Intermediary compounds for hemisynthesis of taxanes and preparation of them

Description

The invention relates to novel intermediates of semisynthetic taxanes and to a process for their preparation. Taxanes are natural compounds known as anticancer agents, the diterpene skeleton of which is usually esterified with a β-amino acid ol-5 chain of N-alkyl or N-aryl phenyl isoserine derivatives. There are dozens of taxanes isolated from yews (Taxus) of the genus Taxus, such as PACLITAXEL (R^Ac, R2=Ph, R3=R4=H), cephalomannin, their 10-deacetylated derivatives or baccatins 10 (these derivatives without side chains), represented by the general formula (1) and (2), respectively. French researchers attempted to isolate PACLITAXEL from the regenerating parts (leaves) of T. baccata, the European yew, in order not to quickly exhaust the original source of the compound, Taxus brevifolia. They thus suggested that the precursor for the biogenesis of taxanes is 10-desacetylbaccatin III, which is an excellent starting point for semisynthesis, as it occurs relatively abundantly in the leaf extract. 20 The semisynthesis of taxanes, such as PACLITAXEL or DOCETAXEL (R-|=Ac, R2=tert-butoxy, R3=R4=H) therefore consists of esterification of a protected derivative of baccatin or 10-desacetylbaccatin III with a β-amino acid derivative at the 13-position. 25 Various modern semi-syntheses of PACLITAXEL or DOCETAXEL have already been reported (EP-0 253 738, EP-0 336 840, EP-0 336 841, EP-0 495 718, WO 92 / 09589, WO 94 / 07877, WO 94 / 07878, WO 94 / 07879, WO 94 / 10169, WO 94 / 12482, 30 EP-0 400971, EP-0 428376, WO 94 / 14787). Two recent publications by Georg, I., Chen, TT, Ojima, I. and Vyas, DM ["Taxane Anticancer Agents, Basic Science and Current Status", ÁCS Symposium Series 583, Washington (1955)] and especially 35 Suffness, M. ["TAXOL® Science and Applications CRC Press (1955)] and the 1500 references cited therein provide an exhaustive review of the semi-syntheses of taxanes. The β-amino acid side chains of PACLITAXEL or DOCETAXEL, N-alkyl or N-aryl phenyl isoserine derivatives, have a (2R,3S) configuration, and one of the main difficulties in the semisynthesis of taxanes is the preparation of a pure enantiomer product. The first task is to prepare a pure enantiomer of the phenyl isoserine derivatives used in the semisynthesis of taxanes. The second task is to maintain this enantiomer purity during the esterification of the baccatin derivative and subsequent treatments of the resulting products (removal of hydroxy-protecting groups, etc.). Several reports on asymmetric synthesis using β-amino acid derivatives 50 focus on the chemistry of isoserine and its derivatives, β-amino acids with a cyclic, dehydrated form of β-lactam (EP-0 525 589). Most of the syntheses of phenyl isoserine derivatives that can be used as precursors for the side chain of taxanes revolve around a common intermediate, (2R,3R)-cis-8-phenylglycidic acid, which is then converted to β-phenyl isoserine with ammonia (EP-0 495718) or a nucleophile [Gou et al., J. Org. Chem., 58, 1287-1289 (1983)]. In order to obtain β-phenylisoserine of (2R,3S) configuration, these different processes require a large number of reaction steps, necessarily with a racemate resolution step - carried out by conventional selective crystallization methods - either in the case of cis^-phenylglycidic acid or β-phenylisoserine, or later, after transformation. In addition, various methods have been proposed to preserve the enantiomeric purity of the side chain precursor of the taxanes during the esterification of the baccatin derivative, in particular by using ring intermediates with a fixed configuration, which avoid the risk of isomerization during the esterification reaction carried out under vigorous conditions. In more detail, it concerns β-lactam (EP-0400 971), oxazolidine (WO 92 / 09589, WO 94 / 07877, WO 94 / 07878, WO 94 / 07879, WO 94 / 10169, WO 94 / 12482), oxazinone (EP-0 428 376), or oxazoline derivatives (WO 94 / 14787).These ring precursors are prepared starting from the corresponding β-phenylisoserine derivative. Even in the latter case, the proposed methods for the preparation of the side chain precursors of the desired taxanes consist of a large number of steps and a necessary racemate resolution. Therefore, it was important to develop a new synthetic method for the side chain precursor intermediates of the taxanes, in particular the enantiomers of ac / s-8-phenylglycidic acid, β-phenylisoserine and their ring derivatives. Finally, in the semisynthesis of taxanes, in particular PACLITAXEL, the only suitable baccatin derivative used to date is one in which the 7-hydroxy group is protected by a trialkylsilyl group (EP-0 336 840, WO 94 / 14787), the removal of which is carried out exclusively in acidic media. It was therefore also important to use new hydroxy protecting groups which allow selective protection of the 7-hydroxy group, which also allow a wider range of deprotection conditions. The invention relates primarily to an improved process for the preparation of side chain precursors of taxanes. The invention relates to the conversion of a cis-aryl glycidate of the general formula (I) - in which Ar is an aryl, typically a phenyl group, and R is a hydrocarbon group, preferably a straight or branched alkyl group or optionally a cycloalkyl group substituted with one or more alkyl groups - by a Ritter reaction in which the 8-N-(alkylamido)- and α-hydroxy groups or their ring precursors are introduced in a regio- and stereospecific manner in one step. Depending on the reaction medium, two types of Ritter reaction are distinguished: the first leads directly to the fully functionalized, straight form of the chain by opening the oxetane ring, the second leads to the direct formation of an oxazoline. The symbol "*" indicates the presence of an asymmetric carbon atom in (R)- or (S)-configuration. The Ritter reaction is stereospecific in both cases, with retention of the configuration at C-2 and inversion of the configuration at C-3.The process within the scope of the invention is advantageously carried out on one of the enantiomers of the cis-aryl glycidate derivative of general formula (I). HU 225 507 B1 is carried out in such a way that it is not necessary to resolve the racemate at the end to obtain the corresponding enantiomer of the resulting open-chain compound or the oxazoline. In the preparation method of the cis-6-aryl glycidate derivative of the general formula (I) described below, R represents an optically pure enantiomer of a highly sterically chiral hydrocarbon group, preferably a cycloalkyl, especially cyclohexyl group substituted with one or more alkyl groups. R is therefore preferably an enantiomer of the menthyl group, especially the (+)-menthyl group. 1. Direct synthesis of the open side chain The direct synthesis of the straight chain by the Ritter reaction means that a cis-p-aryl glycidate derivative of the general formula (I) as defined above is reacted with a nitrile of the general formula (VII) - in which R2 is an aryl, preferably phenyl group - in the presence of a protonic acid such as sulfuric acid, perchloric acid, hydrogen [tetrafluoroborate] and water. Then, the β-aryl isoserine of general formula (lla) - in which Ar, R and R2 are defined as above - is obtained. The reaction involves the inversion of the configuration of the C-3 carbon atom of the cis-6-phenylglycidate derivative. In this way, starting from a (2R,3R)-cis-6-phenylglycidate derivative, the corresponding derivative of the β-aryl isoserine with the (2R,3S) configuration is obtained. The Ritter reaction is carried out in a suitable solvent at a temperature between -75 °C and +25 °C. Suitable solvents may be the nitrile itself, if it is liquid at the reaction temperature, or the acid itself (sulfuric acid, perchloric acid, or hydrogen tetrafluoroborate), or a solvent such as methylene chloride or diethyl ether. Conventionally used protonic acids may contain the amount of water necessary for hydrolysis. If benzonitrile (R2=phenyl) is reacted with a (2R,3R)-configuration cis-aryl glycidate, in which Ar is a phenyl group, the corresponding derivative of the general formula (IIa) - in which Ar and R2 are phenyl groups - with a (2R,3S) configuration β-aryl isoserine is directly obtained, which is none other than the precursor of the side chain of PACLITAXEL. 2. Direct synthesis of the cyclic side chain In the case of this second variant, a Ritter reaction is also carried out in the presence of a Lewis acid - in particular boron trifluoride-acetic acid complex, boron trifluoride etherate, antimony pentachloride, tin tetrachloride, titanium tetrachloride, etc. - or a protonic acid, such as hydrogen tetrafluoroborate, of the general formula (VII') - in which R'2 is the previously defined R or a lower alkyl or lower perhaloalkyl group, such as trichloromethyl, with a nitrile, and the reaction is carried out in an anhydrous medium. As in the synthesis of the open-chain compound, the solvent can be the nitrile itself, if it is a liquid at the reaction temperature, or a suitable solvent such as methylene chloride or diethyl ether. The reaction temperature is also between -75 °C and +25 °C. In the absence of water, an intramolecular Ritter reaction occurs, and the general formula (I Ib) - in which Ar, R and R'2 has the meaning given above - oxazoline is obtained. As in the Ritter reaction carried out in the presence of water, the reaction involves an inversion of the configuration of the C-3 carbon atom of the cis-6-phenylglycidate derivative. In this way, starting from a (2R,3R)-cis-6-phenylglycidate derivative, the corresponding derivative of the oxazoline with the (2R,3S) configuration is obtained. To avoid the formation of a free carbocation, which can cause a number of possible secondary reactions, the addition of reagents in the two types of Ritter reactions is preferably carried out in the following order: i) first a complex is formed between the nitrile and the acid, then ii) the acid catalyst is added to the mixture of oxirane and nitrile. The products obtained in this first step, the β-aryl isoserine of formula (lla) or the oxazoline of formula (llb), can be further converted in an optional second step, described below, or can be converted to the acid by mild saponification before coupling with a protected baccatin derivative for the semisynthesis of taxanes, in particular PACLITAXEL and its 10-deacetylated derivatives or DOCETAXEL. In the case of the β-aryl isoserine derivatives of formula (lla), saponification can be preceded by protection of the hydroxyl group with a suitable protecting group. In this way, a compound of general formula (II'a) is obtained - in which Ar, R and R2 are as defined above, GP represents the hydroxy protecting group of the hydroxy group suitable for the synthesis of taxanes, more specifically the alkoxy ether, aralkoxy ether, aryloxy ether groups, or the haloalkoxycarbonyl group, such as the methoxymethyl, 1-ethoxyethyl, benzyloxy, [6-(trimethylsilyl)ethoxy]methyl group, or the tetrahydropyranyl, β-alkoxycarbonyl group (TrOC), the β-halogenated or alkylsilylated ethers or the alkoxyacetyl, aryloxyacetyl, haloacetyl or formyl groups. 3. Optional transformation of compounds of formula (lla) or (llb) The compounds of formula (lla) or (llb) previously obtained can optionally be converted into new intermediates, precursors of the side chain in the semisynthesis of taxanes. These transformations involve the retention of the configuration of the C-2 and C-3 carbon atoms. The new intermediates obtained will therefore have the same stereochemistry as the compounds of formula (lla) or (llb) from which they are prepared. The products obtained in this second step are then converted into acids by mild saponification before coupling them with a protected baccatin derivative for the semisynthesis of taxanes, in particular PACLITAXEL and / or DOCETAXEL. 3.1 Cyclization of compounds of general formula (lla) Compounds of formula IIa can then be converted to oxazolines of formula IIb by conventional methods (WO 94 / 14787). HU 225 507 B1 The β-aryl isoserine derivatives of general formula (lla) can also be converted to the derivatives of general formula (lll'a) in which Ar and R are defined as above, and R”2 is as defined above, R'2 is an alkoxy, preferably tert-butoxy, or a straight or branched chain alkyl containing at least one unsaturated bond, for example a 1-methyl-1-propylene group, and the corresponding dialkyl acetals are used to form cyclic oxazolidinone intermediates. The oxazolidinones of the general formula (IIIa) are obtained by first reacting a β-aryl isoserine derivative of the general formula (IIa) with a (haloalkoxy)carbonyl, especially (2,2,2-trichloroethoxy)carbonyl (TrOC) ester, followed by cyclization in the presence of a strong organic base such as diazabicycloundecene (DBU). Thus, an oxazolidinone derivative of the general formula (IIIa) is obtained, in which Ar and R are as defined above. The compounds of general formula (IIIa) can also be prepared by direct synthesis by reacting the β-aryl glycidate derivatives of general formula (II'a) with urea. The acylated derivatives of general formula (III'a) are obtained by introducing the R”-CO group by conventional methods of acylation, suitable acylating agents being - for example, of the general formula R"-CO-X, in which R" is as defined above and X is a halogen atom, an acid halide or the corresponding acid anhydride - in the presence of. Dialkyl acetals are obtained by conventional methods of acetal formation. 3.2 Ring opening of oxazolines of general formula (llb) Hydrolysis of oxazolines of general formula (llb) in acidic medium gives compounds of general formula (lllb) - in which Ar, R and R'2 are defined as above, the β-aryl isoserine derivative is obtained. When R'2 is a lower perhaloalkyl group, such as trichloromethyl, R'2-CO preferably forms the protecting group for the hydroxy function. Thus, this precursor of the side chain of taxanes can be converted to the general formula (lll'b) - in which Ar, R, R'2 and R2 are defined as above - amide. In this way, we can prepare both the precursor of the side chain of PACLITAXEL (R”2=phenyl) and DOCETAXEL (R”2=tert-butoxy). 4. Preparation of the cis-arylglycidic acid derivative of general formula (I) The cis-arylglycidic acid derivative of the general formula (I) can be prepared by conventional modern methods or by simple esterification of the cis-arylglycidic acid with the corresponding general alcohol ROH. In order to improve the overall yield of the synthesis of side chain precursors of taxanes, the process of the present invention provides for the conversion of an aldehyde of the general formula (VIII) to a compound of the general formula (IX) - in which Ar, R are defined as above, and X is a halogen, especially a chlorine or bromine atom, reacting with haloacetate to produce a compound of general formula (I) - in which Ar is defined as above, and R represents an optically pure enantiomerically pure aryl glycidate derivative of a highly spherically hindered hydrocarbon group. Preferably, the optically pure enantiomer of the highly spherically hindered chiral hydrocarbon group is a cycloalkyl group substituted with one or more alkyl, especially cyclohexyl groups. A Darzens reaction takes place, whereby a mixture of two diastereomers, the (2R,3R)- and (2R,3S)-cis-arylglycidic acid esters and one enantiomer of an optically pure chiral alcohol of the general formula R-OH is obtained, because the Darzens reaction with a sterically highly hindered haloacetate leads mainly to the ac-form β-arylglycidate. Preferably, the sterically highly crowded chiral hydrocarbon group is chosen to allow the physical separation of the two diastereomers from the reaction mixture, for example by selective crystallization, without the need for stereoselective separation of the desired enantiomer at the end of the reaction by conventional crystallization methods or on a chiral column. The alcohol of general formula R-OH is preferably menthol, one of the rare, economical and highly sterically hindered chiral alcohols commercially available in both enantiomeric forms. In the preparation process of a side chain precursor of taxanes, a (2R,3R)-cis-aryl glycidate is desired. In this case, the sterically highly hindered chiral hydrocarbon group is chosen such that the (2R,3R)-cis-phenyl glycidate crystallizes first from the reaction mixture. If the alcohol of the general formula R-OH is menthol, (+)-menthol is preferably used. The asymmetric Darzens reaction is carried out in the presence of a base, in particular an alkali metal alcohol, such as potassium tertiary butyrate or an amide, such as lithium tert-butylate, in a suitable solvent, in particular an ether, such as diethyl ether, at a temperature of between -78°C and +25°C. The reaction, which leads to a diastereomeric mixture consisting almost exclusively of acylglycidates, can achieve a yield of more than 95%, around 97%. Treatment of the isolated product with a suitable solvent, in particular a methanol-water mixture, makes it possible to easily achieve the physical separation of the desired diastereomers. Fractional (double) crystallization achieves rapid enrichment of the desired diastereomer, with diastereomer purity greater than 99%. This latter point is particularly important because it controls the isomeric purity of the final taxane product, as the unwanted diastereomers exert their own biological activity, different from that of the desired taxane. It is important to note that the selective use of the two enantiomers of the menthyl ester allows us to obtain two diastereomeric precursors of the two enantiomers of the glycidic acid ester by the same process. HU 225 507 B1 In addition to the fairly high yield (reaching 45%) of the pure, isolated diastereomer, the diastereomeric purity of the main product of the reaction, the ease of carrying out the reaction, the simplicity and speed of purification, and the low cost of reagents and catalysts make the industrial synthesis of this key intermediate in the asymmetric synthesis of β-amino acids easy to carry out and economical. If a compound of formula (I) obtained by an asymmetric Darzens reaction is used in the process within the scope of the invention, the compounds of formula (IIa), (II'a), (IIb), (IIIa), (IIIb) and (III'b) as defined above are obtained, in which R is an optically pure enantiomer of a highly spherically hindered chiral hydrocarbon group, such as a cycloalkyl group substituted by one or more alkyl, especially cyclohexyl, groups, preferably menthyl, preferably (+)-menthyl. The invention also relates to these compounds, which are useful as intermediates in the synthesis of the side chain of taxanes. 20 It should be emphasized that the method is a very rapid, 3-step approach to substituted, chiral oxazolines, already described in the literature (WO 94 / 14787), from commercially available compounds, instead of 6-8. 5. Gentle soaping The mild saponification of compounds of general formula (IIa), (II'a), (IIb), (IIIa), (IIIb) and (IIIb'b) is carried out under mild conditions, for example in the presence of alkali metal carbonate in a methanol / water mixture, in such a way as to release the acid function while preserving the structure of said compounds. After gentle saponification, the compounds of the general formula (IIa), (II'a), (IIb), (IIIa), (IIIb) and (III'b) defined above - where R represents a hydrogen atom - are obtained, which can be directly used for the semisynthesis of taxanes when coupled with a suitable baccatin III derivative. 6. Semisynthesis of taxanes 40 6.1 Esterification The invention also relates to a process for the preparation of a compound of general formula (IV) - in which formula C is a side chain selected from the group consisting of (lla-1), (ll'a-1), (llb-1), (llla-1), (ΙΙΓ-1), (lllb-1) and (lll'b-1) groups, in which groups Ar, R2, R'2, R2, R3 and GP are defined as above, and B is a group of general formula (V) derivable from baccatin II (wherein Ac is an acetyl group, 50 Bz means benzoyl group, Me means methyl group, R4 is an acetyl group or a protecting group for the hydroxy function of GP1, and R5 is the protecting group of the GP2 hydroxy function) - 55 for the semisynthesis of taxanes, by esterification of a suitable baccatin III derivative of general formula (V) carrying a hydroxy group at the C-13 position with one of the groups of general formula (lla-1), (ll'a-1), (llb-1), (llla-1), (lll'a-1), (lllb-1) or (lll'b-1) defined above (wherein R is 60 hydrogen atoms), under conditions customary for the preparation of taxanes, as described in the art (EP-0 253 738, EP-0 336 840, EP-0 336 841, EP-0 495 718, WO 92 / 09589, WO 94 / 07877, WO 94 / 07878, WO 94 / 07879, WO 94 / 10169, WO 94 / 12482, EP-0 400971, EP-0 428376, WO 94 / 14787). The protecting groups GP1 and GP2 are independently conventional groups used in the semisynthesis of taxanes, for example trialkylsilyl (EP-0 336 840) or TrOC (EP-0 336 841). GP1 and GP2 are each independently a highly sterically sterically straight or branched (haloalkoxy)carbonyl group containing at least one halogen atom. Preferably, the alkyl part of these groups contains 1-4 carbon atoms and 3 or 4 halogen atoms, preferably the (2,2,2-tribromoethoxy)carbonyl, (1,2,2,2-tetrachloroethoxy)carbonyl, (2,2,2-trichlorotert-butoxy)carbonyl and (trichloromethoxy)carbonyl groups, all of which have a higher sterically sterically sterically than the (T rOC)-(haloalkoxy)carbonyl group used to protect taxanes in the 7-position. GP1 and GP2 both independently mean acyl groups containing at least one oxygen atom on their α-carbon atom relative to the carbonyl group. These acyl groups are described in particular in EP-0 445 021. Preferred are alkoxyacetyl or (aryloxy)acetyl groups of the general formula (a) - in which Rg represents a spherically hindered alkyl, cycloalkyl or aryl group, or (arylidenedioxy)acetyl groups of the general formula (b) - in which Ar" represents an arylidene group. A spherically hindered alkyl group preferably means a C1-6 straight or branched alkyl group substituted with one or more bulky groups selected from halogen atoms, C1-6 straight or branched alkyl, C1-6 straight or branched alkoxy, C3-6 cycloalkyl or aryl groups. For example, a tertiary butyl or triphenylmethyl group. Cycloalkyl is preferably a cycloalkyl group having 3 to 6 carbon atoms, optionally substituted by one or more bulky groups selected from halogen atoms, straight or branched chain alkyl having 1 to 6 carbon atoms, straight or branched chain alkoxy having 1 to 6 carbon atoms, aryl groups. Cyclohexyl groups substituted by one or more straight or branched chain alkyl having 1 to 6 carbon atoms, such as the menthyl group, its racemate or enantiomers and mixtures thereof in any ratio are preferred. Aryl preferably means a phenyl, naphthyl, anthryl or phenanthryl group, optionally substituted with one or more bulky groups selected from halogen atoms, C1-6 straight or branched alkyl, C1-6 straight or branched alkoxy or aryl, especially phenyl groups. A phenyl group, optionally substituted with one or more bulky groups in the ortho and ortho' positions to the ether bond, is preferred. HU 225 507 B1 Finally, an arylidene group is preferably a phenythine, naphthylene, anthrylene or phenanthrylene group, optionally substituted by one or more halogen atoms, C1-6 straight or branched alkyl, C1-6 straight or branched alkoxy or aryl, in particular phenyl groups. GP1 and GP2 are both independently a trialkylgermanyl group, or together they form a divalent group of general formula (c) - in which R7 and R8 are both independently a high-volume alkyl group, defined in the same manner as above, preferably R7 and R8 are both isopropyl groups. 6.2 Possible ring opening When C is a group of formula (IIb-1) or (IIIa-1), the oxazoline ring opening is carried out to obtain taxane derivatives of formula (VI) in which Ac, Bz, Me, Ar, R2, R4 and R5 are as defined above. The ring opening of the groups of formula (llb-1), (llla-1) and (lll'a-1) is generally carried out in acidic or basic media. In the case of the group of formula (llb-1), in order to obtain the compound of formula (VI), this ring opening can be carried out in acidic media according to what is described in the art (preferably WO 94 / 14787), followed by treatment with basic media. 6.3 Removal of the protecting group Finally, the removal of the hydroxy protecting group of the compounds of formula (V) and (VI) is carried out by replacing the hydroxy protecting group GP [where C is a group of formula (II'a-1)], the hydroxy protecting group GP1 (where R4 is different from acetyl) and the hydroxy protecting group GP2 with a hydrogen atom by conventional methods. The deprotection of compounds of formula (V) - in which C is a group of formula (IIb-1) or (IIIa-1) and GP1 and / or GP2 are independently conventional groups used in the semisynthesis of taxanes, for example trialkyl groups - occurs simultaneously with the ring opening described above. If GP1 and / or GP2 are bulky (haloalkoxy)carbonyl groups, the removal of the protecting groups is carried out by the usual methods described for the removal of TrOC, with zinc or heavy metals, for example zinc contaminated with copper, in an organic solvent, preferably acetic acid, tetrahydrofuran or ethanol, in the presence or absence of water. If GP1 and / or GP2 are acyl groups containing at least one oxygen atom on the α-carbon atom to the carbonyl group, the deprotection is carried out in a basic medium at low temperature, preferably in methanol, at a temperature lower than 10 °C, preferably around 0 °C. In the case where C is a group of general formula (IIb-1), the ring opening of the oxazoline in a basic medium occurs simultaneously with the removal of the protecting group, thus in one step the compound of general formula (VI) in which R4 is acetyl or hydrogen and R5 is hydrogen, leading to a taxane derivative, in contrast to the ring opening in acidic media described in the art, which requires a second step in a basic medium. The known protecting groups are removed by known methods and, if present, the oxazoline ring is opened by hydrolysis to give taxanes identical in all respects to the authentic taxanes. For example, by way of illustration of the invention, but without limiting the scope of the invention, PACLITAXEL, 10-desacetyltaxol, cephalomannin and DOCETAXEL can be obtained from the corresponding protected derivatives. The removal of acyl protecting groups containing at least one oxygen atom on their α-carbon atom relative to the carbonyl group was first attempted under the conditions traditionally considered mildest, i.e., by refluxing zinc acetate in methanol. In this case, when the reaction was completed within a few hours (in contrast to the several days observed for acetates), in addition to the desired compound, its C-7-epimer was isolated in all cases, which is the result of the classical equilibrium of retroaldolization. Assuming that under neutral or even slightly acidic conditions the main causes of this are methanol and especially temperature, we returned to the usual conditions for the removal of acyl groups described by previous authors, in basic medium, ethanol, at low temperature. Under these conditions, no significant epimerization was observed.As an example, PACLITAXEL, 10-desacetyltaxol, cephalomannin and DOCETAXEL, which are identical in all respects to the authentic taxanes, were obtained from the corresponding alkoxy- or aryloxyacetylated derivatives. Finally, it should be noted that all previously described methods aimed at improving the overall yield of the semi-synthesis involve the preliminary synthesis of the phenylisoserine side chain in order to convert it into one of the aforementioned ring structures (β-lactams, oxazolidines or oxazolines). Thus, paradoxically, the apparently best implementations of the coupling of these ring structures merely compensate for the overall yield reduction caused by the coupling of the ring-forming sequence to the open-chain synthesis sequence (i.e., 9 steps in total). With the general taxane synthesis method of the present invention, a product, such as PACLITAXEL, is obtained in only 5 steps: - (1S,2R,5S)-(+)-menthyl-(2R,3R)-3-phenyl glycidate; - (1S,2R,5S)-(+)-menthyl-(4S,5R)-2,4-diphenyl-4,5-dihydroxazole-5-carboxylate; - saponification; - semi-synthesis (esterification); - ring opening and deprotection. Finally, the invention relates to the synthetic intermediates of general formulae (IV), (V) and (VI) described above, which are used in the general synthesis of the taxanes of the invention. In general, a hydrocarbon group is preferably saturated or unsaturated (tar6) according to the invention. HU 225 507 B1 is understood to mean a hydrocarbon group (which may contain one or more unsaturations), such as a straight or branched chain, optionally unsaturated alkyl group, optionally unsaturated cycloalkyl group, aralkyl or aryl group - each of which may be optionally substituted with one or more substituents, in particular alkyl groups. A straight or branched alkyl group within the scope of the invention preferably means an alkyl group having 1 to 6 carbon atoms, in particular methyl, ethyl, propyl, isopropyl, butyl and various branched isomers thereof, such as tert-butyl, pentyl and hexyl and various branched isomers thereof. This definition also applies to the alkyl parts of alkoxy or aralkoxy groups. Within the scope of the invention, a cycloalkyl group preferably means a cycloalkyl group having 3 to 6 carbon atoms, in particular a group selected from cyclopropyl, cyclobutyl, cyclopentyl or cyclohexyl groups. Within the scope of the invention, a group preferably means an aromatic or heteroaromatic group, in particular a group selected from phenyl, naphthyl, anthryl, phenanthryl, pyridyl, pyrimidyl, etc. groups. Finally, halogen is preferably understood to mean chlorine, bromine or iodine. Haloalkoxycarbonyl groups are preferably groups whose alkyl part contains 1 to 4 carbon atoms and 3 or 4 halogen atoms. The general synthesis method of the taxanes of the present invention is summarized in Scheme [A], in which R is (+)-menthyl and R2 or R'2 is phenyl. Examples of substituents in Scheme [A] include: Ar=phenyl; R=benzoyl, thigloyl, tert-butoxycarbonyl; GP^ GP2=trialkylgermanyl, haloalkoxycarbonyl, alkoxyacetyl; GP=protecting group. The final step in the semisynthesis of taxanes according to the invention is summarized in Schemes [B] and [C]. Scheme [B] outlines the synthesis of PACLITAXEL starting from the compounds of formula (IV) defined above [wherein C is a group of formula (IIb-1) or (III'a-1)]. Scheme [C] outlines the synthesis of 10-desacetyltaxol starting from a compound of formula (IV) [wherein C is a group of formula (IIb-1)]. In the reaction schemes, GP-1, GP2=triethylgermanyl, 2,2,2-trichlorotert-butoxycarbonyl group; Bz=benzoyl; Ac=acetyl, Ph=phenyl; Me=methyl group. The same synthetic schemes can of course be applied to other substituents. Experimental part I. Side chain precursors of taxanes Example 1 (1S, 2R, 5S)-(+)-Menthyl-(chloroacetate) To a solution of 100 g (0.640 mol) of (1S,2R,5S)-(+)-menthol in 1 L of anhydrous methylene chloride at room temperature, 57 ml (0.704 mol) of anhydrous pyridine were added with stirring. After stirring for a few minutes, 56 ml (0.704 mol) of (chloroacetyl) chloride were added and the reaction was allowed to continue for another 30 minutes. After thin-layer chromatography, 50 g of crushed ice were added and the reaction mixture was stirred vigorously for 1 hour. After dilution with 100 ml of methylene chloride, the organic phase was washed several times with 200 ml of saturated aqueous sodium chloride solution, dried over magnesium sulfate, and then evaporated under reduced pressure. After chromatography of the crude product obtained in this way on silica gel (particle size 15-40 pm; eluent=cyclohexane:ethyl acetate, volume ratio=20:1), 146 g of (1 S,2R,5S)-(+)-menthyl-(chloroacetate) of formula (P1) are obtained in the form of a syrup. Characteristic properties of the obtained compound:1H-NMR spectrum (400 MHz; CDCl3) (chemical shifts δ, ppm; coupling constants J, Hz): 4.77 (1H, dt); 4.06 and 4.02 (2H, 2d, J=13.6); 2.02 (1H, m, J=11.8); 1.87 (1H, m, J=7 and 2.6); 1.69 (2H, m); 1.50 (1H, m); 1.43 (1H, m, J=11.7 and 3); 1.07 (1H, m); 1.02 (1H, q, J=11.8); 0.92 and 0.90 (6H, 2d, J=6.4); 0.89 (1H, m); 0.77 (3H, d, J=7). Example 2 (1S, 2R, 5S)-(+)-Menthyl-(2R, 3R)-3-phenylglycidate To a solution of 152 g (0.653 mol) of (1S,2R,5S)-(+)-menthyl-(chloroacetate) in 600 ml of anhydrous diethyl ether at room temperature, 69 ml (0.686 mol) of benzaldehyde are added with stirring. After stirring for a few minutes, the solution is cooled to -78 °C under an inert atmosphere, then a suspension of 85 g (0.718 mol) of potassium tert-butylate in 400 ml of anhydrous diethyl ether is added over 2 hours and the reaction mixture is allowed to warm to room temperature. After thin-layer chromatography, the organic phase is diluted with 200 ml of methylene chloride, washed several times with saturated aqueous sodium chloride solution, dried over magnesium sulfate and concentrated under reduced pressure. In this way, 200 g of crude product are obtained in the form of a syrup containing four diastereomers (two of which are cis and two are trans), which is subjected in this state to fractional crystallization. First, a solution of the crude product 2 in methanol heated to 160 °C, to which 700 ml of osmotically purified water is gradually added, is left to stand for 16 hours at room temperature and without shaking. The lower, yellow solid phase rich in the franc isomer is discarded, and the colorless crystals of the upper phase rich in the cis isomer are separated by filtration. The crystals thus obtained are redissolved in 2 I of methanol heated to 60 °C, 500 ml of osmotically purified water are added until constant turbidity is achieved, and the mixture is left to stand for 16 hours at room temperature. Three additional crystallizations using the same method, but with reduced volumes of methanol (1 L) and water (200 mL), were required to obtain 23 g of crystalline (1S,2R,5S)-(+)-menthyl-(2R,3R)-3-phenylglycidate of formula (P2) with HPLC purity better than 99%. The characteristic properties of the resulting compound are: Melting point: 104 °C. HU 225 507 Β11H-NMR spectrum (400 MHz; CDCl3) (chemical shifts δ, ppm; coupling constants J, Hz): 7.40 (2H, dd, J=7.8 and 1.7); 7.32 (3H, m); 4.58 (1H, dt, J=10.9 and 4.2); 4.26 (1H, d, J=4.6); 3.83 (1H, d, J=4.8); 1.6-0.85 (9H, m); 0.78 (3H, d, J=7); 0.75 (3H, d, J=6.4); 0.62 (3H, d, J=6.9). X-ray diffraction study of a single crystal of (1S,2R,5S)-(+)-menthyl-(2R,3R)-3-phenylglycidate for the indirect determination of its absolute configuration: The single crystal was obtained from a crystal suspension formed by adding a precipitant (water) to a warm, semi-saturated methanolic glycidate solution. Upon slow cooling, fine needles of 99.95% purity (HPLC) were precipitated from the solution, which were stored in a wet state until final isolation. The selected sample (fine, 0.12*0.12x0.40 mm needle) was examined with an ENRAF-NONIUS CAD4 type automatic diffractometer (molybdenum radiation graphite monochromator). The cell parameters were obtained by refining the ensemble of 25 reflections recorded at a high theta (Θ) angle. The data collection [(20max=50°, scan ω / 2θ=1; duration tmax=60 seconds; HKL range: H: 0-6, K: 0-14, L: 0-28; intensity control: no significant deviation (0.1%)] yielded 1888 reflections, of which 1037 were accepted: Ι>1.5σ (I). Molecular formula; CigH26O3; molecular weight=302.42, orthorhombic, P212121, a=5.709 (11), b=12.908 (4), c=24.433 (8) A, V=1801 (5) A3, Z=4, Dx=1.116 Mg.rrr3, λ(ΜοΚα)=0.70926 A, μ=0.69 cm1, F(000)=656, T=294 K, final R factor=0.072 - from 1037 observations. After Lorenz and polarization corrections, the structure was solved using the direct method, which allowed the localization of most of the non-hydrogen atoms; the others were placed by repeated difference Fourier synthesis. After isotropic (R=0.125) and then anisotropic (R=0.095) refinement, the positions of most of the hydrogen atoms were determined by difference Fourier synthesis (between 0.39 and 0.14 e / Å3), the others were placed by calculation. The entire structure was refined using the full matrix method - which leads to factors R=0.080, Rw=0.072; and Sw=1.521 (residual electron contribution Δρ<=0.21 e / Å3) {x, y, z, β,ρ for C and O; X, Y, Z for H; 200 variables and 1037 observations; w=1 / a (Fo2)2=[a2(l)+(0.04Fo2)2]-i / 2}. The atomic scattering factors are taken from the Tables Internationales de Cristallographie [International Tables for X-ray Crystallography (1974). Vol. IV. Birmingham: Kynoch Press, (currently distributed by D. Reidel, Dordrecht)]. The calculations were performed on a Hewlett Packard 9000-710 computer for the structure determinations according to [SHELDRICK, GM Crystallographic Computing 3: Data Collection, Structure Determination, Proteins and Databases, eds.: Sheldrick, GM, C. Krüger and R. Goddard. Oxford: Clarendon Press (1985)], and for the other calculations according to the MÓLÉN program package [FAIR, CK MÓLÉN, interactive intelligent system for crystal structure analysis. Enraf-Nonius, Delft, Netherlands (1990)]. The ORTEP diagram [JOHNSON, CK: ORTEP Report ORNL-3794; Oak Ridge National Laboratory Tennessee, USA (1965)] is shown in Figure [D]. A sample of (1 S,2R,5S)-(+)-menthyl-(2R,3R)-3-phenylglycidate in methanol treated with sodium methylate gave the corresponding methyl (phenylglycidate) with the following characteristics: [α]2 = +12° (c = 1.15; chloroform). 1H-NMR spectrum (400 MHz; CDCl3) (chemical shifts δ, ppm; coupling constants J, Hz): 7.40 (2H, d, J=8); 7.32 (3H, m); 4.26 (1H, d, J=4.6); 3.84 (1H, d, J=4.6); 3.55 (3H, s). Example 3 (1S,2R,5S)-(+)-Menthyl-(4S,5R)-2,4-diphenyl-4,5-dihydrooxazole-5-carboxylate Under an inert atmosphere, to a stirred solution of 30 g (0.0993 mol) of (1S,2R,5S)(+)-menthyl-(2R,3R)-3-phenylglycidate and 305 ml (2.98 mol) of benzonitrile in 5 L of anhydrous methylene chloride at -65 °C was added 10 ml (0.109 mol) of 54% hydrogen [tetrafluoroborate] in diethyl ether over 10 min. The reaction was allowed to proceed for one hour at -65 °C and, after thin layer chromatography, 300 ml of saturated aqueous sodium bicarbonate solution was added and allowed to warm to room temperature with stirring. After extraction of the aqueous phase with methylene chloride (2*200 ml), the combined organic phases are extracted with saturated sodium chloride solution (200 ml), water (50 ml) and dried over magnesium sulfate. After evaporation under reduced pressure and removal of the residual benzonitrile under high vacuum at 50 °C, the crude product obtained is purified by chromatography on silica gel (particle size 15-40 pm; eluent=cyclohexane:ethyl acetate; volume ratio: 20:1). In this way, 32 g of colorless syrup (production: 80%) (P3) (1S,2R,5S)-(+)-menthyl-(4S,5R)-2,4-diphenyl-4,5-dihydrooxazole-5-carboxylate is isolated, which shows the following characteristic properties:1H-NMR spectrum (400 MHz; CDCl3) (chemical shifts δ, ppm; coupling constants J, Hz): 8.10 (2H, d J=7.1); 7.54 (1H, t, J=7.4); 7.46 (2H, t, J=7.4); 7.34 (5H, m); 5.40 (1H, d, J=6.4); 4.88 (1H, d, J=6.4); 4.85 (1H, dt, J=10.9 and 4.4); 2.09 (1H, m); 1.84 (1H, m, J=7 and 2.7); 1.71 (1H, m); 1.69 (1H, m); 0.9 (1H, m); 0.85 (3H, d, J=7); 0.77 (3H, d, J=7). Example 4 (4S, 5R)-2,4-Diphenyl-4,5-dihydrooxazole-5-carboxylic acid At room temperature, to a solution of 3.5 g (8.64 mmol) of (1 S,2R,5S)(+)-menthyl-(4S,5R)-2,4-diphenyl-4,5-dihydrooxazole-5-carboxylate in 70 ml of methanol, 6 g (43.2 mmol) of potassium carbonate in osmotized water are added with stirring, and the reaction is allowed to proceed for one hour at room temperature. After thin-layer chromatography, the reaction medium is evaporated under reduced pressure. The aqueous phase thus obtained is washed with methylene chloride (3*100 ml), acidified to pH 2 by adding 20 ml of aqueous 1 M hydrochloric acid solution, and extracted with ethyl acetate (3*100 ml). The combined organic HU 225 507 Β1 extracts are dried with magnesium sulfate and evaporated under reduced pressure. In this way, 2.26 g (yield=98%) of (4S,5R)-2,4-diphenyl-4,5-dihydrooxazole-5-carboxylic acid of formula (P4) are obtained in the form of a colorless powder, which exhibits the following characteristic properties: [α]d = +27.7° (c = 0.99; CH2Cl2:MeOH = 1:1). Melting point = 201-202 °C. 1H-NMR spectrum (400 MHz; DMSO-d6) (chemical shifts δ, ppm; coupling constants J, Hz): 7.99 (2H, d, J=7.3); 7.64 (1H, t, J=7.4); 7.55 (2H, t, J=7.7); 7.36 (5H, m); 5.40 (1H, d, J=6.3); 4.99 (1H, d, J=6.4)5. Example (1S,2R,5S)-(+)-Menthyl-(2R,3S)-N-benzoyl-3phenyl-isoserinate g (2.47 mmol) (1S,2R,5S)-(+)-menthyl-(4S,5R)2,4-diphenyl-4,5-dihydrooxazole-5-carboxylate prepared in 15 ml of methanol and 15 ml of tetrahydrofuran was added to a solution of 15 ml of 1 M aqueous hydrochloric acid solution with stirring at room temperature. The reaction mixture was boiled for 1 hour and, after monitoring by thin layer chromatography and cooling to room temperature, saturated sodium bicarbonate solution (45 ml) was gradually added until a basic pH was reached. After stirring at room temperature for 48 hours, the aqueous phase obtained by concentration under reduced pressure was extracted with methylene dichloride (100 ml).The organic phase is washed with saturated sodium chloride solution (2*50 ml), dried with magnesium sulfate, evaporated under reduced pressure, and the resulting residue is purified by chromatography on silica gel (particle size 15-40 pm; eluent=methylene dichloride:methanol; volume ratio: 95:5). In this way, 0.835 g (yield=80%) of (1S,2R,5S)-(+)-menthyl(2R,3S)-N-benzoyl-3-phenyl-isoserinate of formula (P5) is obtained as a colorless solid product, which shows the following characteristic properties:1H-NMR spectrum (400 MHz; CDCl3) (chemical shifts δ, ppm; coupling constants J, Hz): 7.77 (2H, d J=7.2); 7.51 (1H, t, J=7.3); 7.45 (2H, m); 7.36 (2H, t, J=7.2); 7.29 (2H, t, J=7.2); 7.04 (1H, d, J=9.2); 5.78 (1H, dd, J=9.2 and 2.1); 4.79 (1H, dt, J=10.9 and 4.4); 4.63 (1H, sz); 3.35 (1H, w s); 1.81 (2H, m); 1.67 (3H, m); 1.5-1.36 (2H, m); 1.09-0.91 (2H, m); 0.89 (3H, d, J=6.9); 0.77 (3H, d, J=6.5); 0.74 (3H, d, J=6.9). Example 6 (1S,2R,5S)-(+)-Menthyl-(2R,3S)-N-benzoyl-3-phenyl-O(triethylsilyl)-isoserinate To a solution of 0.8 g (1.89 mmol) of (1S,2R,5S)-(+)-menthyl-(2R,3S)N-benzoyl-3-phenylisoserinate in 10 ml of anhydrous methylene chloride was added 0.255 g (2.08 mmol) of 4-(dimethylamino)pyridine with stirring. After stirring for a few minutes at room temperature, 477 µl (2.84 mmol) of (triethylsilyl) chloride was added over 5 minutes. After stirring for one hour at room temperature and monitoring by thin layer chromatography, the reaction mixture was diluted with 100 ml of methylene chloride. The organic phase was washed with saturated aqueous sodium bicarbonate solution (2*20 ml), saturated aqueous sodium chloride solution (50 ml), dried over magnesium sulfate and concentrated under reduced pressure. After chromatography on silica gel (particle size 15-40 pm) (eluent=cyclohexane:ethyl acetate; volume ratio: 10:1) of the formula (P6) (1S,2R,5S)-(+)-menthyl-(2R,3S)-N-benzoyl-3-phenyl-O-(triethylsilyl)-isoserinate, 0.74 g (yield=75%) was obtained as a colorless syrup. The characteristic properties of the resulting compound are: 1H-NMR spectrum (400 MHz; CDCl3) (chemical shifts δ, ppm; coupling constants J, Hz): 7.82 (2H, d J=7); 7.52 (1H, t, J=7.4); 7.45 (2H, t, J=7); 7.37 (2H, d, J=7.2); 7.32 (2H, t, J=7.2); 7.26 (2H, m); 5.60 (1H, dd); 4.73 (1H, dt, J=11 and 4.3); 1.88-1.67 (2H, m); 1.44 (2H, m); 1.06-0.87 (m); 0.80 (m); 0.67 (3H, d, J=7); 0.62-0.34 (m). Example 7 (2R,3S)-N-Benzoyl-3-phenyl-O-(triethylsilyl)-isoserine At room temperature, to a solution of 0.5 g (0.931 mmol) of (1S,2R,5S)-(+)-menthyl-(2R,3S)-N-benzoyl-3-phenyl-O-(triethylsilyl)-isoserine in 15 ml of methanol, a solution of 0.644 g (4.655 mmol) of sodium carbonate in 10 ml of osmotized water is added while stirring. After stirring at room temperature for 16 hours and checking by thin layer chromatography, the reaction medium is evaporated under reduced pressure and the remaining aqueous phase is washed with methylene chloride (3*50 ml) and then acidified to pH 2 by slow addition of aqueous 1 M hydrochloric acid solution (10 ml). The aqueous phase was extracted with ethyl acetate (3 x 50 ml), the combined organic phases were dried over magnesium sulfate and evaporated under reduced pressure. In this way, 0.320 g (yield=90%) of (2R,3S)-N-benzoyl-3-phenyl-O-(triethylsilyl)-isoserine of formula (P7) is obtained in the form of a colorless powder, the characteristic properties of which are as follows: 1H-NMR spectrum (400 MHz; DMSO-d6) (chemical shifts δ, ppm; coupling constants J, Hz): 8.46 (1H, d, J=9.3); 7.82 (2H, d J=7.1); 7.54 (1H, t, J=7.2); 7.47 (2H, m); 7.36 (1H, t); 7.32 (2H, t); 5.44 (1H, dd, J=9.2 and 5.5); 4.64 (1H, d, J=5.6); 0.77 (9H, m); 0.45 (6H, m). Example 8 (1S, 2R, 5S)-(+)-Menthyl-(2R, 3S)-N-benzoyl-3phenyl-O-[(2,2,2-trichloroethoxy)carbonyl]-isoserinate To a solution of 1.38 g (3.3 mmol) of (1S, 2R, 5S)-(+)-menthyl-(2R, 3S)N-benzoyl-3-phenyl-isoserinate in 30 ml of anhydrous methylene chloride, 480 mg (3.96 mmol) of 4-(dimethylamino)pyridine were added under inert atmosphere with stirring. After stirring for 10 minutes at room temperature, 540 µl (3.96 mmol) of (2,2,2-trichloroethoxy)carbonyl chloride were added over 5 minutes. After stirring for two hours at room temperature and monitoring by thin layer chromatography, the organic phase was extracted with saturated aqueous sodium bicarbonate solution (2*10 ml), saturated aqueous sodium chloride solution (10 ml) HU 225 507 Β1 is washed, dried with magnesium sulfate and evaporated under reduced pressure. After chromatography of the resulting residue on silica gel (particle size 15-40 pm) (eluent=cyclohexane:ethyl acetate; volume ratio=5:1), 1.60 g (yield=82%) of (1S,2R,5S)-(+)-menthyl-(2R,3S)N-benzoyl-3-phenyl-O-[(2,2,2-trichloroethoxy)carbonyl]-isoserinate of formula (P8) is obtained as a colorless syrup. The characteristic properties of the resulting compound are as follows: 1H-NMR spectrum (400 MHz; CHCl3-d) (chemical shifts δ, ppm; coupling constants J, Hz): 7.82 (2H, d J=7.4); 7.53 (1H, t, J=7.4); 7.44 (4H, m); 7.35 (2H, t, J=7); 7.29 (1H, t, J=7); 7.09 (1H, d, J=9.3); 6.0 (1H, dd, J=9.3 and 2.5); 5.45 (1H, d, J=2.6); 4.78 and 4 72 (2H, 2d, J=11.9); 4.77 (1H, m); 1.85 (1H, m); 1.79 (1H, m); 1.65 (2H, m); 1.43 (1H, m); 1.02 (1H, m); 0.96 (1H, m); 0.86 (1H, m); 0.83 (3H, d, J=7); 0.78 (3H, d, J=6.5; 0.68 (3H, d, J=6.9). Example 9 (1S,2R,5S)-(+)-Menthyl-(4S,5R)-4-phenyloxazolidin-2-one-5-carboxylate Under an inert atmosphere, 1 ml (7.28 mmol) of 1,8-diaza-bicyclo[5.4.0]undec-7-ene was added to a solution of 3.96 g (6.62 mmol) of (1 S,2R,5S)(+)-menthyl-(2R,3S)-N-benzoyl-3-phenyl-O-[(2,2,2trichloroethoxy)carbonyl]-isoserinate in 30 ml of anhydrous methylene chloride at room temperature with stirring. After stirring at room temperature for 30 minutes, the organic phase was washed with 10 ml of saturated aqueous sodium chloride solution, dried over magnesium sulfate and evaporated under reduced pressure. After purification of the residue by chromatography on silica gel (particle size 15-40 pm) (eluent=cyclohexane:ethyl acetate; volume ratio=7:3), 2.18 g (yield: 95%) of the title compound (P9) were obtained as a yellow syrup. The characteristic properties of the resulting compound are: 1H-NMR spectrum (400 MHz; CHCl3-d) (chemical shifts δ, ppm; coupling constants J, Hz): 7.40 (5H, m); 6.09 (1H, s); 4.93 (1H, d, J=5.3); 4.86 (1H, dt, J=11.9 and 4.4); 4.73 (1H, d, J=5.4); 2.05 (1H, m); 1.81 (1H, m); 1.71 (2H, m); 1.54-1.41 (3H, m); 1.107 (2H, m); 0.94 (3H, d, J=6.5); 0.88 (3H, d, J=7); 0.77 (3H, d, J=7). Example 10 (1S,2R,5S)-(+)-Menthyl-(4S,5R)-N-(tert-butoxycarbonyl)-4-phenyloxazolidin-2-one-5-carboxylate To a stirred solution of 1.91 g (5.52 mmol) of (1 S,2R,5S)(+)-menthyl-(4S,5R)-4-phenyl-oxazolidin-3-one-5-carboxylate in 20 ml of anhydrous tetrahydrofuran at -40 °C was added 3.8 ml (6.07 mmol) of 1.6 M butyllithium solution in hexane. After stirring for 10 min at -40 °C, a solution of 1.81 g (8.28 mmol) of di(tert-butoxy)-dicarbonate in 5 ml of tetrahydrofuran was added and the reaction mixture was allowed to warm to room temperature over 15 min. After dilution with 50 ml of methylene chloride and washing with 2% aqueous hydrochloric acid until pH=5, the organic phase is dried over magnesium sulfate and evaporated under reduced pressure. After chromatography of the crude product on silica gel (particle size 15-40 pm) (eluent=cyclohexane:ethyl acetate; volume ratio=5:1), 2.12 g (yield=86%) of (1S,2R,5S)-(+)-menthyl-(4S,5R)-N-(tert-butoxycarbonyl)-4-phenyloxazolidin-2-one-5-carboxylate of formula (P10) is obtained as a colorless syrup. Characteristic properties of the obtained compound:1H-NMR spectrum (400 MHz; CHCl3-d) (chemical shifts δ, ppm; coupling constants J, Hz): 7.45-7.26 (5H, m); 5.19 (1H, d, J=3.7); 4.86 (1H, dt, J=10.9 and 4.5); 4.66 (1H, d, J=3.7); 2.05 (1H, m); I, 79 (1H, m); 1.73 (1H, m); 1.62-1.24 (3H, m); 1.33 (9H, s); 1.11 (2H, m); 0.94 (3H, d, J=6.5) and (1H, m); 0.89 (3H, d, J=7); 0.77 (3H, d, J=7). Example II (1S,2R,5S)-(+)-Menthyl-(4S,5R)-3-N-benzoyl-4-phenyloxazolidin-3-one-5-carboxylate Under an inert atmosphere, to a solution of 500 mg (1.45 mmol) of (1S,2R,5S)-(+)-menthyl-(4S,5R)-4-phenyl-oxazolidin-3-one-5-carboxylate and 176 mg (1.16 mmol) of 4-pyrrolidino-pyridine in 7 ml of anhydrous methylene chloride at room temperature, 0.25 ml (2.17 mmol) of benzoyl chloride was added with stirring. After stirring for 3 hours at 50 °C, the reaction mixture was cooled to room temperature and diluted with 20 ml of methylene chloride. The organic phase was washed with 10 ml of saturated aqueous sodium chloride solution, dried over magnesium sulfate and evaporated under reduced pressure. After chromatography of the crude product on silica gel (particle size 15-40 pm) (eluent=cyclohexane:ethyl acetate; volume ratio=5:1), 300 mg (yield=46%) of the compound of formula (P11) was obtained as a colorless syrup. Characteristic properties of the obtained compound:1H-NMR spectrum (400 MHz; CHCl3-d) (chemical shifts δ, ppm; coupling constants J, Hz): 8.16 (2H, d, J=7.1); 7.68 (1H, t); 7.53 (4H, m); 7.43 (3H, m); 5.57 (1H, d, J=4.4); 4.90 (1H, dt, J=10.9 and 4.4); 4.85 (1H, d, J=4.3); 2.07 (1H, m); 1.80 (2H, m); 1.72 (2H, m); 1.47 (3H, m); 1.09 (2H, m); 0.95 (3H, d, J=6.5) 0.88 (3H, d, J=7); 0.78 (3H, d, J=7). Example 12 (4S,5R)-3-N-Benzoyl-4-phenyl-oxazolidin-3-one-5-carboxylic acid To a solution of 120 mg (0.266 mmol) (1S,2R,5S)-(+)-menthyl(4S,5R)-3-N-benzoyl-4-phenyl-oxazolidin-3-one-5-carboxylate in 2 ml of methanol, stirred at room temperature, was added a solution of 75 mg (0.543 mmol) of potassium carbonate in 1 ml of water. After stirring for thirty minutes, the reaction mixture was diluted with 10 ml of water and the aqueous phase was washed with 5 ml of methylene dichloride. After acidification with aqueous 1 M hydrochloric acid to pH=4, the resulting aqueous phase was extracted with ethyl acetate (3*10 ml). The combined organic phases were washed with 5 ml of saturated aqueous sodium chloride solution, dried over magnesium sulfate and evaporated under reduced pressure. In this way, 40 mg (yield=52%) of (4S,5R)-3-N-benzoyl-4-phenyl10 of formula (P12) were obtained as a colorless powder. HU 225 507 Β1 oxazolidin-3-one-5-carboxylic acid is obtained, the characteristic properties of which are as follows: 1H-NMR spectrum (400 MHz; DMSO-d6) (chemical shifts δ, ppm; coupling constants J, Hz): 12.98 (1H, sz s); 7.95 (2H, d, >7.1); 7.63 (1H, t, >7.4); 7.50 (2H, t, J=7.5); 7.42 (2H, m); 7.37 (3H, m); 4.90 (1H, d, J=5); 4.77 (1H, d, >5). Example 13 (4S,5R)-4-Phenyl-oxazolidin-3-one-5-carboxylic acid To a solution of 300 mg (0.867 mmol) of (4S,5R)-3-N-benzoyl-4-phenyloxazolidin-3-one-5-carboxylic acid in 3 ml of methanol and then 0.5 ml of water in 6.5 ml of pyridine, stirred under an inert atmosphere at 0 °C, was rapidly added a solution of 360 mg (8.67 mmol) of sodium hydroxide, 3 ml of methanol and 0.5 ml of water in 6.5 ml of pyridine. After stirring for twenty minutes at 0 °C, the reaction mixture was diluted with 30 ml of water and washed with 30 ml of methylene chloride. After acidification to pH=1, the remaining aqueous phase was extracted with ethyl acetate (3*20 ml) and the resulting organic phases were dried over magnesium sulfate and evaporated under reduced pressure. In this way, 86 mg (yield=53%) of (4S,5R)-4-phenyl-oxazolidin-3-one-5-carboxylic acid of formula (P13) are obtained in the form of a yellow syrup, the characteristic properties of which are as follows: 1H-NMR spectrum (400 MHz; DMSO-d6) (chemical shifts δ, ppm; coupling constants J, Hz): 13.33 (1H, sz s); 8.46 (1H, s); 7.38 (5H, m); 4.89 (1H, d, J=5); 4.75 (1H, d, >5). II. Derivatives of baccatin III Example 14 7-O-(Triethylsilyl)-10-deacetylbaccatin III At room temperature and in an inert atmosphere, to a solution of 10 g (18.3 mmol) of 10-deacetylbaccatin III and 8.17 g (54.9 mmol) of 4-pyrrolidinopyridine in 500 ml of anhydrous methylene chloride was added 6.2 ml (36.6 mmol) of (triethylsilyl) chloride with stirring. After stirring for three hours at room temperature, 10 g of crushed ice was added and the reaction mixture was stirred vigorously for 10 minutes. The resulting organic phase was washed with water (200 ml), dried over magnesium sulfate and evaporated under reduced pressure. After treatment of the crude product obtained with a minimum amount of ethyl acetate, 11.2 g (yield=92.3%) of 7-O-(triethylsilyl)-10-deacetylbaccatin III of formula (P14) were obtained. The compound thus obtained exhibits the following characteristic properties: 1H-NMR spectrum (400 MHz; CHCl3-d) (chemical shifts δ, ppm; coupling constants J, Hz): 8.10 (2H, d, J=7.4); 7.60 (1H, t, J=7.5); 7.47 (2H, t, J=7.6); 5.60 (1H, d, J=7); 5.17 (1H, d, >1.9); 4.96 (1H, d, >8); 4.86 (1H, m); 4.41 (1H, dd, >10.6 and 6.6); 4.31 and 4.16 (2H, 2d, >8.4); 4.26 (1H, d J=1.9); 3.95 (1H, d, >6.9); 2.48 (1H, ddd, J=14.5, 9.7 and 6.7); 2.29 (3H, s); 2.27 (2H, m); 2.08 (3H, s); 1.90 (1H, m); 1.73 (3H, s); 1.62 (1H, s); 1.08 (6H, s); 0.94 (9H, t, J=8) 0.56 (6H, m). Example 15 7-O-(Triethylgermanyl)-10-deacetylbaccatin III At room temperature and in an inert atmosphere To a solution of 100 mg (0.183 mmol) of 10-deacetylbaccatin III and 41 mg (0.275 mmol) of 4-pyrrolidinopyridine in 4 ml of anhydrous methylene chloride was added 80 μΙ (0.476 mmol) of (triethylgermanyl) chloride over ten minutes with stirring, and the reaction mixture was stirred at 50 °C for thirteen hours. After cooling the reaction mixture and diluting it with 15 ml of methylene chloride, 1 g of crushed ice was added and the reaction mixture was stirred vigorously for 10 minutes. The resulting organic phase was washed with saturated aqueous sodium bicarbonate solution (5 ml), saturated aqueous sodium chloride solution (5 ml), dried over magnesium sulfate, and concentrated under reduced pressure. After chromatography of the crude product on silica gel (particle size 15-40 pm) (eluent=cyclohexane:ethyl acetate; volume ratio=25:75), 67 mg of 7-O-(triethylgermanyl)-10-deacetylbaccatin III of formula (P15) are obtained as a colorless syrup. The characteristic properties obtained in this way are: 1H-NMR spectrum (400 MHz; CHCl3-d) (chemical shifts δ, ppm; coupling constants J, Hz): 8.09 (2H, d, >7.1); 7.60 (1H, t, J=7.4); 7.48 (2H, t, J=7.6); 5.63 (1H, d, J=7); 5.24 (1H, s); 4.99 (1H, d, >8); 4.78 (1H, t); 4.32 (1H, d, >8.3); 4.28 (1H, m); 4.17 (2H, m); 3.97 (1H, d, >7); 2.59 (1H, m); 2.30 (3H, s); 2.24 (1H, m); 2.10 (1H, m); 2.03 (3H, s); 1.82 (1H, m); 1.73 (3H, s); 1.11 (9H, s); 1.0 (6H, t, >7.7). Example 16 7-O-[(2,2,2-Trichloro-tert-butoxy)-carbonyl]-10-deacetyl-baccatin III at °C and inert atmosphere 5 g (9.19 mmol) To a solution of 10-deacetylbaccatin III and 1.1 ml of anhydrous pyridine in 250 ml of anhydrous methylene chloride, 3.3 g (13.8 mmol) of [(2,2,2-trichloro-tert-butoxy)-carbonyl]-chloride were added with stirring over a period of two hours. After a further 30 minutes of reaction time and cooling to room temperature, the organic phase was washed with 2% aqueous hydrochloric acid (30 ml) and then with osmotically purified water (2*100 ml), dried over magnesium sulfate and concentrated under reduced pressure (yield=50%). After chromatography of the crude product on silica gel (particle size 15-40 pm) (eluent=cyclohexane:ethyl acetate; volume ratio=60:40), 7-0-((2,2,2-trichloro-tert-butoxy)-carbonyl]-10-deacetyl-baccatin III of formula (P16) is obtained as a colorless powder. The characteristic properties of the compound obtained in this way are: 1H-NMR spectrum (400 MHz; CHCl3-d) (chemical shifts δ, ppm; coupling constants J, Hz): 8.10 (2H, d, >7); 7.62 (1H, t, J=7.4); 7.49 (2H, t, J=7.6); 5.65 (1H, d, >6.9); 5.44 (1H, dd, >10.8 and 7.3); 5.39 (1H, d); 4.98 (1H, d, >7.5); 4.89 (1H, m); 4.35 and 4.20 (2H, 2d, >8.4); 4.10 (1H, d, >7); 4.01 (1H, d, >8); 2.64 (1H, m); 2.31 (1H, m); 2.29 (1H, m); 2.11 (3H, d); 2.05 (2H, m); 1.89 (3H, s); 1.09 (3H, s); 1.07 (3H, s). HU 225 507 B1 Example 17 7-O-(Triethylsilyl)-baccatin III At room temperature and in an inert atmosphere, 1 g (1.5 mmol) of 7-O-(triethylsilyl)-10-deacetylbaccatin III and To a solution of 1.25 ml (15 mmol) of anhydrous pyridine in 15 ml of methylene chloride, 0.54 ml (7.5 mmol) of acetyl chloride was added with stirring over 10 minutes. After a reaction time of two hours at room temperature and thin-layer chromatography monitoring, 1 g of crushed ice was added and the reaction mixture was stirred vigorously for 10 minutes. The resulting organic phase was washed with 2*10 ml of water, dried with magnesium sulfate and evaporated under reduced pressure. After purification by chromatography on silica gel (particle size 15-40 pm) (eluent=cyclohexane:ethyl acetate; volume ratio: 60:40), 0.756 g (yield=70%) of 7-O-(triethylsilyl)-baccatin III of formula (P17) was obtained as a colorless powder. Characteristic properties of the obtained compound:1H-NMR spectrum (400 MHz; CHCl3-d) (chemical shifts δ, ppm; coupling constants J, Hz): 8.11 (2H, d, J=7.1); 7.6 (1H, t, J=7.4); 7.48 (2H, t, J=7.7); 6.46 (1H, s); 5.63 (1H, d, J=7); 4.96 (1H, d, J=8.1); 4.83 (1H, m); 4.49 (1H, dd, J=10.4 and 6.7); 4.31 and 4.15 (2H, 2d, J=8.3); 3.88 (1H, d, J=7); 2.53 (1H, m); 2.29 (3H, s); 2.27 (2H, m); 2.19 (3H, d, J=0.8); 2.18 (3H, s); 2.12 (1H, d); 1.88 (1H, m); 1.68 (3H, s); 1.65 (1H, s); 1.2 (3H, s); 1.04 (3H, s); 0.92 (9H, t); 0.59 (6H, m). Example 18 7-O-[(2,2,2-Trichloro-tert-butoxy)-carbonyl]-baccatin III At room temperature and in an inert atmosphere, 50 µl (0.695 mmol) of acetyl chloride is added to a solution of 1 g (1.5 mmol) of 7-O-[(2,2,2-trichloro-tert-butoxy)-carbonyl]-10-deacetyl-baccatin III and 127.5 mg (1.04 mmol) of 4-(dimethylamino)-pyridine in 2.5 ml of anhydrous methylene dichloride while stirring. After a reaction time of one hour at room temperature, the organic phase is washed with 2% aqueous hydrochloric acid until pH=6, dried with magnesium sulfate and evaporated under reduced pressure. After purification of the resulting residue by chromatography on silica gel (particle size 15-40 pm) (eluent=cyclohexane:ethyl acetate; volume ratio=6:4), 0.23 g (yield=83%) of 7-O[(2,2,2-trichloro-tert-butoxy)-carbonyl]-baccatin III of formula (P18) was obtained as a solid product. Characteristic properties of the obtained compound:1H-NMR spectrum (400 MHz; CHCl3-d) (chemical shifts δ, ppm; coupling constants J, Hz): 8.11 (2H, d, J=7.1); 7.62 (1H, t, J=7.4); 7.49 (2H, t, J=7.6); 6.39 (1H, s); 5.64 (1H, d, J=6.9); 5.61 (1H, dd, J=10.7 and 7.2); 4.99 (1H, d, J=8.2); 4.87 (1H, m); 4.33 and 4.16 (2H, 2d, J=8.4); 4.02 (1H, d, J=6.9); 2.64 (1H, ddd, J=14.4, 9.5 and 7.2); 2.30 (3H, s) and (2H, m); 2.17 (3H, s); 2.13 (3H, d, J=0.8); 2.04 (1H, m); 1.83 (3H, s); 1.63 (1H,s); 1.14 (3H, s); 1.09 (3H, s). Example 19 7-O-(Phenoxyacetyl)-10-deacetylbaccatin III At room temperature and in an inert atmosphere To a stirred solution of 1.03 g (1.88 mmol) of 10-deacetylbaccatin III and 0.6 ml (7.5 mmol) of anhydrous pyridine in 100 ml of anhydrous methylene chloride was added 1.05 ml (7.5 mmol) of (phenoxyacetyl) chloride over ten minutes. After a further 30 minutes of reaction at room temperature and monitoring by thin layer chromatography, the reaction mixture was washed with 2% aqueous hydrochloric acid until pH=2, then with osmotically purified water (2*50 ml), dried with magnesium sulfate and concentrated under reduced pressure (yield=70.5%). After chromatography of the crude product on silica gel (particle size 15-40 pm) (eluent=cyclohexane:ethyl acetate; volume ratio=60:40), 7-O-(phenoxyacetyl)-10-deacetylbaccatin III of formula (P19) is obtained as a colorless powder. Characteristic properties of the obtained compound:1H-NMR spectrum (400 MHz; CHCl3-d) (chemical shifts δ, ppm; coupling constants J, Hz): 8.09 (2H, d, J=7.3); 7.61 (1H, t, J=7.4); 7.48 (2H, t, J=7.6); 7.31 (2H, t, J=7.7); 6.99 (3H, m); 6.42 (1H, s); 5.61 (1H, d, J=7); 4.97 (1H, d, J=7.8); 4.86 (3H, m); 4.44 (1H, dd, J=10.6 and 6.8); 4.30 and 4.15 (2H, 2d, J=8.4); 3.86 (1H, d, J=7); 2.56 (1H, m); 2.27 (2H, s); 2.27 (2H, m); 2.05 (3H, s); 1.86 (1H, m); 1.68 (3H, s); 1.01 (3H, s); 0.98 (3H, s). Example 20 7,10-O-bis(Phenoxyacetyl)-10-deacetylbaccatin III At room temperature and in an inert atmosphere To a stirred solution of 500 mg (0.92 mmol) of 10-deacetylbaccatin III and 0.6 ml (7.36 mmol) of anhydrous pyridine in 50 ml of anhydrous methylene chloride was added 0.5 ml (3.68 mmol) of (phenoxyacetyl) chloride over ten minutes. After a further 6 hours of reaction at room temperature and thin layer chromatography, the organic phase was washed with 2% aqueous hydrochloric acid until pH=2, then with osmotically purified water (2*20 ml), dried with magnesium sulfate and concentrated under reduced pressure. After chromatographic purification of the crude product on silica gel (particle size 15-40 pm) (eluent=cyclohexane:ethyl acetate; volume ratio=60:40), 0.55 g (yield=74%) of 7,10-Ob / 's(phenoxyacetyl)-10-deacetylbaccatin III of formula (P20) is obtained as a colorless powder. Characteristic properties of the obtained compound:1H-NMR spectrum (400 MHz; CHCl3-d) (chemical shifts δ, ppm; coupling constants J, Hz): 8.09 (2H, d, J=7.1); 7.61 (1H, t, J=7.4); 7.48 (2H, t, J=7.6); 7,29 (2H, t, J=6,8); 7,22 (2H, t, J=7,5); 6,96 (4H, m); 6,84 (2H, d, J=7,9); 6,42 (1H, s); 5,69 (1H, dd, J=10,5 es 7,1); 5,60 (1H, d, J=6,9); 4,96 (1H, d, J=8,2); 4,84 (1H, t, J=7,4); 4,8 (2H, s); 4,8 (2H, s); 4,65 es 4,41 (2H, 2d, J=15,8); 4,32 es 4,14 (2H, 2d, J=8,4); 3,98 (1H, d, J=6,8); 2,65 (1H, m); 2,28 (3H, s); 2,26 (2H, m); 2,09 (3H, s); 1,80 (3H, s) es (1H, m); 0.98 (6H, s). 21. példa 7-O-(Fenoxi-acetil)-baccatin III is often used at the same time. 1,11 g (1,64 mmol) 7-O-(fenoxi-acetil)-10-dezace12 HU 225 507 Β1 til-baccatin III was added with stirring to a solution of 40 ml of anhydrous pyridine with 0.233 ml (3.27 mmol) of acetyl chloride over 10 minutes. After a reaction time of sixteen hours at room temperature and monitoring by thin layer chromatography, the reaction mixture was diluted with 50 ml of osmotic water and the aqueous phase was extracted with ethyl acetate (2*30 ml). The combined organic phases were washed with water (2*20 ml), dried with magnesium sulfate and evaporated under reduced pressure (yield: 84.5%). After chromatography on silica gel (particle size 15-40 μηη), (eluent=cyclohexane:ethyl acetate; volume ratio: 60:40), crystalline 7-O-(phenoxyacetyl)-baccatin III of formula (P21) is obtained. Characteristic properties of the obtained compound:1H-NMR spectrum (400 MHz; CHCl3-d) (chemical shifts δ, ppm; coupling constants J, Hz): 8.10 (2H, d, J=7.1); 7.61 (1H, t, J=7.4); 7.48 (2H, t, J=7.7); 7.27 (2H, t, J=8); 6.95 (3H, m); 6.26 (1H, s); 5.71 (1H, dd, J=10.4 and 7.2); 5.62 (1H, d, J=6.9); 4.96 (1H, d, J=8.3); 4.80 (1H, m); 4.81 and 4.53 (2H, 2d, J=16); 4.32 and 4.14 (2H, 2d, J=8.5); 4.0 (1H, d, J=6.8); 2.64 (1H, m); 2.28 (3H, s); 2.24 (1H, d, J=5); 2.16 (3H, s); 2.09 (3H, d, J=0.7); 1.81 (1H, m) 1.78 (3H, s); 1.13 (3H,s); 1.08 (3H, s). Example 22 7,10-O-[(1,1,3,3-Tetraisopropyl)-1,3-disiloxanediyl]-10-desacetylbaccatin III To a stirred solution of 500 mg (0.93 mmol) of 10-deacetylbaccatin III in 20 mL of tetrahydrofuran at -40 °C and under an inert atmosphere, add over ten minutes 1.28 ml (2.05 mmol) of butyllithium in 1.6 M hexane solution. After stirring for five minutes, 350 μΙ (1.12 mmol) of 1,3-dichloro-(1,1,3,3-tetraisopropyl)-1,3-disiloxane are added and the reaction mixture is allowed to warm to room temperature over twenty minutes. After stirring at room temperature for one hour, 225 mg (205 mmol) are added 4-(dimethylamino)pyridine, and the reaction mixture is stirred for another hour. After adding 20 ml of saturated aqueous sodium chloride solution, the medium is extracted with methylene chloride (3*30 ml). The combined organic phases are washed with saturated aqueous sodium chloride solution (20 ml), dried over magnesium sulfate and evaporated under reduced pressure. After chromatographic purification on silica gel (particle size 15-40 pm) (eluent=cyclohexane:ethyl acetate; volume ratio=60:40), 480 mg (yield=65%) of amorphous 7,10-O-[(1,1,3,3-tetraisopropyl)-1,3-disiloxanediyl]-10-deacetylbaccatin III of formula (P22) is obtained. Characteristic properties of the obtained compound:1H-NMR spectrum (400 MHz; CHCl3-d) (chemical shifts δ, ppm; coupling constants J, Hz): 8.10 (2H, d, J=7.2); 7.60 (1H, t, J=7.4); 7.47 (2H, t, J=7.6); 5.60 (1H, s); 5.59 (1H, d); 4.97 (1H, d, J=7.9); 4.87 (1H, m); 4.68 (1H, dd, J=10.4 and 6.9); 4.30 and 4.17 (2H, 2d, J=8.5); 3.92 (1H, d, J=7.1); 2.49 (1H, m); 2.28 (3H, s); 2,28 (3H, s); 2,27 (1H, m); 2,04 (3H, s); 1,91 (1H, m); 1,67 (3H, s); 1,55 (1H, s); 1.32-0.85 (34H, m). 23. példa 13-0-{[(4S, 5R)-2,4-Difenil-4,5-dihidrooxazol-5il]-karbonil}-7-O-(trietil-szilil)-baccatin III To a solution of 2.67 g (10 mmol) of (4S,5R)-2,4-diphenyl-4,5-dihydrooxazole-5-carboxylic acid in 55 ml of anhydrous toluene was added 2.06 g (10 mmol) of Ν,Ν-dicyclohexylcarbodiimide with stirring at room temperature and under an inert atmosphere. After stirring for five minutes, 3.5 g (5 mmol) of 7-O-(triethylsilyl)baccatin III and 0.61 g (5 mmol) of 4-(dimethylamino)pyridine were added and the reaction mixture was heated at 70 °C for 1 hour. After cooling to room temperature and removal of insoluble by-products by filtration, the organic phase was evaporated under reduced pressure. After chromatography of the crude product on silica gel (particle size 15-25 pm) (eluent=cyclohexane:ethyl acetate; volume ratio=90:10), 4.62 g (yield=97%) of crystalline 13-O-{[(4S,5R)-2,4-diphenyl-4,5-dihydrooxazol-5-yl]-carbonyl}-7-O-(triethylsilyl)-baccatin III of formula (P23) was obtained. The characteristic properties of the compound obtained in this way are: 1H-NMR-spektrum (400 MHz; CHCI3-d) (kémiai eltolódások δ, ppm; kapcsolási állandók J, Hz): 8.23 ​​(2H, d, J=7.2); 8,07 (2H, d, J=7,3); 7,63 (1H, t, J=7,4); 7,58 (1H, t, J=7,4); 7,49 (4H, m); 7,38 (5H, m); 6,42 (1H, s); 6,18 (1H, t, J=8,2); 5,68 (1H, d, J=7,1); 5,60 (1H, d, J=6,5); 4,95 (2H, d); 4,50 (1H, dd, J=10,5 es 6,7); 4,29 (1H, d, J=8,4); 4,14 (1H, d, J=8,4); 3,83 (1H, d, J=7,1); 2,55 (1H, m); 2,37 (1H, dd, J=15,3 es 9,3); 2,26 (1H, dd, J=15,3 es 8,6); 2,16 (3H, s); 2,07 (3H, s); 1,99 (3H, s); 1,89 (1H, m); 1,72 (1H, s); 1,69 (3H, s); 1,23 (3H, s); 1,19 (3H,s); 0.92 (9H, t, J=8); 0.57 (6H, m). 24. példa 13-O-{[(4S,5R)-2,4-Difenil-4,5-dihidrooxazol-5il]-karbonil}-7-O-(fenoxi-acetil)-baccatin III To a solution of 490 mg (1.83 mmol) of (4S,5R)-2,4-diphenyl-4,5-dihydrooxazole-5-carboxylic acid in 10 ml of anhydrous toluene, 380 mg (1.84 mmol) of Ν,Ν-dicyclohexylcarbodiimide were added with stirring at room temperature and under an inert atmosphere. After stirring for five minutes, 660 mg (0.92 mmol) of 7-O-(phenoxyacetyl)baccatin III and 112 mg (0.92 mmol) of 4-(dimethylamino)pyridine were added, and the reaction mixture was heated at 70 °C for 2 h. After cooling to room temperature and removing insoluble by-products by filtration, the organic phase was concentrated under reduced pressure. After chromatography of the crude product on silica gel (particle size 15-40 pm) (eluent=cyclohexane:ethyl acetate; volume ratio: 99:1), 800 mg (yield=90%) of crystalline 13-O-{[(4S,5R)-2,4-diphenyl-4,5-dihydrooxazol-5-yl]-carbonyl}-7-O-(phenoxyacetyl)-baccatin III of formula (P24) was obtained. The characteristic properties of the compound thus obtained:1H-NMR spectrum (400 MHz; CHCl3-d) (chemical shifts δ, ppm; coupling constants J, Hz): 8.18 (2H, d, J=7); 8.07 (2H, d, J=7.3); 7.63 (1H, t, J=7.4); HU 225 507 B1 7.59-7.32 (1 OH, m); 7.28 (2H, t, J=7.5); 6.94 (3H, m); 6.23 (1H, s) and (1H, m); 5.70 (1H, dd, J=10.4 and 7.1); 5.67 (1H, d, J=7.3); 5.58 (1H, d, J=7); 4.93 (2H, d); 4.79 and 4.53 (2H, 2d, J=15.9); 4.30 and 4.13 (2H, 2d J=8.5); 3.97 (1H, d, J=6.9); 2.67 (1H, m); 2.38 (1H, dd, J=15.2 and 9.3); 2.26 (1H, dd, J=15.2 and 8.4); 2.15 (3H, s); 2.02 (3H, s); 1.95 (3H, s) and (1H, m); 1.80 (3H, s); 1.74 (1H, s); 1.25 (3H, s); 1.17 (3H, s). Example 25 13-O-{[(4S,5R)-2,4-Diphenyl-4,5-dihydrooxazol-5-yl]-carbonyl}-7-O-[(2,2,2-trichloro-tert-butoxy)-carbonyl]-baccatin III To a solution of (4S,5R)-2,4-diphenyl-4,5-dihydrooxazol-5-carboxylic acid in 3 ml of anhydrous toluene, 27 mg (0.13 mmol) of N,N-dicyclohexylcarbodiimide were added under stirring at room temperature and in an inert atmosphere. After stirring for five minutes, 51 mg (0.065 mmol) of 7-O-[(2,2,2-trichloro-tert-butoxy)carbonyl]baccatin III and 8 mg (0.065 mmol) of 4-(dimethylamino)pyridine were added, and the reaction mixture was heated at 70°C for one hour. After cooling to room temperature and removing insoluble by-products by filtration, the organic phase is evaporated under reduced pressure and the crude product is purified by chromatography on silica gel (particle size 15-40 pm; eluent=cyclohexane:ethyl acetate, volume ratio=9:1). In this way, 0.99 g (yield=67%) of 13-O-{[(4S,5R)-2,4-diphenyl-4,5-dihydrooxazol-5-yl]-carbonyl}-7-O-[(2,2,2-trichlorotert-butoxy)-carbonyl]-baccatin III of formula (P25) is obtained as a white, solid product, the characteristic properties of which are as follows: 1H-NMR spectrum (400 MHz; CHCl3-d) (chemical shifts δ, ppm; coupling constants J, Hz): 8.18 (2H, d, J=7.2); 8.07 (2H, d, J=7.3); 7.65 (1H, t, J=7.4); 7.59 (1H, tJ=7.3); 7.52 (4H, m); 7.39 (5H, m); 6.35 (1H, s); 6.24 (1H, t, J=8.4); 5.68 (1H, d, J=7.1); 5.59 (1H, d, J=7) and (1H, dd); 4.95 (1H, d); 4.94 (1H, d, J=7); 4.31 and 4.15 (2H, 2d J=8.4); 3.97 (1H, d, J=6.9); 2.64 (1H, m); 2.37 (1H, dd, J=15.1 and 6); 2.27 (1H, dd, J=15.2 and 8.5); 2.16 (3H, s); 2.01 (3H, s); 1.98 (3H, s) 1.83 (3H, s); 1.72 (1H, s); 1.25 (3H, s); 1.18 (3H,s). Example 26 13-O-{[(4S,5R)-2,4-Diphenyl-4,5-dihydrooxazol-5-yl]-carbonyl}-7,10-O-[(1,1,3,3-tetraisopropyl)-1,3-disiloxanediyl]-10-deacetylbaccatin III To a solution of 4 mg (0.015 mmol) of (4S,5R)-2,4-diphenyl-4,5-dihydrooxazol-5-carboxylic acid in 0.5 ml of anhydrous toluene, 7 mg (0.06 mmol) of N,N-dicyclohexylcarbodiimide were added under stirring at room temperature and in an inert atmosphere. After stirring for five minutes, 5 mg (0.0065 mmol) of 7,10-β-[(1,1,3,3-tetraisopropyl)-1,3-disiloxanediyl]-10-deacetylbaccatin III and a solution of 1 mg (0.0078 mmol) of 4-(dimethylamino)pyridine in 1 ml of anhydrous toluene were added, and the reaction mixture was heated at 50 °C for twenty minutes. After cooling to room temperature, the organic phase was diluted with 100 ml of methylene chloride, washed with 2 ml of aqueous sodium chloride solution, dried over magnesium sulfate, and concentrated under reduced pressure. After chromatography of the crude product on silica gel (particle size 15-25 pm) (eluent=cyclohexane:ethyl acetate; volume ratio=7:3), 6 mg (yield=90%) of amorphous 13-0-{[(4S,5R)-2,4-diphenyl-4,5-dihydrooxazol-5-yl]-carbonyl}-7,10-[(1,1,3,3-tetraisopropyl)-1,3-disiloxanediyl]-10-deacetylbaccatin III of formula (P26) is obtained, the characteristic properties of which are as follows:1H-NMR spectrum (400 MHz; CHCl3-d) (chemical shifts δ, ppm; coupling constants J, Hz): 8.21 (2H, d, J=7.2); 8.07 (2H, d, J=7.6); 7.63 (1H, t, J=7.5); 7.59 (1H, tJ=7.4); 7.50 (2H, t, J=7.4); 7.39 (5H, m); 6.26 (1H, t); 5.64 (1H, d, J=7); 5.59 (1H, d, J=6.9); 5.54 (1H, s); 4.93 (1H, d, J=6.8) and (1H, m); 4.68 (1H, dd); 4.28 and 4.16 (2H, 2d J=8); 3.84 (1H, d, J=7.3); 2.48 (1H, m); 2.35 and 2.25 (2H, 2dd); 2.02 (3H, s); 1.88 (3H, s) and (1H, m); 1.67 (3H, s); 1.63 (1H, s); 1.30-0.90 (34H, m). Example 27 13-0-{[(4S, 5R)-3-N-Benzoyl-4-phenyl-oxazolidin-3-one-5-yl]-carbonyl}-7-O-(triethylsilyl)-baccatin III To a solution of 40 mg (0.137 mmol) of (4S,5R)-3-N-benzoyl-4-phenyl-oxazolidin-3-one-5-carboxylic acid in 2 ml of anhydrous toluene, 28 mg (0.136 mmol) of Ν,Ν-dicyclohexylcarbodiimide were added under stirring at room temperature and in an inert atmosphere. After stirring for five minutes, 30 mg (0.043 mmol) of 7-O-(triethylsilyl)baccatin III and 8 mg (0.066 mmol) of 4-(dimethylamino)pyridine were added and the reaction mixture was heated at 60°C for 13 hours. After cooling to room temperature, the reaction mixture was diluted with 100 ml of methylene chloride, and the organic phase was washed with 5 ml of aqueous sodium chloride solution, dried over magnesium sulfate, and concentrated under reduced pressure. After chromatography on silica gel (particle size 15-40 pm) (eluent=cyclohexane:ethyl acetate; volume ratio=2:1), 13 mg (yield=31%) of amorphous 13-O-{[(4S,5R)3-N-benzoyl-4-phenyl-oxazolidin-3-on-5-yl]-carbonyl}-7-O(triethylsilyl)-baccatin III of formula (P27) was obtained, the characteristic properties of which are as follows: 1H-NMR spectrum (400 MHz; CHCl3-d) (chemical shifts δ, ppm; coupling constants J, Hz): 8.06 (2H, d, J=7.3); 7.72 (2H, d, J=7); 7.63 (1H, t, J=7.4); 7.58 (1H, t J=7.4); 7.54-7.44 (8H, m); 7.40 (1H, t); 6.44 (1H, s); 6.33 (1H, t); 5.73 (1H, d, J=5.7); 5.67 (1H, d, J=5.7); 5.54 (1H, s); 4.96 (1H, d, J=5.8); 4.88 (1H, d, J=8.3); 4.45 (1H, dd, J=10.4 and 6.6); 4.27 and 4.12 (2H, 2d J=8.3); 3.80 (1H, d, J=7); 2.50 (1H, m); 2.26 (2H, m); 2.19 (3H, s); 2.07 (3H, s); 1.98 (3H, s); 1.85 (1H, m) 1.76 (1H, s); 1.67 (3H, s); 1.24 (3H, s); 1.23 (3H, s); 0.91 (9H, t, J=7.9); 0.56 (6H, m). Example 28 13-0-{[(4S, 5R)-2,4-Diphenyl-4,5-dihydrooxazol-5-yl]-carbonyl}-7,10-O-b'\s(phenoxyacetyl)-10-deacetylbaccatin III mg (0.293 mmol) (4S,5R)-2,4-diphenyl-4,5-dihydrooxazol-5-carboxylic acid 3 ml anhydrous toluene prepared ol14 HU 225 507 To the Β1 data while stirring, at room temperature and in an inert atmosphere, 65 mg (0.315 mmol) of N,N-dicyclohexylcarbodiimide are added. After five minutes of stirring, 237 mg (0.293 mmol) of 7,10-Ob / s(phenoxyacetyl)-10-deacetylbaccatin III and 36 mg (0.295 mmol) of A solution of 4-(dimethylamino)pyridine in 3 ml of toluene was added, and the reaction mixture was heated at 60 °C for 1 hour. After cooling to room temperature and removing insoluble by-products by filtration, the organic phase was evaporated under reduced pressure, and the resulting crude product was purified by chromatography on silica gel (particle size 15-40 pm; eluent=cyclohexane:ethyl acetate, volume ratio: 1:1). In this way, 280 mg (yield=90%) of amorphous 13-O-{[(4S,5R)-2,4-diphenyl-4,5-dihydrooxazol-5-yl]-carbonyl}-7,10-O-[(phenoxyacetyl)-10-deacetylbaccatin III of formula (P28) are obtained, the characteristic properties of which are as follows: 1H-NMR spectrum (400 MHz; CHCl3-d) (chemical shifts δ, ppm; coupling constants J, Hz): 8.18 (2H, d, J=7); 8.06 (2H, d, J=7.1); 7.64 (1H, d, J=7.4); 7.58 (1H, t J=7.3); 7.51 (4H, m); 7.39 (5H, m); 7.25 (4H, m); 6.96 (4H, m); 6.85 (2H, d, J=8); 6.33 (1H, s); 6.19 (1H, T, J=9); 5.68 (1H, dd, J=10.5 and 7.1); 5.65 (1H, d, J=6.9); 5.59 (1H, d, J=7); 4.93 (2H, d, J=7.1); 4.79 (2H, s); 4.63 and 4.40 (2H, 2d, J=15, 9); 4.30 and 4.13 (2H, 2d J=8.4); 3.94 (1H, d, J=6.9); 2.68 (1H, m); 2.37 (1H, dd, J=15.3 and 9.3); 2.24 (1H, dd, J=15.3 and 8.7); 2.02 (3H, s); 1.95 (3H, s); 1.80 (3H, s) and (1H, m); 1.69 (1H, s); 1.12 (3H, s); 1.01 (3H,s). III. Semisynthesis Example 29 Production of Paclitaxel a) Starting from 13-O-{[(4S,5R)-2,4-Diphenyl-4,5-dihydrooxazol-5-yl]-carbonyl}-7-O-(triethylsilyl)-baccatin III, 0.6 L (0.6 mol) of 1 M aqueous hydrochloric acid solution was added to a solution of 13-O-{[(4S,5R)-2,4-diphenyl-4,5-dihydrooxazol-5-yl]-carbonyl}-7-O-(triethylsilyl)-baccatin III in 1.2 L of tetrahydrofuran and 1.2 L of methanol at room temperature, and the reaction mixture was stirred at room temperature for 4 hours and 30 minutes. After adding 3.5 liters of saturated sodium bicarbonate solution, the homogeneity of the solution is ensured by adding 6 liters of tetrahydrofuran and 6 liters of water, and the reaction mixture is stirred for a further 1 hour and 30 minutes. After adding 15 liters of ethyl acetate and 15 liters of osmotized water, the resulting aqueous phase is extracted with 15 liters of ethyl acetate. The organic phase is dried with magnesium sulfate, evaporated under reduced pressure, and the crude product is purified by chromatography on silica gel (particle size 15-40 pm) (eluent=cyclohexane:ethyl acetate; volume ratio: 1). In this way, 75 g (yield=95%) of taxol is obtained as a colorless crystalline product, the characteristic properties of which are in all respects consistent with the data reported in the literature. b) Starting from 13-O-{[(4S,5R)-2,4-Diphenyl-4,5-dihydrooxazol-5-yl]-carbonyl}-7-O-[(2,2,2-trichloro-tert-butoxy)-carbonyl]-baccatin III, 90 µl (0.09 mmol) of 1 M aqueous hydrochloric acid solution was added to a solution of 13-O-{[(4S,5R)-2,4-diphenyl-4,5-dihydrooxazol-5-yl]-carbonyl}-7-O-[(2,2,2-trichloro-tert-butoxy)-carbonyl]-baccatin III in 0.18 ml of tetrahydrofuran and 0.18 ml of methanol at room temperature, and the reaction mixture was stirred at room temperature for 8 hours. After adding 0.6 ml of saturated sodium bicarbonate solution, the solution is homogenized by adding 1 ml of tetrahydrofuran and 1 ml of water, and the reaction mixture is stirred for a further 1 hour and 30 minutes. After adding 2.5 ml of ethyl acetate and 2.5 ml of osmotized water, the resulting aqueous phase is extracted with 2.5 ml of ethyl acetate. The combined organic phases are dried over magnesium sulfate and evaporated under reduced pressure. In this way, 14 mg (yield=93%) of 7-O-[(2,2,2-trichloro-tert-butoxy)carbonyl]-taxol was obtained as crude product, which was used in the next reaction step without further purification. To a solution of 20 mg (0.0128 mmol) of 7-O-[(2,2,2-trichloro-tert-butoxy)-carbonyl]-taxol in 2 ml of ethyl acetate at room temperature, 30 µl (0.525 mmol) of acetic acid and 22.5 g (0.344 mmol) of zinc powder were added while stirring. After stirring the reaction mixture for 2 hours and 30 minutes at room temperature, it was checked by thin layer chromatography and diluted with 3 ml of ethyl acetate, the organic phase was washed with 1 ml of osmotized water, 1 ml of saturated sodium bicarbonate solution, then again with water, dried over magnesium sulfate, and evaporated under reduced pressure. After purification of the crude product by chromatography on silica gel (particle size 15-40 pm) (eluent=cyclohexane:ethyl acetate; volume ratio=6:4), 9.5 mg (yield=89%) of taxol was obtained as a crystalline product.

Claims

PATENT CLAIMS 1. Process for the preparation of side chain precursors of taxanes, characterized in that a cis-p-aryl-glycidate derivative of the general formula (I) - in which Ar represents an aryl group and R represents a hydrocarbon group, preferably a straight or branched chain alkyl or optionally a cycloalkyl group substituted with one or more alkyl groups - is stereospecifically converted in one step to introduce the pN-(alkylamido)- and the a-hydroxy group or their cyclic precursors by the Ritter reaction in such a way that either a) for the direct synthesis of a straight chain compound, a cis-p-aryl-glycidate derivative of the above-defined general formula (I) is reacted with a nitrile of the general formula R2-CN - in which R2 represents an aryl group - in the presence of a protonic acid and water to form a compound of the general formula (IIa) β-aryl-isose15 HU 225 507 β1 rine derivative - in which Ar, R and R2 are defined as above;or b) for the direct synthesis of a cyclic compound, a cis-p-aryl glycidate derivative of the general formula (I) as defined above is reacted with a nitrile of the general formula R'2-CN - in which R'2 is R2 as defined above or a lower alkyl or aryl group or a lower perhaloalkyl group, for example a trichloromethyl group - in the presence of a Lewis acid or a protonic acid, in an anhydrous medium to give an oxazoline of the general formula (IIb) - in which Ar, R and R'2 are as defined above.; 2. The process according to claim 1, characterized in that R is an optically pure enantiomer of a highly sterically chiral hydrocarbon group, preferably a cycloalkyl, especially a cyclohexyl, group substituted with one or more alkyl groups.

3. The process according to claim 2, characterized in that R is one of the enantiomers of the menthyl group, in particular (+)-menthyl group.

4. The process according to any one of claims 1-3, characterized in that the configuration of the ac's-p-phenylglycidate derivative is (2R,3R), and the compounds of general formula (IIa) and (IIb) obtained are of (2R,3S)-configuration.

5. The process according to any one of claims 1-4, characterized in that Ar and R2 are phenyl.

6. The process according to any one of claims 1-5, characterized in that in step a) the protonic acid is selected from sulfuric acid, perchloric acid or hydrogen [tetrafluoroborate], in step b) the Lewis acid is selected from boron trifluoride / acetic acid complex, boron trifluoride etherate, antimony pentachloride, tin tetrachloride, titanium tetrachloride, and in step b) the protonic acid is hydrogen [tetrafluoroborate].

7. The 1-6. A process according to any one of claims 1 to 3, characterized in that the β-aryl isoserine derivative of general formula (IIa) is converted into a compound of general formula (IIa) by protecting the hydroxy group with a suitable (GP) protecting group - in which Ar, R and R2 are as defined above, GP represents the hydroxy group suitable for the synthesis of taxanes, in particular alkoxyether, aralkoxyether, aryloxyether groups, or haloalkoxycarbonyl, for example methoxymethyl, 1-ethoxyethyl, benzyloxy, [ε-(trimethylsilyl)ethoxy]methyl, tetrahydropyranyl, β-alkoxycarbonyl (TrOC-), β-halogenated or alkylsilylated ethers or alkoxyacetyl, aryloxyacetyl, haloacetyl or formyl groups hydroxy protecting group.

8. The process according to any one of claims 1-6, characterized in that the β-aryl isoserine derivative of general formula (Ha) is converted into a new cyclic intermediate, an oxazolidinone of general formula (IIIa) - in which Ar and R are as defined above - a β-aryl isoserine derivative of general formula (Ha) according to claims 1-5. according to any one of claims 1 to 3, by reacting with a (haloalkoxy)carbonyl, in particular (2,2,2-trichloroethoxy)carbonyl (TrOC-) ester, followed by cyclization in the presence of a strong organic base, for example diazabicycloundecene (DBU), and optionally subsequently converting into an amide of the general formula (III'a) - in which Ar and R are as defined above and R"2 is as defined above, R'2 is an alkoxy or straight or branched chain alkyl group containing at least one unsaturation.

9. The process according to any one of claims 1-6, characterized in that the oxazoline of general formula (llb) is hydrolyzed in acidic medium to a β-aryl-isoserine derivative of general formula (IIIb) - in which Ar, R and R'2 are as defined above - which is optionally subsequently converted to the corresponding amide of general formula (lll'b) - in which Ar, R, R'2 and R'2 are as defined above.

10. A process according to any one of claims 1-9, characterized in that the cis-aryl glycidate of general formula (I) - in which Ar is as defined above and R is an optically pure enantiomer of a highly spherically hindered hydrocarbon group - is prepared by reacting an aldehyde of general formula Ar-CHO with a haloacetate of general formula X-CH2-CO2R - in which Ar, R is as defined above and X is a halogen, in particular chlorine or bromine atom.

11. The process according to any one of claims 1-9, characterized in that the compounds of the general formula (IIa), (II'a), (IIb), (IIIa), (IIIa'a), (IIIb) and (IIIb'b) defined above - in which R represents a hydrogen atom - are obtained by mild saponification.

12. Taxane side chain precursor compounds, which are compounds of the general formula (I), (IIa), (IIb), (II'a), (IIIb) and (III'b) - in which Ar, R2, R'2, R"2 and GP are as defined in any one of claims 1-3. and 5, and R is selected from one of the optically pure enantiomers of a bulky chiral hydrocarbon group.

13. Compounds according to claim 12, wherein R is any of the enantiomers of the menthyl group, in particular the (+)-menthyl group.

14. Compounds according to claim 12 or 13, wherein the cis-3-phenylglycidate of formula (I) has the (2R,3R) configuration and the compounds of formulae (IIa), (IIb), (IIIb) and (III'b) have the (2R,3S) configuration.

15. Taxane side chain precursor compounds selected from the group consisting of compounds of formula (IIIa) and (IIIa'a) - wherein Ar, R and R''2 are as defined above and R is hydrogen.

16. Compounds according to claim 15, which have the (2R,3S) configuration.

17. Process for the preparation of taxanes of general formula (IV) - in which B is a group of general formula (V), in which Ac is an acetyl group, Bz is a benzoyl group, HU 225 507 Β1 Me is a methyl group, R4 is an acetyl group or a protecting group for the GP1 hydroxy function, and R5 is a protecting group for the GP2 hydroxy function, and C is a side chain selected from groups of general formula (lla-1), (ll'a-1), (llb-1), (llla-1), (lll'a-1), (lllb-1) and (lll'b-1) (in which groups Ar, R2, R'2, R"2 and GP are as defined above) characterized in that a baccatin lll derivative of general formula (V) containing a hydroxy group at the C-13 position is prepared by a process according to claim 11 (lla), (ll'a), (llb), (llla), (lll'a), esterification with a compound of general formula (IIIb) or (III'b) - in which R represents a hydrogen atom.

18. The process according to claim 17, characterized in that the protecting groups GP1 and GP2 are independently conventional groups used in the semisynthesis of taxanes, for example trialkylsilyl or TrOC groups or a high-volume, straight or branched chain (haloalkoxy)carbonyl group containing at least one halogen atom, or acyl groups containing at least one oxygen atom on their α-carbon atom relative to the carbonyl group, a trialkylgermanyl group, or together they form a divalent group of general formula (c) - in which R7 and R8 are independently a high-volume alkyl group.

19. The process according to claim 17 or 18, characterized in that the acyl groups, which contain at least one oxygen atom on their α-carbon atom relative to the carbonyl group, are selected from i) alkoxyacetyl or aryloxyacetyl groups of general formula (a) - in which R6 represents a bulky alkyl, a cycloalkyl or aryl group - or ii) (arylidenedioxy)acetyl groups of general formula (b) - in which Ar" represents an arylidene group.

20. The method according to claim 19, characterized in that i) the alkyl group with a large volume of 1-6 carbon atoms is substituted with one or more halogen atoms, alkyl with a straight or branched chain having 1-6 carbon atoms, alkyl with a straight or branched chain having 1-6 carbon atoms, alkoxy with a straight or branched chain having 1-6 carbon atoms or cycloalkyl with a straight or branched chain having 3-6 carbon atoms, optionally substituted with one or more halogen atoms, alkyl with a straight or branched chain having 1-6 carbon atoms, alkyl with a straight or branched chain having 1-6 carbon atoms, alkoxy with a straight or branched chain having 1-6 carbon atoms or cycloalkyl with a straight or branched chain having 3-6 carbon atoms, preferably one or more halogen a cyclohexyl group substituted with a branched-chain alkyl group, for example a menthyl group, its racemate or enantiomers and mixtures thereof in any proportion, iii) the aryl group optionally comprising one or more halogen atoms, a group having 1 to 6 carbon atoms,a phenyl, naphthyl, anthryl or phenanthryl group substituted with a bulky group selected from the group consisting of straight or branched alkyl, straight or branched alkoxy having 1-6 carbon atoms or aryl, preferably phenyl, preferably optionally substituted with one or more of the aforementioned bulky groups in the ortho and ortho' positions relative to the ether bond, and iv) the arylidene group optionally substituted with one or more halogen atoms, a phenylene, naphthylene, anthrylene or phenanthrylene group substituted with a bulky group selected from the group consisting of straight or branched alkyl having 1-6 carbon atoms or aryl, preferably phenyl., 21. The process according to claim 17 or 18, wherein R4 is acetyl and GP2 is a trialkylsilyl, (2,2,2-trichloroethoxy)carbonyl, (2,2,2-tribromoethoxy)carbonyl, (1,2,2,2-tetrachloroethoxy)carbonyl, (2,2,2-trichlorotert-butoxy)carbonyl, (trichloromethoxy)carbonyl, phenoxyacetyl or trialkylgermanyl group.

22. The process according to claim 17 or 18, characterized in that R4 is GP1, and GP1 and GP2 are (2,2,2-trichloroethoxy)carbonyl or phenoxyacetyl, or together they form a group of general formula (c) - in which R7 and R8 are each isopropyl.

23. The process according to any one of claims 17-21, characterized in that C is a group of general formula (IIa-1) in which Ar and R2 are phenyl groups and R4 is acetyl group.

24. The process according to any one of claims 17-23, characterized in that the subsequent removal of the hydroxy-protecting group of the compounds of general formula (IV) and optionally simultaneously or separately opening the oxazoline ring of the group of general formula (llb-1) or (llla-1) yields the taxane derivatives of general formula (VI) - in which Ac, Bz, Me and R'2 are as defined in the preceding claims, R4 represents a hydrogen atom or an acetyl group, and R5 represents a hydrogen atom.

25. Taxane derivatives of the general formula (IV) - in which (C) and (B) are as defined in any one of claims 17-23 - with the exception of those compounds in which (C) is a group of the general formula (lla-1), (II'a-1), (llb-1), (lllb-1) or (lll'b-1), and GP1 and / or GP2 are independently conventional groups used in the semisynthesis of taxanes, for example a trialkylsilyl or TrOC group.

26. Baccatin lll derivatives useful for the semisynthesis of taxanes, which are compounds of general formula (V) - in which Ac is an acetyl group, Bz is a benzoyl group, Me is a methyl group, R4 is an acetyl group or a protecting group for the GP1 hydroxy function, R5 is a protecting group for the GP2 hydroxy function, and HU 225 507 Β1 GP1 and GP2 together form a divalent group of general formula (c) (in which R7 and R8 independently represent a bulky alkyl group) selected from 5. GP1 and GP2 independently represent bulky (haloalkoxy)carbonyl groups - acyl groups, with the exception of the TrOC group, whose carbon atom in the α-position relative to the carbonyl group carries at least one oxygen atom, trialkylgermanyl groups, or