, Tetrahedron, 2002, 58, 10293-10299). Alternatively, the oxidation may be carried out using an oxidising agent such as pyridinium chlorochromate (PCC) as described by Carnell et al (J. Med. Chem., 2007, 50, 2700-2707. A compound of general formulae (Ia), (IIa), (IIIxa), (IIIya), (IIIxz), (IIIyz) and (IVa)-(XIa) or a compound of general formulae (I), (II), (IIIx), (IIIy) and (IV)-(XI) in which R<com:Sup>4< / com:Sup> is C(O)R<com:Sup>10< / com:Sup> where R<com:Sup>10< / com:Sup> is other than hydrogen can be obtained by known methods, for example by the reaction of the aldehyde in which R<com:Sup>4< / com:Sup> is C(O)H with a suitable Grignard reagent, followed by oxidation. Such methods are well known to those of skill in the art. Compounds of general formulae (Ia), (IIa), (IIIxa), (IIIxa), (IIIxz), (IIIyz) and (IVa)-(XIa) or compounds of general formulae (I), (II), (IIIx), (IIIy) and (IV)-(XI) with other R4 groups may be prepared from the above compounds of the same general formula, by methods which are familiar to those of skill in the art. General information The invention will now be described in greater detail with reference to the examples. In the examples, the following abbreviations were used: [Image disponible dans le document PDF, Image available in the PDF document] [Image disponible dans le document PDF, Image available in the PDF document] [Image disponible dans le document PDF, Image available in the PDF document] EXAMPLES GENERAL PROCEDURES Examples 1 and 2 – Epoxidation reactions Example 1 – Synthesis of <com:Math><semantics>(6β,7β,22E)<annotation encoding="application / x-tex">(6\beta, 7\beta, 22E)< / annotation>< / semantics>< / com:Math>-6,7-epoxy-3-oxo-4,22-choladien-24-oic acid ethyl ester (IA) using TCCA in acetone / H<com:Sub>2< / com:Sub>O [Image disponible dans le document PDF, Image available in the PDF document] (IA) Synthesis of <com:Math><semantics>(6β,7α,22E)<annotation encoding="application / x-tex">(6\beta, 7\alpha, 22E)< / annotation>< / semantics>< / com:Math>-7-chloro-6-hydroxy-3-oxo-4,22-choladien-24-oic acid ethyl ester (IIIxA) or (6α, 7β, 22E)-6-chloro-7-hydroxy-3-oxo-4,22-choladien-24-oic acid ethyl ester) (IIIyA) [Image disponible dans le document PDF, Image available in the PDF document] [Image disponible dans le document PDF, Image available in the PDF document] [Image disponible dans le document PDF, Image available in the PDF document] (IIA) (IIIxA) (IIIyA) (22E)-3-oxo-4,6,22-cholatrien-24-oic acid ethyl ester (2.0 g, 5.0 mmol, obtained from Stigmasterol as described in Example 1 of patent application No. PCT / GB2015 / 053516; WO2016 / 079517A1) was dissolved in acetone:H<com:Sub>2< / com:Sub>O (12:1, 15 vol). TCCA (0.47 g, 0.4 eq) was added as a single portion and the solution stirred for 1.5 h. The resultant mixture was filtered, diluted with CH<com:Sub>2< / com:Sub>Cl<com:Sub>2< / com:Sub> and washed with 10% NaHSO<com:Sub>3< / com:Sub> aq. (25 mL) followed by H<com:Sub>2< / com:Sub>O (25 mL). The organic layer was dried over Na<com:Sub>2< / com:Sub>SO<com:Sub>4< / com:Sub>, filtered and concentrated to give (6β, 7α, 22E)-7-chloro-6-hydroxy-3-oxo-4,22-choladien-24-oic acid ethyl ester (IIIxA) or (6α, 7β, 22E)-7-hydroxy-6-chloro-3-oxo-4,22-choladien-24-oic acid ethyl ester (IIIyA) (0.89 g, 2.0 mmol) after column chromatography as an oily solid. <com:Sup>1< / com:Sup>H NMR (400 MHz, CDCl<com:Sub>3< / com:Sub>): <com:Math><semantics>δ<annotation encoding="application / x-tex">\delta< / annotation>< / semantics>< / com:Math> = 6.8 (1H, dd, <com:Math><semantics>J<annotation encoding="application / x-tex">J< / annotation>< / semantics>< / com:Math> = 15.6, 9.0, C22H), 5.88 (1H, s, C4H), 5.74 (1H, d, <com:Math><semantics>J=15.6<annotation encoding="application / x-tex">J = 15.6< / annotation>< / semantics>< / com:Math>, C23H), 4.35 (1H, d, <com:Math><semantics>J=3.0<annotation encoding="application / x-tex">J = 3.0< / annotation>< / semantics>< / com:Math>, C6H), 4.19-4.14 (3H, m, OC<com:Math><semantics>H2<annotation encoding="application / x-tex">H_2< / annotation>< / semantics>< / com:Math>CH<com:Sub>3< / com:Sub> + C7H), 2.54-1.08 (27H, m), 0.79 (3H, s, CH<com:Sub>3< / com:Sub>). <com:Sup>13< / com:Sup>C NMR (100 MHz, CDCl<com:Sub>3< / com:Sub>): <com:Math><semantics>δ<annotation encoding="application / x-tex">\delta< / annotation>< / semantics>< / com:Math> = 199.9, 197.1, 164.7, 154.3, 129.4, 119.2, 77.1, 63.9, 60.2, 54.8, 50.9, 44.5, 42.7, 39.6, 38.9, 37.8, 36.8, 34.2, 34.0, 27.9, 23.1, 20.6, 20.3, 19.2, 14.3, 12.3. HRMS (ESI-TOF) <com:Math><semantics>m / z<annotation encoding="application / x-tex">m / z< / annotation>< / semantics>< / com:Math>: (M+H)<com:Sup>+< / com:Sup> calcd for C<com:Sub>26< / com:Sub>H<com:Sub>38< / com:Sub>Cl<com:Sub>1< / com:Sub>O<com:Sub>4< / com:Sub> 449.2453; found: 449.2425; Synthesis of (6β, 7β, 22E)-6,7-epoxy-3-oxo-4,22-choladien-24-oic acid ethyl ester (IA) [Image disponible dans le document PDF, Image available in the PDF document] [Image disponible dans le document PDF, Image available in the PDF document] (6<com:Math><semantics>β<annotation encoding="application / x-tex">\beta< / annotation>< / semantics>< / com:Math>, 7<com:Math><semantics>α<annotation encoding="application / x-tex">\alpha< / annotation>< / semantics>< / com:Math>, 22E)-7-chloro-6-hydroxy-3-oxo-4,22-choladien-24-oic acid ethyl ester (IIIxa) or (6α, 7β, 22E)-7-hydroxy-6-chloro-3-oxo-4,22-choladien-24-oic acid ethyl ester (IIIya) (0.89) g, 2.0 mmol) was dissolved in CH<com:Sub>2< / com:Sub>Cl<com:Sub>2< / com:Sub> (10 mL) and DBU (0.45 mL, 1.5 eq) was added. The solution was stirred for 18 h and then additional DBU (0.15 mL, 0.5 eq) added. After stirring for a further 4.5 h DBU (0.15 mL, 0.5 eq) was added and the solution stirred for 19 h. The solution was concentrated to dryness giving the title compound (0.40 g, 1.0 mmol) after column chromatography as an off white solid. <com:Sup>1< / com:Sup>H NMR (400 MHz, CDCl<com:Sub>3< / com:Sub>): <com:Math><semantics>δ<annotation encoding="application / x-tex">\delta< / annotation>< / semantics>< / com:Math> = 6.8 (1H, dd, <com:Math><semantics>J<annotation encoding="application / x-tex">J< / annotation>< / semantics>< / com:Math> = 15.6, 9.0, C22H), 6.13 (1H, s, C4H), 5.74 (1H, d, <com:Math><semantics>J=15.6<annotation encoding="application / x-tex">J = 15.6< / annotation>< / semantics>< / com:Math>, C23H), 4.17 (2H, q, <com:Math><semantics>J=7.1<annotation encoding="application / x-tex">J = 7.1< / annotation>< / semantics>< / com:Math>, OC<com:Math><semantics>H2<annotation encoding="application / x-tex">H_2< / annotation>< / semantics>< / com:Math>CH<com:Sub>3< / com:Sub>), 3.35-3.33 (2H, m, C6H and C7H), 2.63-2.53 (1H, m), 2.43-2.24 (2H, m), 2.02-1.03 (23H, m), 0.76 (3H, s, CH<com:Sub>3< / com:Sub>). <com:Sup>13< / com:Sup>C NMR (100 MHz, CDCl<com:Sub>3< / com:Sub>): <com:Math><semantics>δ<annotation encoding="application / x-tex">\delta< / annotation>< / semantics>< / com:Math> = 198.2, 166.9, 163.0, 154.0, 129.3, 119.4, 60.2, 59.1, 55.7, 54.7, 52.6, 51.6, 43.7, 39.6, 39.2, 36.6, 36.1, 35.5, 34.1, 28.0, 23.8, 21.3, 19.2, 16.8, 14.3, 12.1. HRMS (ESI-TOF) <com:Math><semantics>m / z<annotation encoding="application / x-tex">m / z< / annotation>< / semantics>< / com:Math>: (M+H)<com:Sup>+< / com:Sup> calcd for C<com:Sub>26< / com:Sub>H<com:Sub>37< / com:Sub>O<com:Sub>4< / com:Sub> 413.2686; found: 413.2691. Example 2 – Synthesis of <com:Math><semantics>(6β,7β,22E)<annotation encoding="application / x-tex">(6\beta, 7\beta, 22E)< / annotation>< / semantics>< / com:Math>-6,7-epoxy-3-oxo-4,22-choladien-24-oic acid ethyl ester using TCCA in acetic acid [Image disponible dans le document PDF, Image available in the PDF document] (IA) Synthesis of (6<com:Math><semantics>β<annotation encoding="application / x-tex">\beta< / annotation>< / semantics>< / com:Math>, 7<com:Math><semantics>α<annotation encoding="application / x-tex">\alpha< / annotation>< / semantics>< / com:Math>, 22E)-6-acetoxy-7-chloro -3-oxo-4,22-choladien-24-oic acid ethyl ester [Image disponible dans le document PDF, Image available in the PDF document] (22E)-3-oxo-4,6,22-cholatrien-24-oic acid ethyl ester (1.0 g, 2.5 mmol) was dissolved in AcOH (10 mL). TCCA (235 mg) was added as a single portion and the solution stirred for 18h. The mixture was diluted with EtOAc (100 mL) and washed with 5% aq. NaHSO<com:Sub>3< / com:Sub> (100 mL) followed by H<com:Sub>2< / com:Sub>O (2×50 mL) and 5% aq. NaHCO<com:Sub>3< / com:Sub> (50 mL). The organic layer was dried over Na<com:Sub>2< / com:Sub>SO<com:Sub>4< / com:Sub>, filtered and concentrated in vacuo. (6β, 7α, 22E)-6-acetoxy-7-chloro-3-oxo- 4,22-choladien-24-oic acid ethyl ester (454 mg, yellow oil) was isolated by column chromatography (SiO<com:Sub>2< / com:Sub>, eluting with Heptane : EtOAc gradient). <com:Sup>1< / com:Sup>H NMR (400 MHz, CDCl<com:Sub>3< / com:Sub>): <com:Math><semantics>δ<annotation encoding="application / x-tex">\delta< / annotation>< / semantics>< / com:Math> = 6.81 (1H, dd, J 15.6, 9.0, C22H), 6.02 (1H, s, C4H), 5.75 <com:Math><semantics>(1H,dd,J0.7,15.6,C23H),5.42(1H,d,J3.0,C6H),4.15(2H,dd,J7.1,14.2,OCH2CH3),<annotation encoding="application / x-tex">(1H, dd, J0.7, 15.6, C23H), 5.42 (1H, d, J3.0, C6H), 4.15 (2H, dd, J7.1, 14.2, OCH2CH3),< / annotation>< / semantics>< / com:Math> 4.11 (1H, app. t, J 2.8, C7H), 2.55-2.25 (3H, m), 2.14-2.00 (3H, m), 2.07 (3H, s, OAc).1.87- 1.11 (17H, m), 1.11 (3H, d, J 6.8, C21H<com:Sub>3< / com:Sub>), 0.81 (3H, s, CH<com:Sub>3< / com:Sub>) (see Figure 2). <com:Sup>13< / com:Sup>C NMR (100 MHz, CDCl<com:Sub>3< / com:Sub>): <com:Math><semantics>δ<annotation encoding="application / x-tex">\delta< / annotation>< / semantics>< / com:Math> = 198.9 (C=O), 168.7 (C=O), 166.9 (C=O),158.4 (C5), 154.0 (C22H), 131.9 (C4H), 119.3 (C23H), 76.5 (C6H), 61.2 (C7H), 60.1 (CH<com:Sub>2< / com:Sub>CH<com:Sub>3< / com:Sub>), 54.7 (CH), 50.8 (CH), 44.3 (CH), 42.6 (C), 39.6 (CH), 38.7 (CH<com:Sub>2< / com:Sub>), 37.6 (C), 36.8 (CH<com:Sub>2< / com:Sub>), 35.0 (CH), 34.1 (CH<com:Sub>2< / com:Sub>), 27.8 (CH<com:Sub>2< / com:Sub>), 23.1 (CH<com:Sub>2< / com:Sub>), 21.1 (CH<com:Sub>3< / com:Sub>C(O)), 20.5 (CH<com:Sub>2< / com:Sub>), 19.5 (CH<com:Sub>3< / com:Sub>CH<com:Sub>2< / com:Sub>), 19.2 (C21H<com:Sub>2< / com:Sub>), 14.3 (CH<com:Sub>3< / com:Sub>), 12.4 (CH<com:Sub>3< / com:Sub>) (see Figure 3). Synthesis of (6β, 7β, 22E)-6,7-epoxy-3-oxo-4,22-choladien-24-oic acid ethyl ester [Image disponible dans le document PDF, Image available in the PDF document] <com:Math><semantics>(6β,7α,22E)<annotation encoding="application / x-tex">(6\beta, 7\alpha, 22E)< / annotation>< / semantics>< / com:Math>-6-acetoxy-7-chloro -3-oxo-4,22-choladien-24-oic acid ethyl ester (48 mg) was dissolved in EtOH (5 mL) and K<com:Sub>2< / com:Sub>CO<com:Sub>3< / com:Sub> (32 mg) was added. The mixture was stirred at reflux for 4 h, then filtered and concentrated in vacuo, to give the desired crude β-epoxide in quantitative yield. Identity of the product was confirmed by <com:Sup>1< / com:Sup>H NMR and TLC comparison with data obtained for the compound (IA) prepared according to Example 1. Example 3 – Synthesis of <com:Math><semantics>(6β,7β,22E)<annotation encoding="application / x-tex">(6\beta, 7\beta, 22E)< / annotation>< / semantics>< / com:Math>-6,7-epoxy-3-oxo-4,22-choladien-24-oic acid ethyl ester (IA) using TCCA in formic acid [Image disponible dans le document PDF, Image available in the PDF document] (22E)-3-oxo-4,6,22-cholatrien-24-oic acid ethyl ester (1.0 g, 2.5 mmol) was dissolved in formic acid (10 mL). TCCA (235 mg) was added as a single portion and the solution stirred for 15 min. The mixture was diluted with EtOAc (100 mL) and washed with 5% aq. NaHSO<com:Sub>3< / com:Sub> (100 mL) followed by H<com:Sub>2< / com:Sub>O (2×50 mL). The organic layer was dried over Na<com:Sub>2< / com:Sub>SO<com:Sub>4< / com:Sub>, filtered and concentrated in vacuo. The residue was dissolved in EtOH (10 mL) and K2CO3 (698 mg, 5.05 mmol) was added. The mixture was stirred at 65 °C for 3 h and then concentrated in vacuo. Purification by column chromatography (SiO<com:Sub>2< / com:Sub>, eluting with heptane : EtOAc gradient) gave the desired (6β, 7β, 22E)-6,7-epoxy-3-oxo-4,22-choladien-24-oic acid ethyl ester (330 mg) as an off white solid. Identity of the product was confirmed by <com:Sup>1< / com:Sup>H NMR and TLC comparison with data obtained for the compound (IA) prepared according to Example 1. Example 4 – Synthesis of <com:Math><semantics>(6β,7β)<annotation encoding="application / x-tex">(6\beta, 7\beta)< / annotation>< / semantics>< / com:Math> and <com:Math><semantics>(6α,7α)<annotation encoding="application / x-tex">(6\alpha, 7\alpha)< / annotation>< / semantics>< / com:Math> mixture of <com:Math><semantics>(22E)<annotation encoding="application / x-tex">(22E)< / annotation>< / semantics>< / com:Math>-6,7-epoxy-3-oxo-4,22- choladien-24-oic acid ethyl ester using DBDMH in acetone / H<com:Sub>2< / com:Sub>O [Image disponible dans le document PDF, Image available in the PDF document] To a solution of (22E)-3-oxo-4,6,22-cholatrien-24-oic acid ethyl ester (396 mg, 1.0 mmol) in acetone: H<com:Sub>2< / com:Sub>O (9:1, 10 mL) at ambient temperature was added benzoic acid (61 mg, 0.5) mmol) followed by 1,3-dibromo-5,5-dimethylhydantoin (286 mg, 1 mmol) and the solution was stirred for 2 h. The mixture was diluted with EtOAc (50 mL) and washed with 5% aq. NaHSO<com:Sub>3< / com:Sub> (10 mL) and water (2×25 mL). The organic layer was dried over Na<com:Sub>2< / com:Sub>SO<com:Sub>4< / com:Sub>, filtered and concentrated in vacuo. The resulting yellow oil was dissolved in CH<com:Sub>2< / com:Sub>Cl<com:Sub>2< / com:Sub> (8 mL) and DBU (0. 5 mL) was added and the solution stirred for 16 h. The mixture was concentrated and the residue (dark brown oil) was purified by column chromatography (SiO<com:Sub>2< / com:Sub>, eluting with heptane: EtOAc gradient) to give (22E)-6,7-epoxy-3-oxo-4,22-choladien-24-oic acid ethyl ester as a 2:1 mixture of <com:Math><semantics>(6β,7β)<annotation encoding="application / x-tex">(6\beta,7\beta)< / annotation>< / semantics>< / com:Math> to <com:Math><semantics>(6α,7α)<annotation encoding="application / x-tex">(6\alpha,7\alpha)< / annotation>< / semantics>< / com:Math> epoxides (ratio based on integration of characteristic protons of CH4 in <com:Sup>1< / com:Sup>H NMR – see Figure 4) in 33% yield over two steps (137) mg, 0.33 mmol). Identity of the products in the mixture was confirmed by <com:Sup>1< / com:Sup>H NMR and compared with data obtained for the compound (IA) prepared according to Example 1 and its 6.7-alpha-epoxy isomer, which was previously synthesized following Uekawa et al. in Biosci. Biotechnol. Biochem. 2004, 68, 1332-1337 and synthesized XXX Example 5 – Synthesis of <com:Math><semantics>(6β,7β)<annotation encoding="application / x-tex">(6\beta, 7\beta)< / annotation>< / semantics>< / com:Math> and <com:Math><semantics>(6α,7α)<annotation encoding="application / x-tex">(6\alpha, 7\alpha)< / annotation>< / semantics>< / com:Math> mixture of <com:Math><semantics>6,7<annotation encoding="application / x-tex">6,7< / annotation>< / semantics>< / com:Math>-epoxy-3-oxo-4,22- choladien-24-oic acid ethyl ester using DBDMH in acetone / H<com:Sub>2< / com:Sub>O [Image disponible dans le document PDF, Image available in the PDF document] To a solution of (20S)-20-acetoxymethyl-pregna-4,6-dien-3-one (370 mg, 1.00 mmol) in acetone:H<com:Sub>2< / com:Sub>O (12 : 1, 5 mL) at ambient temperature was added 1,3-dibromo-5,5- dimethylhydantoin (229 mg, 0.80 mmol) in one portion and the solution was stirred for 1 h. A further portion of 1,3-dibromo-5,5-dimethylhydantoin was added (40 mg, 0.14 mmol) and after 10 min the mixture was diluted with EtOAc (50 mL), washed with 5% aq. NaHSO<com:Sub>3< / com:Sub> (25 mL) and 5% aq. NaHCO<com:Sub>3< / com:Sub> (25 mL). The organic phase was dried over anhydrous Na<com:Sub>2< / com:Sub>SO<com:Sub>4< / com:Sub>, filtered and concentrated in vacuo. The residue was purified by column chromatography (SiO<com:Sub>2< / com:Sub>, eluting with heptane : EtOAc gradient), to give 1.2 : 1 mixture of bromohydrins (102) mg, 0.22 mmol) (the ratio was calculated using characteristic peaks in <com:Sup>1< / com:Sup>H NMR). <com:Sup>1< / com:Sup>H NMR (400 MHz, CDCl<com:Sub>3< / com:Sub>): <com:Math><semantics>δ<annotation encoding="application / x-tex">\delta< / annotation>< / semantics>< / com:Math> = 5.95 (1H, s, C4H(a)), 5.86 (1.2H, s, C4H(b)), 4.59 (1H, d, J 2.6, C6H(a)), 4.47 (1.2H, d, J 2.8, C6H(b)), 4.30 (1.2H, app. t, J 2.7, C7H(b)), 4.10-4.04 (2.2H, m, <com:Math><semantics>CHAHBOAc<annotation encoding="application / x-tex">CH_AH_BOAc< / annotation>< / semantics>< / com:Math>), 4.04 (1H, app. t, J 2.2, C7H(a)), 3.82-3.76 (2.2H, m, <com:Math><semantics>CHAHBOAc<annotation encoding="application / x-tex">CH_AH_BOAc< / annotation>< / semantics>< / com:Math>), 3.13 (1.2H, br. s, OH(a)), 2.75 (1H, br. s, OH(b)), 2.60-1.02 (2.2H, m), 2.54-1.08 (57.2H, m), 0.80 (6.6H, s, CH<com:Sub>3< / com:Sub>). The isolated mixture of bromohydrins (72 mg, 0.15 mmol) was dissolved in <com:Math><semantics>CH2Cl2<annotation encoding="application / x-tex">CH_2Cl_2< / annotation>< / semantics>< / com:Math> (3 mL), DBU (50 µL) added and the solution stirred for 18 h. The mixture was concentrated in vacuo and the residue purified by column chromatography (SiO<com:Sub>2< / com:Sub>, eluting with heptane : EtOAc gradient) to give 1.2 : 1 mixture of <com:Math><semantics>(6β,7β)<annotation encoding="application / x-tex">(6\beta,7\beta)< / annotation>< / semantics>< / com:Math> to <com:Math><semantics>(6α,7α)<annotation encoding="application / x-tex">(6\alpha,7\alpha)< / annotation>< / semantics>< / com:Math> epoxides in quantitative yield (59 mg, 0.15 mmol). Examples 6-9 – Synthesis of <com:Math><semantics>(6α,5β)<annotation encoding="application / x-tex">(6\alpha, 5\beta)< / annotation>< / semantics>< / com:Math>-3,7-dioxo-6-ethyl-cholan-24-oic acid (VIAA) (precursor to obeticholic acid (OCA)) [Image disponible dans le document PDF, Image available in the PDF document] (VIAA) Example 6 – Synthesis of <com:Math><semantics>(6α,7β,22E)<annotation encoding="application / x-tex">(6\alpha, 7\beta, 22E)< / annotation>< / semantics>< / com:Math>-6-ethyl-7-hydroxy-3-oxo-4,22-choladien-24- oic acid ethyl ester (IVA) [Image disponible dans le document PDF, Image available in the PDF document] To a solution of ZnCl<com:Sub>2< / com:Sub> in THF (0.7 M, 31.2 mL, 21.8 mmol, 0.9 eq) was charged anhydrous THF (40 mL) and the contents then cooled to <com:Math><semantics>−10<annotation encoding="application / x-tex">-10< / annotation>< / semantics>< / com:Math> °C. A solution of EtMgBr in THF (1.0 M, 43.5 mL, 43.5 mmol, 1.8 eq) was added over 25 mins. Solid CuCl (240 mg, 2.6 mmol, 0.1 eq) was added in one portion and a solution of (6β, 7β, 22E)-6,7-epoxy-3-oxo-4,22- choladien-24-oic acid ethyl ester (IA) (10 g, 24.2 mmol) in THF (40 mL) was added dropwise over 15 mins. The reaction stirred for 1 h at −10 °C, (TLC 1:1 Heptane:EtOAc, visualised by UV and developed using Ceric Ammonium Molybdate stain) and then quenched by the dropwise addition of sat. aq. NH<com:Sub>4< / com:Sub>Cl (80 mL). The inorganic salts were filtered off, rinsed with TBME (100 ml) and the filtrate phases were separated. The organic phase was washed with sat. aq. NH<com:Sub>4< / com:Sub>Cl (80 mL) and 10% aqueous NaCl (80 mL). The organic phase was dried over Na<com:Sub>2< / com:Sub>SO<com:Sub>4< / com:Sub>, filtered and concentrated in vacuo at 40 °C. Purification by column chromatography (SiO<com:Sub>2< / com:Sub>, 0-50% Heptane : EtOAc) gave the title compound as a colourless oil solidifying on standing (9.6 g, 90% yield). <com:Sup>1< / com:Sup>H NMR (400 MHz, CDCl<com:Sub>3< / com:Sub>): <com:Math><semantics>δ<annotation encoding="application / x-tex">\delta< / annotation>< / semantics>< / com:Math> = 6.82 (1H, dd, <com:Math><semantics>J<annotation encoding="application / x-tex">J< / annotation>< / semantics>< / com:Math> = 15.6, 9.0, C22H), 5.84 (1H, d, <com:Math><semantics>J<annotation encoding="application / x-tex">J< / annotation>< / semantics>< / com:Math> = 1.6, C4H), 5.74 (1H, d, <com:Math><semantics>J=15.6<annotation encoding="application / x-tex">J = 15.6< / annotation>< / semantics>< / com:Math>, C23H), 4.17 (2H, q, <com:Math><semantics>J=7.1<annotation encoding="application / x-tex">J = 7.1< / annotation>< / semantics>< / com:Math>, OC<com:Math><semantics>H2<annotation encoding="application / x-tex">H_2< / annotation>< / semantics>< / com:Math>CH<com:Sub>3< / com:Sub>), 3.13 (1H, t, <com:Math><semantics>J=9.7<annotation encoding="application / x-tex">J = 9.7< / annotation>< / semantics>< / com:Math> C7H), 2.42-2.23 (4H, m), 2.05-0.89 (26H, m), 0.91 (3H, t, <com:Math><semantics>J=7.4<annotation encoding="application / x-tex">J = 7.4< / annotation>< / semantics>< / com:Math>, CH<com:Sub>3< / com:Sub>), 0.77 (3H, s, CH<com:Sub>3< / com:Sub>). <com:Sup>13< / com:Sup>C NMR (100 MHz, CDCl<com:Sub>3< / com:Sub>): <com:Math><semantics>δ<annotation encoding="application / x-tex">\delta< / annotation>< / semantics>< / com:Math> = 119.6, 169.1, 167.0, 154.2, 122.8, 119.3, 77.6, 60.2, 55.3, 54.1, 49.8, 48.2, 43.9, 43.1, 39.5, 39.4, 38.6, 35.3, 33.4, 28.5, 26.9, 21.5, 19.4, 18.9, 18.8, 14.3, 12.4, 10.7. (IR) v<com:Sub>max< / com:Sub>(cm<com:Sup>-1< / com:Sup>): 3473, 2937, 1716, 1650,1606. HRMS (ESI-TOF) <com:Math><semantics>m / z<annotation encoding="application / x-tex">m / z< / annotation>< / semantics>< / com:Math>: (M+H)<com:Sup>+< / com:Sup> calcd for C<com:Sub>28< / com:Sub>H<com:Sub>43< / com:Sub>O<com:Sub>4< / com:Sub> 443.3161; found: 443.3155. Example 7 – Synthesis of <com:Math><semantics>(5β,6α,7β)<annotation encoding="application / x-tex">(5\beta, 6\alpha, 7\beta)< / annotation>< / semantics>< / com:Math>-6-ethyl-7-hydroxy-3-oxo-cholan-24-oic acid ethyl ester (VA) [Image disponible dans le document PDF, Image available in the PDF document] 5% Pd / CaCO<com:Sub>3< / com:Sub> (1.2 g) was charged to a round bottom flask under an argon atmosphere followed by solution of <com:Math><semantics>(6α,7β,22E)<annotation encoding="application / x-tex">(6\alpha, 7\beta, 22E)< / annotation>< / semantics>< / com:Math>-6-ethyl-7-hydroxy-3-oxo-4,22-choladien-24-oic acid ethyl ester (IVA) (5.6 g) in DMF (25 mL). The mixture was cooled to −10 °C and the flask was evacuated then filled with hydrogen three times with vigorous stirring. The mixture was stirred under an atmosphere of hydrogen for 48 h while maintaining the temperature at -10 °C (IPC by TLC, eluent 1:1 EtOAc: Heptane; visualized with Anisaldehyde stain) then the flask was evacuated, filled with argon and filtered and the catalyst washed with TBME (100 mL). The filtrate was washed with 10% aq. NaCl (3 x 50 mL), dried over Na<com:Sub>2< / com:Sub>SO<com:Sub>4< / com:Sub>, filtered and concentrated in vacuo at 40 °C. Purification by column chromatography (SiO<com:Sub>2< / com:Sub>, 2-30% Heptane: EtOAc) gave (5<com:Math><semantics>β<annotation encoding="application / x-tex">\beta< / annotation>< / semantics>< / com:Math>, 6<com:Math><semantics>α<annotation encoding="application / x-tex">\alpha< / annotation>< / semantics>< / com:Math>, 7<com:Math><semantics>β<annotation encoding="application / x-tex">\beta< / annotation>< / semantics>< / com:Math>)-6-ethyl-7-hydroxy-3- oxo-cholan-24-oic acid ethyl ester (VA) in 89% yield (4.5 g). <com:Sup>1< / com:Sup>H NMR (400 MHz, CDCl<com:Sub>3< / com:Sub>): <com:Math><semantics>δ=4.12<annotation encoding="application / x-tex">\delta = 4.12< / annotation>< / semantics>< / com:Math> (2H, q, <com:Math><semantics>J=7.1<annotation encoding="application / x-tex">J = 7.1< / annotation>< / semantics>< / com:Math>, OCH<com:Sub>2< / com:Sub>CH<com:Sub>3< / com:Sub>), 3.23 (1H, app. t, <com:Math><semantics>J=8.4<annotation encoding="application / x-tex">J = 8.4< / annotation>< / semantics>< / com:Math> C7H), 2.38-0.93 (37H, m), 0.85 (3H, t, <com:Math><semantics>J=4.7<annotation encoding="application / x-tex">J = 4.7< / annotation>< / semantics>< / com:Math>, CH<com:Sub>3< / com:Sub>), 0.71 (3H, s). <com:Sup>13< / com:Sup>C NMR (100 MHz, CDCl<com:Sub>3< / com:Sub>): <com:Math><semantics>δ<annotation encoding="application / x-tex">\delta< / annotation>< / semantics>< / com:Math> = 212.0, 174.2, 75.1, 60.2, 56.0, 55.0, 45.2, 44.0, 43.7, 43.6, 40.1, 39.6, 37.7, 37.0, 36.6, 35.2, 34.7, 31.3, 31.0, 28.5, 26.8, 22.8, 21.9, 20.7, 18.4, 14.3, 12.2, 11.1. Example 8 – Synthesis of <com:Math><semantics>(5β,6α,)−3,7<annotation encoding="application / x-tex">(5\beta, 6\alpha,)-3,7< / annotation>< / semantics>< / com:Math>-dioxo-6-ethyl-cholan-24-oic acid ethyl ester (VIA) [Image disponible dans le document PDF, Image available in the PDF document] To a solution of <com:Math><semantics>(5β,6α,7β)<annotation encoding="application / x-tex">(5\beta, 6\alpha, 7\beta)< / annotation>< / semantics>< / com:Math>-6-ethyl-7-hydroxy-3-oxo-cholan-24-oic acid ethyl ester (VA) (2.4 g) in DMF (7 ml) and CH₃CN (7 mL) was added NaBr (111 mg) followed by AcOH (4.8 mL) and the mixture was cooled to 5 °C. A solution of sodium hypochlorite (~13% w / v, 4.5 mL) was added dropwise over 15 min, then the mixture was stirred for 1 h at 5 °C. Further CH<com:Sub>3< / com:Sub>CN (20 mL) was added at this point, as the mixture became dense, and the cooling bath removed. The mixture was allowed to stir at ambient temperature for 1 h, then further quantity of AcOH (3 mL) was added followed by a dropwise addition of sodium hypochlorite (~13% w / v, 3 mL). The reaction was stirred for 2 h at ambient temperature and a solution of aq. 5% w / v Na<com:Sub>2< / com:Sub>SO<com:Sub>3< / com:Sub> (360 mL) was charged dropwise with vigorous stirring, followed by EtOAc (150 mL). Phases were separated and the organic phase was washed wit...

Claims

1. A compound of general formula (la): [Image disponible dans le document PDF, Image available in the PDF document] (la) wherein: R 2 is H, halo, OH or a protected OH group; Y is a bond, or a C 1 − 20 C_{1-20} alkylene, C 2 − 20 C_{2-20} alkenylene or C 2 − 20 C_{2-20} alkynylene linker group any of which is optionally substituted with one or more R 3 ; wherein each R 3 is independently halo, OH, a protected OH group or NR 8 R 9 ; wherein each of R 8 and R 9 is independently H, C 1-6 alkyl, C(O)Ph, benzyl, phthalimide, tert-butyloxycarbonyl or carboxybenzyl; R 4 R^4 is C ( O ) O R 10 C(O)OR^{10} , O C ( O ) R 10 OC(O)R^{10} , C ( O ) N R 10 R 11 C(O)NR^{10}R^{11} , O R 10 OR^{10} , O S i ( R 13 ) 3 OSi(R^{13})_3 , S ( O ) R 10 S(O)R^{10} , S O 2 R 10 SO_2R^{10} , O S O 2 R 10 OSO_2R^{10} , S O 3 R 10 SO_3R^{10} , O S O 3 R 10 OSO_3R^{10} , halo, C N CN , N R 10 R 11 NR^{10}R^{11} , B R 10 R 11 BR^{10}R^{11} , C ( O ) C H 2 N 2 C(O)CH_2N_2 , − C H = C H 2 -CH=CH_2 , − C ≡ C H -C\equiv CH , C H [ C ( O ) O R 10 ] 2 CH[C(O)OR^{10}]_2 , C H ( B R 10 R 11 ) 2 CH(BR^{10}R^{11})_2 , azide, N O 2 NO_2 , N R 10 C ( O ) N R 10 S O 2 R 11 NR^{10}C(O)NR^{10}SO_2R^{11} , N R 10 C ( O ) N R 10 S O 2 N NR^{10}C(O)NR^{10}SO_2N R 10 R 11 , NR 10 SO 2 R 11 , C(O)NR 10 SO 2 R 11 , CH(XR 10 )(XR 11 ), CH(R 10 )(XR 11 ), phthalimide or a carboxylic acid mimetic group; wherein each X is independently O, S or NR 8 ; wherein each R 10 and R 11 is independently: a. hydrogen; or b. C 1 − 20 C_{1-20} alkyl, C 3 − 7 C_{3-7} cycloalkyl, C 2 − 20 C_{2-20} alkenyl or C 2 − 20 C_{2-20} alkynyl, any of which is optionally substituted with one or more substituents selected from: C 1 − 4 C_{1-4} alkyl, C 1 − 4 C_{1-4} haloalkyl, halo, N O 2 NO_2 , C N CN , O R 19 OR^{19} , S R 19 SR^{19} , C ( O ) O R 19 C(O)OR^{19} , C ( O ) N ( R 19 ) 2 C(O)N(R^{19})_2 , S O 2 R 19 SO_2R^{19} , O S O 2 R 19 OSO_2R^{19} , S O 3 R 19 SO_3R^{19} , O S O 3 R 19 OSO_3R^{19} , N ( R 19 ) 2 N(R^{19})_2 and a 6- to 14- membered aryl or 5- to 14-membered heteroaryl group, either of which is optionally substituted with one or more substituents selected from C 1-6 alkyl, C 1-6 haloalkyl, halo, NO 2 , CN, OR 19 , SR 19 , C ( O ) O R 19 C(O)OR^{19} , C ( O ) N ( R 19 ) 2 C(O)N(R^{19})_2 , S O 2 R 19 SO_2R^{19} , S O 3 R 19 SO_3R^{19} and N ( R 19 ) 2 N(R^{19})_2 ; or C. a 6- to 14- membered aryl, 5- to 14-membered heteroaryl group or 3- to 10- membered heterocyclic ring, any of which is optionally substituted with one or more substituents selected from: C 1-6 alkyl, C 3-7 cycloalkyl, C 1-6 haloalkyl, halo, NO 2 , CN, OR 19 , C ( O ) C 1 − 4 a l k y l C(O)C_{1-4}alkyl , S R 19 SR^{19} , C ( O ) O R 19 C(O)OR^{19} , C ( O ) N ( R 19 ) 2 C(O)N(R^{19})_2 , S O 2 R 19 SO_2R^{19} , S O 3 R 19 SO_3R^{19} , N(R 19 ) 2 , phenyl, 5- to 14-membered heteroaryl, 3- to 10-membered heterocyclic ring, methylenedioxy and ethylenedioxy; or d. a polyethylene glycol residue; or e. when R 4 R^4 is C ( O ) N R 10 R 11 C(O)NR^{10}R^{11} , C H ( X R 10 ) ( X R 11 ) CH(XR^{10})(XR^{11}) , N R 10 R 11 NR^{10}R^{11} , B R 10 R 11 BR^{10}R^{11} , CH[C(O)OR 10 ] 2 or CH(BR 10 R 11 ) 2 an R 10 and an R 11 group, together with the atom or atoms to which they are attached, may combine to form a 3- to 10- membered heterocyclic ring; wherein each R 19 is independently: H, C 1-6 alkyl, C 1-6 haloalkyl, or a 6- to 14- membered aryl or 5- to 14- membered heteroaryl group either of which is optionally substituted with one or more substituents selected from halo, C 1-6 alkyl and C 1-6 haloalkyl; and wherein each R 13 is independently: a. C 1 − 20 C_{1-20} alkyl, C 2 − 20 C_{2-20} alkenyl or C 2 − 20 C_{2-20} alkynyl, any of which is optionally substituted with one or more substituents selected from: halo, N O 2 NO_2 , C N CN , O R 19 OR^{19} , S R 19 SR^{19} , C ( O ) O R 19 C(O)OR^{19} , C ( O ) N ( R 19 ) 2 C(O)N(R^{19})_2 , S O 2 R 19 SO_2R^{19} , S O 3 R 19 SO_3R^{19} , O S O 3 R 19 OSO_3R^{19} , N ( R 19 ) 2 N(R^{19})_2 and a 6- to 14- membered aryl or 5- to 14-membered heteroaryl group, either of which is optionally substituted with one or more substituents selected from C 1-6 alkyl, C 1 − 6 C_{1-6} haloalkyl, halo, NO 2 , CN, OR 19 , SO 2 R 19 , SO 3 R 19 and N(R 19 ) 2 ; or b. a 6- to 14- membered aryl or 5- to 14-membered heteroaryl group either of which is optionally substituted with one or more substituents selected from: C 1 − 6 C_{1-6} alkyl, C 1 − 6 C_{1-6} haloalkyl, halo, N O 2 NO_2 , C N CN , O R 19 OR^{19} , S R 19 SR^{19} , C ( O ) O R 19 C(O)OR^{19} , C ( O ) N ( R 19 ) 2 C(O)N(R^{19})_2 , S O 2 R 19 SO_2R^{19} , S O 3 R 19 SO_3R^{19} and N ( R 19 ) 2 N(R^{19})_2 ; wherein each R 19 is independently: H, C 1 − 6 C_{1-6} alkyl or C 1 − 6 C_{1-6} haloalkyl; or Y and R 4 together form a =CH 2 group; and R 5 is H, OH or a protected OH group; or a salt or isotopic variant thereof.

2. A compound according to claim 1, wherein R 2 is H.

3. A compound according to claim 1 or claim 2, wherein Y is a bond or a C 1-3 alkylene 137 or C 2-3 alkenylene linker group, either of which is optionally substituted with one or two R 3 groups, wherein R 3 is as defined in claim 1 or claim 2.

4. A compound according to claim 3, wherein Y is -CH 2 CH 2 - or -CH=CH-.

5. A compound according to any one of claims 1 to 3, wherein R 3 is halo, OH, O C ( O ) R 14 OC(O)R^{14} , O S i ( R 16 ) 3 OSi(R^{16})_3 , or N R 8 R 9 NR^8R^9 ; wherein R 14 R^{14} is C 1 − 6 C_{1-6} alkyl or phenyl; each R 16 R^{16} is independently C 1-6 alkyl or phenyl; and each R 8 and R 9 is independently H, methyl, ethyl or tert-butoxycarbonyl.

6. A compound according to any one of claims 1 to 5, wherein R 4 is C(O)OR 10 , OR 10 , C ( O ) N R 10 R 11 C(O)NR^{10}R^{11} , S O 3 R 10 SO_3R^{10} , or O S O 3 R 10 OSO_3R^{10} .

7. A compound according to any one of claims 1 to 5, wherein R 4 is halo, CN, C H ( X R 10 ) ( X R 11 ) CH(XR^{10})(XR^{11}) , C H = C H 2 CH=CH_2 , − C = C H -C=CH , C H [ C ( O ) O R 10 ] 2 CH[C(O)OR^{10}]_2 , B R 10 R 11 BR^{10}R^{11} or Y and R 4 R^4 together form a =CH 2 group.

8. A compound according to claim 7, wherein R 4 is halo, CN, CH(OR 10 )(OR 11 ), CH=CH 2 , -C=CH, CH[C(O)OR 10 ] 2 , BR 10 R 11 or Y and R 4 together form a =CH 2 group.

9. A compound according to any one of claims 1 to 5, wherein R 4 is C(O)OR 10 , C O N R 10 R 11 CONR^{10}R^{11} , O S O 2 R 10 OSO_2R^{10} , O S O 3 R 10 OSO_3R^{10} , C N CN , azide, O R 10 OR^{10} , O S i ( R 13 ) 3 OSi(R^{13})_3 , C H [ ( C ( O ) O R 10 ) ] 2 CH[(C(O)OR^{10})]_2 , CH(OR 10 )(OR 11 ), NR 10 CONR 10 SO 2 R 11 and NR 10 SO 2 R 11 and tetrazole.

10. A compound according to any one of claims 1 to 5 wherein R 4 is C(O)OR 10 , O C ( O ) R 10 OC(O)R^{10} , O R 10 OR^{10} , O S i ( R 13 ) 3 OSi(R^{13})_3 , O S O 2 R 10 OSO_2R^{10} , halo, C N CN , N R 10 R 11 NR^{10}R^{11} , C H [ C ( O ) O R 10 ] 2 CH[C(O)OR^{10}]_2 , azide, C(O)NR 10 SO 2 R 11 CH(XR 10 )(XR 11 ); phthalimide, tetrazole or substituted tetrazole. A compound according to any one of claims 1 to 10, wherein each R 10 and R 11 is independently: a. hydrogen; or b. C 1 − 10 C_{1-10} alkyl, C 2 − 10 C_{2-10} alkenyl or C 2 − 10 C_{2-10} alkynyl, any of which is optionally substituted with one or more substituents selected from: C 1-4 alkyl, C 1-4 haloalkyl, halo, NO 2 , CN, OR 19 , SR 19 , C(O)OR 19 , C(O)N(R 19 ) 2 , SO 2 R 19 , O S O 2 R 19 OSO_2R^{19} , S O 3 R 19 SO_3R^{19} , O S O 3 R 19 OSO_3R^{19} , N ( R 19 ) 2 N(R^{19})_2 and a 6- to 14- membered aryl or 5- to 14-membered heteroaryl group, either of which is optionally substituted with one or more substituents selected from C 1-6 alkyl, C 1-6 haloalkyl, halo, NO 2 , CN, OR 19 , SR 19 , C(O)OR 19 , C(O)N(R 19 ) 2 , S O 2 R 19 SO_2R^{19} , S O 3 R 19 SO_3R^{19} and N ( R 19 ) 2 N(R^{19})_2 ; or C. a 6- to 10- membered aryl or 5 to 10-membered heteroaryl group either of which is optionally substituted with one or more substituents selected from: C 1 − 6 C_{1-6} alkyl, C 3 − 7 C_{3-7} cycloalkyl, C 1 − 6 C_{1-6} haloalkyl, halo, N O 2 NO_2 , C N CN , O R 19 OR^{19} , C ( O ) C 1 − 4 C(O)C_{1-4} alkyl, S R 19 SR^{19} , C ( O ) O R 19 C(O)OR^{19} , C ( O ) N ( R 19 ) 2 C(O)N(R^{19})_2 , S O 2 R 19 SO_2R^{19} , S O 3 R 19 SO_3R^{19} , N ( R 19 ) 2 N(R^{19})_2 , phenyl, 5- to 14-membered heteroaryl, 3- to 10-membered heterocyclic ring, methylenedioxy and ethylenedioxy; or d. a polyethylene glycol residue; or e. when R 4 is C(O)NR 10 R 11 , CH(XR 10 )(XR 11 ), NR 10 R 11 or BR 10 R 11 , an R 10 and an R 11 group, together with the atom or atoms to which they are attached, may combine to form a 3- to 10-membered heterocylic ring.

12. A compound according to any one of claims 1 to 10, wherein each R 10 and R 11 is independently: a. hydrogen; or b. C 1 − 10 C_{1-10} alkyl, C 2 − 10 C_{2-10} alkenyl or C 2 − 10 C_{2-10} alkynyl, any of which is optionally substituted with one or more substituents selected from halo, NO 2 , CN, OR 19 , SR 19 , C(O)OR 19 , C ( O ) N ( R 19 ) 2 C(O)N(R^{19})_2 , S O 2 R 19 SO_2R^{19} , S O 3 R 19 SO_3R^{19} , O S O 3 R 19 OSO_3R^{19} , N ( R 19 ) 2 N(R^{19})_2 and a 6- to 14- membered aryl or 5- to 14-membered heteroaryl group, either of which is optionally substituted with one or more substituents selected from C 1-6 alkyl, C 1-6 haloalkyl, halo, NO 2 , CN, OR 19 , SR 19 , C(O)OR 19 , C ( O ) N ( R 19 ) 2 C(O)N(R^{19})_2 , S O 2 R 19 SO_2R^{19} , S O 3 R 19 SO_3R^{19} and N ( R 19 ) 2 N(R^{19})_2 ; or C. a 6- to 10- membered aryl or 5- to 10-membered heteroaryl group either of which is optionally substituted with one or more substituents selected from: C 1 − 6 C_{1-6} alkyl, C 1 − 6 C_{1-6} haloalkyl, halo, N O 2 NO_2 , C N CN , O R 19 OR^{19} , S R 19 SR^{19} , C ( O ) O R 19 C(O)OR^{19} , C ( O ) N ( R 19 ) 2 C(O)N(R^{19})_2 , S O 2 R 19 SO_2R^{19} , S O 3 R 19 SO_3R^{19} and N ( R 19 ) 2 N(R^{19})_2 ; or d. a polyethylene glycol residue; or e. when R 4 is C(O)NR 10 R 11 , CH(OR 10 )(OR 11 ), CH(SR 10 )(SR 11 ), NR 10 R 11 or BR 10 R 11 , an R 10 and an R 11 group, together with the atom or atoms to which they are attached, may combine to form a 3- to 10-membered heterocylic ring.

13. A compound according to any one of claims 1 to 12, wherein R 10 is hydrogen; or C 1 − 6 C_{1-6} alkyl or C 2 − 6 C_{2-6} alkenyl, either of which is optionally substituted with phenyl.

14. A compound according to any one of claims 1 to 5, wherein R 4 is C(O)OR 10 , OR 10 , SO 3 R 10 , OSO 3 R 10 , halo, CN, CH(XR 10 )(XR 11 ), CH[C(O)OR 10 ] 2 or BR 10 R 11 ;and each R 10 and R 11 R^{11} is independently H, C 1 − 6 C_{1-6} alkyl or benzyl; or, when R 4 is CH(OR 10 )(OR 11 ) or BR 10 R 11 , R 10 and R 11 together with the atom or atoms to which they are attached, may combine to form a 3 to 10-membered heterocyclic ring; or R 4 is C(O)NR 10 R 11 substituted with C(O)OR 19 , OR 19 , SO 3 R 19 , or OSO 3 R 19 and R 19 is H.

15. A compound according to claim 14, wherein X is O.

16. A compound according to any one of claims 1 to 15, wherein R 5 is H.

17. A process for preparing a compound of general formula (la) according to any one of claims 1 to 16 comprising: reacting a compound of general formula (IIa) with a halogenating agent followed by reaction with base: [Image disponible dans le document PDF, Image available in the PDF document] wherein Y, R 2 , R 4 and R 5 are as defined in any one of claims 1 to 16.

18. A process according to claim 17, wherein the halogenating agent is Br 2 , Cl 2 , l 2 , N- bromosuccinimide (NBS), N-chlorosuccinimide (NCS), N-iodosuccinimide (NIS), chloramine-T (tosylchloramide), tert-butylhypochlorite, trichloroisocyanuric acid (TCCA), tribromoisocyanuric acid (TBCA), triiodoisocyanuric acid (TICA), 1,3-dichloro-5,5- dimethylhydantoin (DCDMH), 1,3-dibromo-5,5-dimethylhydantoin (DBDMH), 1,3-diiodo- 5,5-dimethylhydantoin (DIDMH), di-tert-butyl peroxide with TiCl 4 ; Ca(OCl) 2 with NaCl in AcOH; or TMSCI with H 2 O 2 H_2O_2 .

19. A process according to claim 18, wherein the halogenating agent is trichloroisocyanuric acid (TCCA), tribromoisocyanuric acid (TBCA), triiodoisocyanuric acid (TICA), 1,3-dichloro-5,5-dimethylhydantoin (DCDMH), 1,3-dibromo-5,5-dimethylhydantoin (DBDMH), or 1,3-diiodo-5,5-dimethylhydantoin (DIDMH).

20. A process according to claim 18, wherein the halogenating agent is trichloroisocyanuric acid (TCCA) or tert-butylhypochlorite.

21. A process according to any one of claims 18 to 20, wherein the halogenating agent is trichloroisocyanuric acid (TCCA).

22. A process according to any one of claims 18 to 21, wherein the reaction is carried out in a solvent selected from acetone, DMF, MeCN CH 2 Cl 2 , THF, t-butyl alcohol, acetic acid, dioxane, DMSO, formic acid and water, and mixtures thereof.

23. A process according to claim 22, wherein the reaction is carried out in a solvent selected from acetone, water, formic acid, acetic acid and mixtures thereof.

24. A compound of general formula (IIIxa): [Image disponible dans le document PDF, Image available in the PDF document] (IIIxa) or a salt or isotopic variant thereof, wherein X is Cl, Br or I; and wherein Y, R 2 , R 4 and R 5 are as defined in any one of claims 1 to 16; or A compound of general formula (IIIya): [Image disponible dans le document PDF, Image available in the PDF document] (IIIya) or a salt or isotopic variant thereof, wherein X is Cl, Br or I; and wherein Y, R 2 , R 4 and R 5 are as defined in any one of claims 1 to 16.

25. A mixture comprising a compound of general formula (IIIxa) and a compound of general formula (IIIya), as defined in claim 24.

26. A process for preparing a compound of general formula (Xa): [Image disponible dans le document PDF, Image available in the PDF document] (Xa) or a salt or an isotopic variant thereof, wherein, R 1 R^1 is C 1 − 4 C_{1-4} alkyl, C 2 − 4 C_{2-4} alkenyl or C 2 − 4 C_{2-4} alkynyl optionally substituted with one or more substituents selected from halo, OR 6 and NR 6 R 7 ; wherein each of R 6 R^6 and R 7 R^7 is independently H or C 1 − 4 C_{1-4} alkyl; R 2 is H, halo or OH; R 5a is H or OH; and Y 1 Y^1 is a bond, or a C 1 − 20 C_{1-20} alkylene linker group which is optionally substituted with one or more R 3 ; or Y 1 Y^1 and R 4 R^4 together form a =CH 2 group; wherein R 3 and R 4 are as defined in any one of claims 1 to 16; the process comprising the steps of: (a) selective alkylation of a compound of general formula (Ia) having the formula: [Image disponible dans le document PDF, Image available in the PDF document] (la) wherein R 2 , R 4 , R 5 and Y are as defined in claim 1; with an organometallic regent to give a compound of general formula (IVa): [Image disponible dans le document PDF, Image available in the PDF document] (IVa) wherein R 1 is as defined for a compound of general formula (Xa); and Y, R 2 , R 4 and R 5 are as defined in claim 1; (b) reducing the compound of general formula (IVa) using a suitable reducing agent to give a compound of general formula (Va): [Image disponible dans le document PDF, Image available in the PDF document] (Va) wherein Y 1 and R 1 are as defined for a compound of general formula (Xa); and R 2 , R 4 and R 5 are as defined in claim 1; (c) oxidising the compound of general formula (Va) using a suitable oxidising agent to give a compound of general formula (VIa): [Image disponible dans le document PDF, Image available in the PDF document] (Vla) wherein Y 1 and R 1 are as defined for a compound of general formula (Xa);and R 2 , R 4 and R 5 are as defined in claim 1; (d) reduction of the compound of general formula (VIa) using a suitable reducing agent and, where R 2 and / or R 5 is a protected OH, removal of the protecting group(s), to give a compound of general formula (Xa) as defined above, wherein removal of the protecting group can take place before or after the reduction.

27. A process according to claim 26, which further includes one or more steps of converting compounds of general formulae (Ia), (IVa), (Va), (VIa) and (Xa) to other compounds of general formulae (Ia), (IVa), (Va), (VIa) and (Xa).

28. A process according to claim 27, wherein the one or more steps of converting compounds consist of reacting the side chains of the compounds of general formulae (Ia), (IVa), (Va), (VIa), and (Xa) to arrive at compounds with alternative Y / Y 1 and / or R 4 moieties.

29. A compound of general formula (IVa): [Image disponible dans le document PDF, Image available in the PDF document] (IVa) or a salt or isotopic variant thereof, wherein R 1 is C 1-4 alkyl, C 2-4 alkenyl or C 2-4 alkynyl optionally substituted with one or more substituents selected from halo, OR 6 and NR 6 R 7 ; wherein each of R 6 and R 7 is independently H or C 1-4 alkyl; and wherein Y, R 2 , R 4 and R 5 are as defined in any one of claims 1 to 16.

30. A compound of general formula (Va): [Image disponible dans le document PDF, Image available in the PDF document] (Va) or a salt or isotopic variant thereof, wherein R 1 is C 1-4 alkyl, C 2-4 alkenyl or C 2-4 alkynyl optionally substituted with one or more substituents selected from halo, OR 6 and NR 6 R 7 ; wherein each of R 6 and R 7 is independently H or C 1-4 alkyl; Y 1 Y^1 is a bond, or a C 1 − 20 C_{1-20} alkylene linker group which is optionally substituted with one or more R 3 ; or Y 1 and R 4 together form a =CH 2 group; wherein R 2 , R 3 , R 4 and R 5 are as defined in any one of claims 1 to 16.

31. A compound of general formula (IIIxz): [Image disponible dans le document PDF, Image available in the PDF document] (IIIxz) or a salt an isotopic variant thereof, wherein X is Cl, Br or I; R 40 R^{40} is C(O)H, C(O)C 1-4 alkyl, C(O)phenyl, C(O)benzyl, phenyl, benzyl, C 2-4 alkene or SO 2 CF 3 ; wherein C(O)phenyl, C(O)benzyl, phenyl and benzyl are optionally substituted with one or more substituents selected from C 1-4 alkyl, OC 1-4 alkyl, halo, nitro, C 1-4 haloalkyl and OC 1-4 haloalkyl; and wherein Y, R 2 , R 4 and R 5 are as defined in any one of claims 1 to 16.

32. A compound of general formula (IIIyz): [Image disponible dans le document PDF, Image available in the PDF document] (IIIyz) or a salt or an isotopic variant thereof, wherein X is Cl, Br or I; R 40 R^{40} is C(O)H, C(O)C 1-4 alkyl, C(O)phenyl, C(O)benzyl, phenyl, benzyl, C 2-4 alkenyl, or SO 2 CF 3 ; wherein C(O)phenyl, C(O)benzyl, phenyl and benzyl are optionally substituted with one or more substituents selected from C 1-4 alkyl, OC 1-4 alkyl, halo, nitro, C 1-4 haloalkyl and OC 1-4 haloalkyl; and wherein Y, R 2 , R 4 and R 5 are as defined in any one of claims 1 to 16.

33. A compound of general formula (la) selected from: (6β, 7β, 22E)-6,7-epoxy-3-oxo-4,22-choladien-24-oic acid ethyl ester (Example 1); (6β, 7β, 20S)-6,7-epoxy-3-oxo-4,22-choladien-24-oic acid ethyl ester (Example 5); (6β, 7β, 20S)-6,7-epoxy-20-hydroxymethyl-pregna-4-en-3-one (Example 41); (6β, 7β, 20S)-6,7-epoxy-20-bromomethyl-pregna-4-en-3-one (Example 42); (20S)-methanesulfonyloxymethyl-6,7-β-epoxy-4-pregnen-3-one (Example 43); (20R)-cyanomethyl-6,7-β-epoxy-4-pregnen-3-one (Example 44); (20S)-20-acetoxymethyl-6,7-β-epoxy-pregna-4-en-3-one (Example 45); (6β, 7β, 20S)-6,7-epoxy-20-tert-butyldiphenylsiloxymethyl-pregna-4-en-3-one (Example 46); (6β, 7β, 20S)-6,7-epoxy-20-azidomethyl-pregna-4-en-3-one (Example 47); (6β, 7β, 20S)-6,7-epoxy-20-(N-phthalimidomethyl)-pregna-4,6-dien-3-one (Example 48); (6β, 7β, 20S)-6,7-epoxy-20-formyl-pregna-4-en-3-one (Example 49); (6β, 7β, 20S)-6,7-epoxy-20-(ethylenedioxymethyl)-pregna-4-en-3-one (Example 50); and (6β, 7β)-6,7-epoxy-3-oxo-4-cholen-23-carboxy-24-oic acid dimethyl ester (Example 51); or a salt or isotopic variant thereof.