Vitamin d precursors, process for their preparation and their intermediates

Description

Vitamin O precursors, process for their preparation, and their further intermediates The present invention relates to precursors which are excellently useful for the preparation of 19-nor-D-Vitamin analogues, and also to a process for their preparation and to intermediates useful therein. More particularly, the invention relates to precursors of the A-ring of the above-mentioned 18-nor-D-Vitamins, the A-ring of which can be characterized by the general formula (A), see e.g. Mazur et al., Tetrahedron Letters, 298? (1 S85)j The preparation of .bicyclo[3.1.0 Furthermore, 3-cyclopentane has also been used as a precursor for this process (W. Yong, M, V et al., Synlett, 9, 911-912 (1986)j. These procedures have the following disadvantages: - During the production of (-)-quinic acid, a radical deoxylation reaction takes place, which is difficult to control in large quantities, and the process requires the use of toxic tributyltin chloride. - The process starting from cyclohexanetriol goes through many steps (12 steps) and requires two enzymatic reactions. - The 3-cyclopentane starting material is not commercially available. It has to be prepared from cyclopentadiene by a hydroboration step, where the yield is low (30%). Furthermore, the cyclopropanation and the incorporation of the formyl group are difficult. In the process starting from 2,4-pentane-drone (step 10), the yield of step 1 for the preparation of the bis-epoxide intermediate is low. In addition, due to their low molecular weights, many intermediates are quite volatile and difficult to purify in large quantities. A number of 19-nor-A-ring precursors can be prepared from 3,5-dihydroxybenzoic acid derivatives or their 4-alkyl substituted homologues. These precursors can be prepared in large quantities by a process that is more efficient than those described so far. Accordingly, a first object of the invention is a process for the preparation of compounds of general formula (I) - in the formula - A means -CHjOH, ~CHj~OCöE', -CöR, -GSR” or etmilesopori; - R represents a hydrogen atom or a C<-C3 alkyl group; - R? represents a hydrogen atom, a C<~C?:alkyl group or a -(GH2k-OP group, - R2 represents a hydrogen atom or -GP; - R' represents a C1-C6alkyl group or a phenyl group; - R represents a hydrogen atom, a hydroxyl group, a C1-C3 alkyl group, a C1-C3 alkyl group. alkoxy, C1-C8alkyl or di(C1-C8alkyl)alkyl group; - P represents a hydrogen atom; a CvC6alkanoyl group; a benzene group in which the phenyl group is optionally substituted by a Ct-C4alkyl group, a halogen atom or a nitro group <Ct-Cs aíkcxíjkarbonilcsoport; -'Si<R3)s-os:o-port(ahol az Rscsoportok jelentése egymástői függetlenül CfCj eikíl- vagy fenlicsoporf; mono-vagy dl(Cs-C« aikoxl}(C5-C6aíkílj-csoport; tatrahidröfuranil-cs-oport vagy fetrahídropiranil-csoport-: - n is 0, 1, 2, 3 or 4, preferably 0 or 1; characterized in that a compound of the general formula (P) - in the formula A represents (C 5 -C 8 alkoxycarbonyl group, preferably methoxycarbonyl group, or (C 10 -C 12 alkoxyaminocarbonyl group and R represents as defined above - is reacted with a typease in vinyl acetate or acid anhydride base. and II) the resulting compound of general formula (2) or (2'j - in which Z is an alkyl group, such as a C1-C3 alkyl group, preferably a C1-C3 alkyl group - is converted into the corresponding compound of general formula (1). As shown in reaction scheme 1, the starting material for the preparation of ring A precursors is obtained by hydrogenation of methyl-3,5-dihydroxybenzoic acid or its ester derivative or its 4-alkyl-substituted homologue, which is carried out by a modified version of the procedure described by P. Wang and 4. Adams |4. Am, Chero. Sec., 116,, 3296-3305. (1994)], In step 1, the enzyme-catalyzed asymmetrization of 1-alkoxyl(or dialkylamino}carbonyl-3,5-dihydroxycyclohexane or its 4-alpha substituted homologue is carried out in a solvent such as a vinyl alkanoate, such as vinyl acetate, vinyl propionate or vinyl butyrate, or an acid anhydride, such as acetic anhydride, propionic anhydride or butyric anhydride, while a lipase, such as SAM It (ligand from Pseudomonas fluoresceins), CCt (from C. andlda Cylindracea), is present. PPL (lipase from porcine pancreas), PSL (lipase from Pseudomonas cepacia), GCL (lipase from Gotlchum candidum) are used at a temperature between 13 and 40 °C, preferably at 20 °C, for 72 hours, in which step we reach the corresponding alkyl-1-(or dialkyl)-(1S13S1SR}-3-3alkyl.'benzyloxy:-S-hydroxyl or .(1S,3S,4:R,SR)-4alkyl-3-alkylcarbonyloxy-5-hydroxyl-cyclohexane.carboxylate (or carboxamide) (see (2) -general formula], or the corresponding alkyl-(or dialkyl(1S,3S,5R)-5-alkylcarbamate-3-hydroxyl or (1S',3S,4R.,SR)-4a Ik Μ - δ - a Ik Ilka rb ο η 11 o xi~ 3 - h I dr χ ί- c ík I oh ex áa carb χ i Iá thóz (or carboxamide) (see 2' general formula]. The assymmetrization can be carried out by enanyl-selective enzyme-catalyzed hydrolysis of the esters of general formula (3) using a suitable enzyme, thus yielding the same family of compounds, Schemes 2 and 3 provide the general procedure for the synthesis of all diastereomers of general formula (I) in which R1 = H and R2 = 0P and which are prepared from the compounds of general formula (2) and (2') mentioned in Scheme 1. As can be seen from the reaction schemes, the conversion of compounds of general formula (2) or (2'') to compounds of general formula (1) can be carried out by one or more of the following steps, which can be used in part or in a completely different order, depending on the actual diastereomers: (1) protection of the hydroxy groups (e.g. TBPMS, TSOPS), (2) ester saponification, (3) inversion of the 3- or 5-hydroxyl group, (4) formation of a leaving group (e.g. OTos, OSros, Öble), (δ) ring closure with a base, leading to the desired biclkl.o-13. 1 ..öjhexane, (8) formation of the desired (A) substituent in place of the group (A) bearing a carboalkoxy or carbamoyl functional group. Steps (2) and (4) are conventional reactions well known to those skilled in the art. Step (1) can be carried out as described in J. Am. Chem. Soc. 94, 6198 (1972) or in Protective groups in Organic Synthesis, T. W. Greene, John Wiley Sons, New York. Cleavage (3) can be carried out as described in Synthesis, 1 (1881) or by a two-step procedure (elimination and hydrolysis). Step (5) can be carried out as described in Tetrahedron Letters, 3-5-(4-5), 82998302 (1895). Step (8) can be carried out as described in J. Gene, Chem. USSR 34, 1021 (1954). Scheme 2 shows the preparation of all diseastereomers with the a-3aS configuration (the cyclopropyl ring is oriented). Scheme 3 shows the preparation of all diastereomers with the 3aR configuration (H-or-lf of the cyclopropyl ring). As can be seen from reaction scheme 4, the phenylcyclohexane derivative ((1) substituted with hydroxyethyl at the 3a-position is generally Compounds of formula (Ia) where R ~ H and A«CH?:OK1 are also useful in the preparation of precursors of the A-rings of D-vitamin analogues modified at the €-1 position. This possibility is demonstrated by the starting preparation from compound of general formula (Ia) (R~H, P-TS-DPS, A=CH2O:H), which proceeds via the key intermediate (4.2). By Grignard reaction (for example Ry«Me or Et) we obtain diastereoselectively the tertiary alcohols of general formula (1.1), with simultaneous removal of the protection of the ester function. On the other hand, by methylation of compound of formula (4.2) we obtain compound of formula (4.3). The best result (88% yield) was obtained by the Lombardo method (Tetrahedron Lett., 23, 4283 (1882)1. Alternatively, by the Wittig or Tebbe reaction (J. Grg. Chem.,. 50, 1212 (TS85)j yields of 39% and 64%, respectively, were obtained. By dehydroxylation of the compound of formula (4.3), the desired compound of formula (Lm) is obtained as the main product along with the epitene (4.4) (ratio 85:15, not shown). On the other hand, the compound of formula (4.3) is 75-2: by hydrochlorination of 2.R- and 2S-hydroxymethyl compounds in a ratio of ke (73%). These e pl mer alcohols are separated to obtain the compounds of general formula (Lj and (í.k) after TBOPS etherification (81 %) and subsequent ether heterolysis (31 %). By addition of water to the compound of formula (4.3) with hydrochloric acid, we obtain the tertiary alcohols (I.II) and (hl) in a ratio of 75:26. The above procedure, by which 19-nor-A-ring precursors are prepared from 3,5-dihydroxybenzoic derivatives; is shorter than the previously described procedures. The practical importance of the above route lies primarily in the fact that most of the intermediates are crystalline and can be purified by crystallization, which is more convenient for large quantities than the usual chromatography on silica gel, and also ensures a high degree of enantiomerically pure SAG11. The compounds of general formula (i) are novel except for those compounds in which the configuration is 2S, 3aS, 4aS and A is a fornil, hydroxy, ethoxy or methoxycarbonyl group, R and R2 are hydrogen atoms and R1 is -6Si(R3)s. The following (!) compounds of general formula are preferred: - A represents -C'H2OH, -CWjOCOR', -COR' or an ethynyl group; - Rt represents the group C1-C3 or -(CH2)R-OP; - R' phenyl-swept; - R is a hydrogen atom; - P represents a hydrogen atom or a -S1(R3)3 group; - n is 0 or 1, The compounds of general formula (f) can be used in the synthesis of D-vitamin (IS-nor, 10,25(OH)2-Ds| for example according to the following reaction scheme 5, which is described in Tetrahedron Letters, 37 (42): 73377640 (1936). The invention also relates to intermediates for the preparation of compounds of general formula (I), compounds of general formula (2) and (3), wherein in the formula The meaning of (Ci~CsaikoxBksrbönH-esoport or di(C,-C3a l kil} amin ok arbön n ti - c ö po rt; - R represents a hydrogen atom or a C<-C<10>alkyl group; - 2 represents an alkyl group; and compounds of general formula (1) wherein A is as defined above and R is a C1-C4 alkyl group. In the present specification and claims, the terms "C1-C4 alkyl", "C1-C6 alkyl" or "C1-C6 alkyl" refer to straight or branched chain hydrocarbon groups containing 1-3 (or 1-4 or 1-8) carbon atoms, such as methyl, ethyl, propyl, isopropyl, butyl, isobutyl, tert-butyl, pentyl, isopentyl or hexyl. The term "C1-C6 alkoxy" or "C1-C6 alkyl" refers to OR or SR groups, in which R is the C1-C6 radical as defined above. The invention is further illustrated by the following examples. Preparation of intermediates of general formula (1) a) cis,.ois2.-3,5-Dihydroxy-1-(methoxycarbonyl}cyclohexane compound (1.A), where R ~ H, A « COGCH-q Methyl-5,5-dihydroxybenzoate was hydrogenated in MeOH according to the 3,5-dihydroxybenzoic acid hydrogenation procedure described by Peng Wang and Julian Adams [J. Am. Chem., Soc. 118, 3296-3305 (1994)]. MetÜ-S.ö-dihydroxyphenezenOate (57.8 g, 0.629 mol, 97%,). A solution of 5% Rh / Al2.Oa (5.76 g) in Me-OH (400 ml) containing 0.1% AcOH is added to a 1 liter autoclave. The autoclave is purged with hydrogen twice (the pressure is reduced from 130 atm to 40 atm). Subsequently, the hydrogen pressure is increased to 130 atm and the temperature to 30-85 °C. When the temperature increases during the process, the hydrogen pressure is reduced. When the pressure decreases to 50 atm, the hydrogen pressure is increased again to 130 atm. The hydrogenation is carried out for 12 hours at 60-85°C at a pressure of 130 atm, and then the temperature is increased. The temperature is raised to 150 “C, and the pressure rises to approx. 155 atm. The reaction is continued for a further 36 hours. The catalyst is filtered off. The filtrate is concentrated and the residue is crystallized from an ethyl acetal / isooctane mixture to give compound (1.A) (31.1 g. 50 % yield). Op.; 135.9*0: * UV (EtOH): 211.4 nm (ε = 90.9); IRISH (KBr): 3284. 1734, 1259, 1015 cm ''; 1H-NMR (DMSO): η 1.13 (3H, m); 2.0δ (3H, m): 2.30 (1H, m); 3.47 (2H, m>; 3.61 (3H, s); 4.70 <2H, ti) ppm. Proceeding similarly to the above, but replacing methyl-3,5-dihydroxymethyl benzoate with methyl-3,5-dihydroxy-4-methylbenzoate, we obtain the following corresponding compounds: a) methyl-{'everywhere cis-S^-dihydroxyl-e-methylcyclohexanecarboxylic' 1(1,8) compound <R=Me, A=COOCH3)j op : 123 °C: !Η-ΝΜΡ (600 MHz, CD-söD): δ 3.698 (2H, dt, 4«4,.0,12,δ. Hz); 3.666 (3H, s): 2.40 <2H, tt. 4=4.0,13.0 Hz); 2.23 (1H, m); (2H, dt, 4=4.0, 13.0 Hz); 1.54 (2H < q, 4 = 13.0 Hz); 0.88 <3H, d, 4=7.08 Hz) ppm; b) methyl-mindenhol cis-4-yl-3,5-Glyhydroxycyclohexanecarboxylate: [(1,C) compound <R. = Et, A=CGÖCHS)] op.: 94«96 ’C; \H-MMR (500 MHz, MeOD): δ 3.72 (2H, dt,. 4 = 10.9, 4.1 Hz), 3.66 (3H, s), 2.42 (ΊΉ, m), 1.86 (1H, fes), 1.78 (2Ή, dt, 12.4, Hz), 1.58 (2H, d, 4=9.0 Hz), 1.46 (2H, m), 1.02 :{3H. t, 4=7.5 Hz) ppm. f.exclude) Ll^J£i2keílA>m3i4H / s..észeie^^ I a) Me 111 - (1C'., 3 S, SR) - 3-ace t οχ I - 5 - h 1 dr o-xl -c Ik I oh ex á ncarb - oxl létet [{,2.A) vegulet (R=H, 2=Me, A»COOCH3)j Methyl-cis,cis-3,5-dihydroxy-cyclohexanecarboxylate [(1 A) compound (R=H, A=CÖOCH3)] (15.2 g, 87 parts) and porcine pancreas-derived Hpase (PPL, 16.8 units / mg, 9.12 g) were placed in an Ehrlenmeyer flask, and then 450 ml of vinly facet was added at room temperature. The flask was flushed with nitrogen gas. The suspension was stirred in the dark for 2 hours, then filtered through oeltra to remove the precipitate. The filtrate was concentrated by evaporation. The residue was separated by filtration through a silica pad (70-200 mesh, 45 g). Toluene (210 ml), then toluene / ethyl acetate 75 / 25 (v / v) (210 ml), then 50 / 50 (v / v) (210 ml), finally ethyl acetate (240 ml) are used to separate, and after radical opening, compound (2.A) (R=H, Z=Me, A=COOCH3) (22.3 g, quantitative yield) is obtained as a yellow oil. IR (film): 3447, 1734, 1243 cm'·; H-NMR (COCb): δ 1.4 (3H, m), 2.1 (3H, s), 2.3 (SH, m). 3.7 (3H, s), 3.75 (1H, m). 4.7(1 H, ra) ppm: |«b2S: +-22.4 (0=7.25, CHCi5}. lö) Methyl-(7 R,3-S,4S,5Rj-5-acetoxy-3-h-hydroxy-4methylcyclohexanecarboxylate (2.B) or (R~Me, Z=Me, A~CO:OCHal and (7 R,3S,4S<5R}-5-acetoxy-3-bidoxy-4-ethyl-cyclohexacarboxylate 12'.C) v-compound (R = Et, Z=Me, A=COOCH3j. Proceeding in a similar manner to step (La), but using SAM fi-i, P'S-Lt or CCt-f instead of PPL, and also as starting material a) mell i-( everywhere c;sz}-3,S-dihydroxy-4-methylcyclohexanecarb-Qxllatot' [(7.B} compound (R » Me, A«CGÖCH.3h b) methi I - <minde-n h o í-e í sz) ~dIh I ö rexi - 4-e t í í-3,5 - c 1 kioh exán karboxOá tot [{1.0} vegyüieí (R - Et, A=COOCH;5)} alkalmazva klindclési anyagként a ke vetkező -vegyületeket nyertük; a) meiíM1R,3S,4S,5R}-ü-aceiox-3-hydroxy-4--methyl·cyclohexanecarboxylate {(228}) (R-Me, Z-Me, A«CGO-CH3)1 IR (fOm): 3434, 1737, 1439, 7243, 7027 cm -1 ; ’iH-NMR (500 MHz, COCS3}; § 4.84 (7 H, dt,. 0-4,3, 4,-3 Hz); 3.82 (7 R, m); 3,89 <3H, s); 2,45 (1 H, m); 2,32 :{1H, d, >8,4 Hz); 2,OS (3H, s); 7,92 (2:H, öt, >4,0, 4,0 Hz); 7,77 (3Η, m); 0,98 (3H, d, J=7,0 Hz} ppm; MS(m / z): 237 <M+, 7};213; 799; 786; 170; 782; 727; 717; 83, 87; 87; 43 (alapcsúcs}; [ab2'5; -22,7 (¢=-0,3-8, CHC13); b} m e t 11 - (1R, 3 S, 4 S, S- R} - 5 - a ce t0 x i - 4 - e t -i I - 3- h 1 d r o x i ciklohexánkarboxiíát, ((270} vegyüieí (R=Et, Z=Me, A=COOCHs)j IR (film}; 3421, 2958, 2380, 7733, 1437, 7239, 7 027, 739 cm’’; ’H-NMR (500 MHz, COOia}: 8 4,98 (1B, t, 3=4,7 Hz}, 3,87 (1H, m), 3,69 (3H, s), 2,80 (1H, bs), 2,18 (2H, m), 2,02 (3H, s), 1,84 (2H, m}, 7,72 (7H, hs), 159 (2H, m), 7,47 {1H, m}-, 0,97 (3H, t, >7,5 Hz} ppm; MS (m / 2): 245 CM* +7), 233, 208, 784, 180, 141. 725, 77 1, 95, 37, 57, 43 (aiapcsö-cs); [ab25; -50,2 <c=108, GHCb}. »} M3.I..ghalános,,ké,pletű,,,(^zt^eL^n^alEMS..eLs4a.^nssüésa I la) M e 10 -{1S., 3 S, 5- R} - 3 - ace 10 xi - 5 - h I d re x 7 - c le J oh exá nka rhoxí! et [ {2, A} vegyoiet R = X, Ζ», A=CÖQCB3)7 To a solution of (3.A)- meso-dracetate (R=H, Z=Me, A=COOCH2) (92.1 mg, 0.36 mmol) in 3.0 mL of CH3CN was added 27.0 mL of pH = 7.0 buffer, followed by SA.M 11 (73.8 mg, 48.3 units / mg). The mixture was stirred at room temperature, and the pH was maintained at 7.0 by the gentle addition of 7.0 M NaOH. The reaction was monitored by TLC analysis. The reaction was quenched by addition of NaCl, saturating the reaction mixture. The reaction mixture was extracted with AcO-Et (3 x 50 ml). The combined organic extracts were washed with NaCl solution (3 x 10 ml), dried over MgSO, and concentrated. The residue was purified by HPLC using isooctane / ethyl acetate (6:4) as eluent to give the compound (2.Aj) (R=H, 2=Me, A-COÖCH3) (30.1 mg, 38.5%} as a colorless oil. IIb) Methyl-<1S,3R,4R,5.Sh3-butyloxy-S:-:hydroxy-4-methyl·cyclohexanecarboxylate, compound 1(2. B) (R«^fe, Z=n-C3H7. A=COOCH3)] The compound (1.8·) <R«Me„ A-«COOC:B3) (0,2. g, 1,10 mmol) 2 mi CHjCts-ben készült oldatához vajsavanhldridet (538 μΙ, 3,29 romol) adagolunk szobahőmérsékleten, majd TMSoTf (triraetilszilif-trsflaf) oldatot adagolunk (25 μ), TM). A keveréket szobahőmérsékleten 30 percen át keverjük, majd 2,5 ml MeOB-f adagolunk, és a keveréket további 2 órán át keverjük, majd 5 %-os N:aHCO3oldattal lefojtjuk a reakciót A reakció ©legyet. NaCi-oWattai mossuk <3x20 ml), fágSO*-gyei szárítjuk, majd föményítjűk, A kapott maradékot s-zil'lkagéíen kromatográfiásan tisztítjuk •feluenskénf izoefctán / AcOEt-t 8:1 arányü elegyét alkalmazva. Így kapjuk. (3.B) dlbofiráí vegyületet (R=Me, 2~n-C3H7> A~CÖÖCK3) (3.9 g, 38.8 %.) as a colorless oil. To a solution of this meso-diester (110 mg, Ö.34 mmol) in 2.0 ml CH3CN was added 22 ml buffer (pH » 7.0), followed by SAW 11 (<37 mg, 46.8 units / mg). The resulting mixture was .The reaction mixture was stirred at room temperature and the pH was maintained at 7.0 with a measured amount of 1.0 M NaOH solution. The reaction was followed by TLC analysis. The reaction was stopped by the addition of NaOH. The reaction mixture was extracted with ethyl acetate (3x50 ml), dried with MgSO4 and concentrated. The residue was purified by HPLC using isooctane / ethyl acetate 7:3 as eluent. Thus, the moncbufirate (2,B) was obtained. <R«Me, 2«n~C3H7, A»CÖOCHS) (78 mg, 30 %) színtelen olaj formájában. IR (film): 3495, '2964, 2378, 1731, 1433, 1281, 1183, 99G cm-1. ``Ή-NMR (C'DCis); 4.83 (1B, dt), 3.83 (1H, m), 3.68 (3H, s), 2.46 (1H, m), 2.32 (ÍR, m)„ 2.28 (2H, t, J=?,'9 Hz), 1.-91 (2H, m), 1.82-1.62 (5H, m), 0.85 (OH, m) (ajD2Sl +18,,2 <c«2,0-9, CHCI3) MS: 259(IVT+1), 227, 214, 187, 170, 152, 127, 111, 93, 71, 43. I le) Methyl-(1§,3R'.,4.R,.SS}-3-acetoxy-5-dihydroxy-4-methylcyclohexanecarboxylate [(2.C) compound (R~Me, 2»Me, A~CÖÖCH3)j From (3.C) mesodiacetate (R~Me, Z*M:e, A-GOOCHs) is prepared according to (11.a), [ob2S: +20 (0=2.9, CHCl3). II d) Ml eti I - (1R, 3 S, 4 S, 5 R > 5 - acet ο x I - 3 - h I dr ox .s - 4 - met 11 cyclohexanecarboxylate, (<2!.S) compound <R«Me, Z-Me. A^COOCKs)) The diacetate (3.0) (R=Me. Z~Me, A=OOOOH3) is prepared as in (IIa), but using PPL as lipase. [p.)oss: -13.5 <0=2.88, CHCh). Example 1 (2-S ..3-aS',4aS}-2-tefc-B:utild.imetiisHi:oxy-'3a-carbome'ethoxy~bicyclo[3.1.Ohexane «ibl> chemical (A=COOCH3, R=H, P=T-8DMS)j a) Methyl-(1R>3S,5R>-3-acetoxy-5-tosyloxy-cyclohexanecarboxylate, t(2.4.a) desired (R = H, L-OTos, A=COOCKs)j p-Toju-olsulfonyl-clondol (13.3. g, 70 mmol) is added to a solution of methyl(1S,3S,5R}-3-acetoxy-5-hydroxy-cyclohexanecarboxylate ((2.A) compound (RH, Z=Me, A»COOCH.S)| (10.1 g, 43.7 mmol) and dimethylaminosopridine (6.1g) in a mixture of triethylamine (56 ml) and m-ethylene chloride (10 ml) at 0 'C. The mixture is stirred for 1 hour. 'C, then stirred at room temperature for 22 hours. The reaction was quenched with water (300 ml), then the mixture was extracted with methylene chloride. The organic layer was washed with water, dried over MgSO-«, filtered and concentrated. The crude product was crystallized from EtOH to give (2.4.:a) (R=H, L^OTos. A=COOCHS) (13.2 g. 81.6%}. Op.: -83,-PEN.; IRE (KSr): 1734, 1 17S cm7; 'H-HMR (CDCU): § 1.5 (3Η, m), 2.0 (3H, s), 2.2.8 (4H, m), 2.47 (3K. s), 3.68 (3H, s), 4.4 (1H, m), 4.68 (1H, m), 7.35 (UH, d, 3=8,SHz), 7.8 (2Ή, d. 3=6.5 Hz) ppm, b) Methyl~( 1R,3.S,5R}-3-hydroxy-5-tosyl0Xf-clklO:benzenecarboxylate, ((.2,.5.3-) compound (R»H, L=OTos, A~COOCHa)j (2.4.a) desired compound (RH, L=OTos., A=COOCH3} (23.38 g, 63 mol) in MeOH was added potassium carbonate (4.36 g, 31 mmol). The suspension was stirred for 30 min, then poured into water (1.5 liters). The precipitate was filtered and dried. Thus, we obtained the compound (2..-5.3} (RH, L=OTos, A=CO-OCH3) (16.5 g, 89 %}. M.p.: 98.4 °C; UV (EtOH)·: 225-nm (s = 11S35); IRISH (KSr): 3447, 171 8, 1176 cm*1; 'N-NOTHING. (CDCb).: δ 1.52 (4H, m), 2.25 (4H, m), 2.45 (3H, s), 3.5 (ÍR, m), 3.68 (3H, s), 4.42 (1H, m), 7.35 (2H, d, 3-8.5Hz), 7.8 <2H, d, 4=8.5Hz} ppm; [aj / s: -IS (¢=1.08, EtöH). •c> Methyl (1R,3R,5R)-3-Penzoyloxy-5-tosyloxy-cyclohexylcarboxylate, ((2.®.a) phenylacetate (R=H, L=ÖTos, A=COOCH3)j To a solution of (2.5.a) compound (R=H, L=ÖTos, A=COOCH.S) (18.35 g, 56 mmol), triphenylphosphine (18.4 g, 70 mmol) and benzoic acid (3.53 g, 70 mmol) in toluene (180 ml) and tetrahydrofuran (70 ml) was added diethyl azodicarbonate (1 ml, 70 ml). The mixture was stirred at room temperature for 30 minutes, then captan (73.5 ml) was added, the mixture was filtered and the residue was concentrated. Toluene was added to the crude product, and the solution was filtered through a silica pad (30-70 mesh). Toluene was added to the crude product, and the solution was filtered through a silica pad (30-70 mesh). Toluene was added to the crude product, and the solution was filtered through a silica pad (30-70 mesh). The residue obtained by elution with a toluene / methylene chloride mixture and subsequent concentration is crystallized from EtOH, and thus the compound (2.5.a.) (R=H, L~OTos, A-CÖQCH-,) <19.7? g, 82 %). Op.: 76.2 <C: UV (EtOHj: 227 nm ·{«. = 20840); IR (KBr) 1708, 1177cm': 'H-MWR (CDCIj): δ 1.7 (3H, ml 2.14 (2H, m), 2.35 (3B, s), 2.48 <1H, m), 2.83 <1H, m), 3.18 (3H, s), 4.75 (1Η, m), 5.43 (1H, m:}. 7.2 (2H, d, J-11.4Hz), 7.5 <2R, d, J=8.5Hz), 7.8 (1H, m), 7.75 <2H, d. 3==11.4Hz), 7.94 <2H, d, 5~8.5Hz) p:pm: -85.8 <o»ö,98, EtOH). d) Melyl-(1R,3R,5R)-3-hydroxyl~5-azilioxl-cyclohexanecarboxylate: {<2.7.a) chemical (:R~H. L=Olos, A~COOCH3], To a suspension of compound (2.5.3) (R=H, L=OTes, A-CO0CHa> (19.77 g. 48 rumot) in MeöH (<260 ml) was added potassium carbonate (3.18 g, 22.9 mmol). The mixture was stirred at room temperature for 6 hours and then poured into water (<1 liter). The aqueous layer was extracted with isopropyl oxide and then dried over KgSO^, filtered and concentrated. Thus, compound (2.7.a) (RH, t»OT'os, A=ΟΟΟΟΟΗδ) was obtained as an oil (<17.45 g, quantitative). UV (E1OH). 224 nm 12262): IRISH <kbr>;3525, 1731, 1174 cm-1; (CDCU): 3 1.67 (3H, m), 2.1 <3H, m), 2.45 (3H, s), 2.85 (1H, mj.. 3.7 (3H, s), 4.3 (1H, s), 4.82 (1H, m), 7.35 <2 H, d, J = 8.5Hz), 7.8 (2H, d, J-8.5Hz) p.c.m.; C 10 25 : 36.7 (e~1.08, CHCl 2 ). ej Mell|-(1R,:3R,5R)-3-tert-butyldimethylsilyloxyloxa-5-tostrioxycyclohexanecarboxylate «2,8.a) chemicals (R~H, L-GTos, P-TBDMS, A~COOCH3)j To a solution of compound (2.7.a) (R~H, L~OTos, a=COOCH5) (17.45 g, 46 mmol) and imidazole (3.9 g, 57 mmol) in dry dimethylformamide (80 ml) was added t-butyldimethylsilyl chloride (8.8 g, 57 mmol). The mixture was stirred at room temperature for 1.5 hours, poured into water and extracted with toluene. The organic layer was washed with water and then concentrated. The crude The product Λ is crystallized from heptane to give the compound (2.8.a) (R~H, L-OTos, P-TBDIViS, A«CÖ-ÖCH3) (13.34 g, 68 %}. Op.: 86.2 C: ÜV (EtOR): 225 nra (s = 12390); ÍR <:KBr): 2853, 1726, 1436, 1359, 1173, 831 cm'5; 'H-H'MR (COCi3).; δ 0,02 (3H, s). 0.05 (3H.s), 0.82. (9H, sí, 1 (4H, m), 1.85 (2H, m), 2.45 (3H, s), 2.8 <1H, m), 3.67 (3H, s>, 4.2 bs), 4.7 (1H, re), 7.33 (2H.5, JS.5Hz), 7.8 (2H, d, J=8-,SHz) ppm V«b2S: -41,,6- (e~-1,ÖG, EtOH). f) (2S,33S,4aS)~2~tsrc-8ytHdímetíisziíiloxi-3a-karbométoxl- blelklc[3.l .QJhexán, ({lb 1) vegyülat {R=R, P=T8DMS, .A=COOCH3)j {2.8.a) vegyütet {R=H, t=OTos, P=TBDfdS, A=COOCHa) (378,5 g, To a solution of 868 mmol of t-butane at 84°C, a 1 M solution of potassium tert-butylate in t-butane (1.02 liters) was carefully added dropwise over 1 hour. After 5 minutes of addition, the suspension was cooled to 30°C and saturated ammonium chloride solution (3 l) was added. After 10 minutes, the aqueous phase was extracted with isopropyl alcohol. The organic layer was washed with water, dried over MgSO4, filtered and concentrated. The residue was flash chromatographed on silica gel using baptan / ethylacetal as eluent to give compound (b.1) (R"H, P=T80MS, A-COOCH-s) as a yellow oil (211.3 g, 91.3%). 5b?e;-. 135 'C; UV (EföH): 201 nm (s - 742); IR (film) 172.8 ere', 1458 cm'5, 1437 cw', 1254 cm'5. 837 cm'1; 1:H-NMR (CDCl 3}: δ 0.01 (6H, s), 0.83 (SH, s). 1.28 (2H, m), 1.8 (2H, m), 2.11 (3H, m), 3.65 <3H, s), 3.9 (1H, m) ppm; (p.]s25: -43 {¢=1.04, EtOH). Example 2 (2S,3aS,4aS)-2-tert-butyldimethylsilyloxy-3a-(hydroxymethyl)·· bicyclo[3.1. To a solution of (ca. 2) compound (RH, P-TBDMS, A=CH2OH) {2S,3aS,4aS}2-tert-butyl-3-carbonitrile (3.1.0)hexa ((1.b.1) or (R~H, P=TBDMS, A=COOCH3) (207.5 g, 768 mmcf) in a flask (2.1 liter) at -70 °C was added a 1.5 M solution of dihydrobenzyl aluminum hydride in toluene (1.25 liter) at 1.6 °C. After addition, saturated potassium hydroxide solution was added slowly and the temperature was raised to 5 °C. The reaction mixture was stirred for 2 hours, then cooled to 10 °C. extracted, then the organic layer is dried over MgSO'4 and concentrated. Thus, 142.8 g (88 %) of the compound (tb2) according to dm is obtained in the form of a yellow oil, IR (KBr) 3355. 141 1255, 835, 774 cm' (C'DCU): δ Q (SH, s), 0.32 (1H, m), 0.5 (1H, m), 0.83 (SH, s), t.16 (1'H, m), 1.87 (SH, m>, 3.64 (2H, m), 4.0 (ÍH, m) ppm. (2S,3S,4aSi-2-tert-butyldimethylsilyloxy-3aformylcyclo(3.1.Gjhexene [Ab.3]) compound (R»-H, P-TBDhfS, A«CKO)| To a solution of compound (1.b.2) (RH. R«T8DM'S-, A=CH2OH) (68.6 g, 287 mmol!) in mehlenium chloride (700 ml) at room temperature was added pyridinium chloride (68 g, 31-5 mmol). The mixture was stirred vigorously for 1 hour. The temperature rose to 35 °C; then dropped to 25 °C. The suspension was filtered through a pad of celite and washed with methyl ether and isopropyl ether. The organic layer was washed successively with water, saturated aqueous sodium bicarbonate and water until the pH was 6-7. The combined organic layers were dried over MgSO4, filtered and concentrated. The residue (68.8 g) was purified by flash chromatography using heptane / ethyl acetate 95:5 as eluent to give (kis.3) as a yellow oil (50.33 g, 73%). (RH. P-TBDMS, A~CHÖ) W (EtOH)·; 204 sqm (s « 5282): Iceland (KBr). 1728, 1253, 1119, 838 cm'': 'H-NMR (CDCI3): ö G (8H, s), 0.87 (SH, s), 1.3 (2H, m), 1.85 (2B, m), 2.1 (3H, m){. 4 (1H, m), 8.9 (1H, s) ppm; (α]οϊ5: -49.4 (e~1.06, EtOH). A géjda (2R,3aR,4aR)2~farc-B!JtíídimetrlszylUoxi-3a-carbomethoxymc1clo(3.l:.Gjhexán- [Ah. 1) vegulet (RB, A=COOCHS, P« TBDMS)) a) MeíH-ílR,3S,5S)~3-aceioxi-5~beR2Oi:oxy-cyclohexanecarboxHaf 1(3.9.8) vegulet (R~H, A=COOC-Ha.)j A (2.8.a) ve-guletnél (R~H, L^ÖTos. A~COOCHS)- leírtak szerint, convertáljuk am«tíí<1S,3.S,5R)«3-acetoxj-ő-h}droxÍciclohexánkerboxliáteí ((2.8.a) ve-guletnél (R~H, L^ÖTos. A~COOCHS)- leírtak szerint, convertáljuq am«tíí<1S,3.S,5R)«3-acetoxj-ő-h}droxÍciclohexánkerboxliáteí ((2.8.a) ve-guletnél (R~H, L^ÖTos. A~COOCHS)- leírtak szerint, convertáljuk am«tíí<1S,3.S,5R)«3-acetöxj-ő-h}droxÍciclohexánkerboxliáteí ((2.8.a) ve-guletnél (R~H, L^ÖTos. A~COOCHS). Z=Me.;A=COÖ'CH3jj (25 g 111.3 mmol) mephi!~(1 R,3S,5S) S-acefoxBS-benzoiioxsclklohexanecarboxllate in(3.9.a) vegulet (RH, A-COGK3)] (32.4 g, 91 g: CO 1.88 <3H, m), 2.05 (3H. s), 2.34 (3H, m), 2.92 (1H, mj, 3.70 (3H, s), S.,1-8 (1H, m>, 5.55 (1H, m), 7.50 (3B, m), 8.05 (pm, 2) pH; Ajo2S: +42,-3 (c*0,.3.2,. CHCf3). b) M e 111 - (1R, 3 S. 5 S) - 5 - ö e η z ο i I οχ i - 3 - hidr ο x I ciklobexársksrboxliát.i(3.10.s) vegyület (RH, A=C0Ö'CH.3)j. A meti I - (1R3 S, 5 S) ~ 3 - acetoxi - 5 - be η z ο lí ox i - c-í k ío hexahkarb ο xi I á to í ((3-.0.a) vegyület (RH, A~COOCH3}j (32.4 g, 151.9 mmoi) a (2.5.a) ve13 gybíetaéí <R=H, L~OTos, A-COOCHs) leírtak szerint szappanesítjuk el A nyers terméket ssíitkagéíen filash kromatografáljuk -{eiuens: heptán / etii-acetát ~ 5:5), és így kapjuk a [{3.10.aj vegyületeí (R = H. A ~ CÖOCBa}) (22,38 g, 79,5%).. 'H-'NMR (CDCU); δ 1.53 (4H, m), 1.92 (1Ή, S), 2.3 <2H.. m), 2.36 (1H, m), 3.7 (3H, s), 4.1 (1H, m), 5.53 (1H, m), 7.5 (3H, m), 8.0 (2Ή, m) ρ ρ m; l«lo2S·; -13.5 (c=1.43, CHCR). c) Metíi-(1 S,3S,5S)- S-benzoiioxi-S-tozlloxi-eiklohexénkarboxiíáf: ({'3.11,a) vegyület (R = H, L=GTos. A-COQCRsj) The alcohol (3.10.aj) (R~R, A-CGOCH3): (25.2 g, 80.88 mmol) was tosylated as described in (2.4.a) with the compound (R~H. L=OT'os, A-COOCH?,}. After flash chromatography purification {eluent: heptane / ethyl acetate - 7;3) and crystallization from heptane / EtGH mixture, the compound (3.11.a) (R«H, L«OTos, A~CöÖCH;i) (39.75 g) was obtained in quantitative yield. M.p.: 128.4 °C; IR (Circ): 2950, ​​1715, 1175, 939 cm'1; 'M-NMR (CDCl3): δ 1.7 (3H, m), 2.18 <2R, m), 2.33 (3H.s), 2.5 pH, m), 2.85 (1H, m), 3.68 (3H. s), 4.76 (1H, m), 5.43 (1Ή. m), 7.19 (2H. ti), 7.5 (2H. d), 7.58 (1H, m), 7.77 (2H, d), 7.98 <2H, d) ppro;. (ajc*8: +69 (he =1.014, CHCR), d} M e ti í - (IS, 3 S, 5 S) - 5 - hydr ro xh 3 - to zilo xy -ci k I ο hex á n kar tok ii á á t [compound (3.12.a) (RH, L=OTos, A-CÖGCH3)] From the compound (3.11.a) (RH. t«OTos, A = COOCH3) (35.25 g, 83.4 mmol) in the compound (2.7.a) (R«R, L«OTos, A-CGOCH3) te Utak obtain ukame 111~(1S, 3 S, 5 S) - 5 - 51 dr ο x I - 3 - te zi I oxi - ci ki eh hex á n carbox) vidotet {{3.12.3) compound (R.«H, L~OTos, A=COOCH5)) (23.25 g) in quantitative yield as a yellow oil. H-NMR (OOCl 3 ): δ 1.6 (4H, re), 2.08 (3H, m), 2.47 (3H, s), 2.33 (1H, m), 3.68 (3H, s). 4.3 (1H, m), 4.82 (1H, m), 7.35 (2Ή, d), 7.8 (2Ή, d) ppm. e) M éti I - (1S, 3 S, 5 S) ~ 5 - tere - bis ti id im et iisziiit ο x i- 3 - toz 11ох i cyclohexanecarboxylate [(3.13,a) compound (RH, L«OTos, P-7BDMS, A=COOCH3)j From the compound (3.12.a) (R=H, L-GTO-s, A~COOGH3> (29.2 g, 89.07 mmol) we proceed as described for the compound (2.8.a) (RH, L-GTO-s, P-TBDMS, A=COGCH3). By flash chromatography purification on silica gel (eluent: heptane / ethyl acetate = 8:2) we obtain the compound (3.13.aj) (RH, L-GTO-s, P-TBDMS, A=COOCH3> as a yellow oil (34.8 g, 88 %}. IR (film): 2953, 2855, 172S, 1273, 1177, 849 cm''; (COCh): δ Ο <·6Η. d}, 0.83 (SH, s), 1.55 <3Η, m), 1.88 (2Η, m), 2.38 (1Η, s), 2.48 (3Η, s), 2.82 (1H, m), 3.7 (3H, s), 4.2 (1H, m), 4.7 (ÍR, m), 7.8 (2B, d) < 8.09 (2R, 0) ppm; +29.5 (0=1.8-8, EtöH). í) (2R,3αR,48R)-2-tereo-ButyldimethylS2ylyloxy'-3α-carbomethoxy'· bierk;e[3.1.0]nexáe, í(Lh.U) or its (R~H, P=TBDMS, A=COOCH3)j Compound (3.13,a) (R=H, L=OTös, P-T8DMS, A=CG0CH3) (33.í g, 75 mmol) was treated as described for compound (1,b. 1) (prepared as (2.8.1)). Flash chromatography on silica gel (eluent: heptane / ethyl acetate = 85:5) gave the compound {2R«3aR,4aR}-2-tert~ tfUtildlfnetHszflHoxs-3a-k.arboífn:ethoxy!'-bicyclo(3.1..Öjhexáfft |{lh,1)}, (R=H, P-TBDIUS, A=CQGCM3)í as a yellow oil (15.5 g, 78 %). IR (film): 2882, 2856, 1724, 1113, 837 cm'1; 1 H-NMR (CO.Cl 3 ): 0 0 (8H, s), 0.85 (911. s), 1.11 (1H, d), 1.27 (2H, m). 1.5 <3R, s)„ 1.8 (1.H, m), 2.11 <3H, m), 3.85 (3R, s), 3.9 (1H, m) Ppm jö]D25: +38.3 (0=1.122, EtOHj. Example 5 (2R,3aR,4aR)-2-tert-butyldimethylsilylblock i-3a-(hydroxylmethyl).bicyclo[3,1.0]hexane [(1.1x2) compound (R=H, F-TBDMS, A=CW2ÖH] The (2Rx3a'R..,4aR)-2-tert-butylmethylsilyl-3a-carbomethoxy·bicyclo[3,1.G]hexene [(lb 1) compound (R=H, P-TRDMS, A=COOCHS] (15.15 g, 58 mmol) was converted into the compound (lb2) (R=R, P=TBDMS, A=GHaOH) form as described for compound (lb2) (R=H, F=T8ÖMS; A~CHSOH) (11.85 g, 87%). IR (film): 3354, 2828, 2856, 1255, 835 cm1; 1H-NMR (CDCl5): S 0.1 <6H, s), 0.35 (1H, t), 0.5 (IR, t), 0.38 (SH. $), 1.17 (IR, s), 1.85 <5H, m), 3.52 (2H, ra), 4.0 (IR, m) ppm; [α 2 *· + 17.4 (c=1, 15, EtOR). Example 6 (2R,3aR,4aR)-2-tereobutyrate Imef II s tyloxy-S-formyl Ibidk[3.1.1-hexane [(1h,3) compound (R = H, P<TSDMS, A=CWO)j Compound (lh2) (R=H, P=TBGMS, A=CH2:OH) (11.3' g, 45.5 mmol) was obtained by proceeding as described for compound (Lb.3) (R=H« P-T8DMS, A=CHO), compound (l.h.3) (R«H:P=TBDMS. A«CHO) as a yellow oil (6.2 g, 55%). UV <etoh>: 204.5 mm (ε =· 5600); IR (film): 2930. 2880, 2358, 1705, 1119, 10S7, 838 cm'1; 'H-NMR (GDCÍs): & 0 (8H, s), 0.83 (8H, s), 0.85 (1H, t), 1.22 (2R, m), 1.85 (2H, m), 2.1 (3R, m), 4.0 (ÍR, qomíopSet), 8.87 (1H, s) (John: 52 + S). (0=1.003,. EfOH).. (2R, 3cS,4aS)'2«crc»butHdimstHszylHoxü3s-xrbomeí:oxybicicfo<3,1.0')b-exene [(1,3.1} vegulet.{RH, P=T8DMS, A«C-GOCHc)j whose). Metu-(1 R..3S!5R}-3-terc-buthd'methylszfliiox'i-5-tozflPxicicloh-exáncarboxyphate [(2.3.3} vegulet (R-Ή, L-OTos, P-TBGMS, A^CGOCHA; A m et H - {1R, 3 S, 5 R) - 3 -- h í droxi - 5-1 o 2i i ox i - c ik le b ex á nka rbo xÜ át (-{2.5. a} vegyulet (R=H, l=OTos, A~CQQCH3)j (29.3 g, 89.2 mm} (2.8.a} vegüietnéí (R~H, L-OTos,. P~7BDMS, A-COÖCHs) leírtak szerint védve kapjuk a (2,3.a} veguuletate (R®H, t-OTos. P=TBÖ»S, A-COÖCHs} (36.75 g, C3%). At,: 70.3 'C; IR (K'Br): 2957, 2855. 1734, 1174, 923 cm''; 'H-HMR (CDCk): δ 3 (6H, s), 0.82 (9H, s), 1.41 {3H„ m). 2.16 (4H, m), 2.48 (3H, s>, 3.54 (1H, m}, 3.63 (3Ή, s), 4.41 {1H, m}„ 3.89 (3H, s), 4.41 (1H, m), 7.34 (2H, d), 7.3 (2H, d) ppm; (ab25? -8.2 (c = 1.2, EtOH). b} (2 R, 3 a 8, 4 a S}- 2 -1e rc- bu ti ld I me ti I s zHí io xi- 3 a - ka rbome to.x'ibrclklo[3.1 .Ojhexane [pa1} compound (R~H, P-TBGMS, A=CG0CB3)1 Starting from the compound (2.3.3) (R=H, 1-OTos, P-TBDMS, A-CGÖCB3) (34.81 g, 78-,:6 mmol) we obtain the compound (1bí) (RH, P=T8OMS-, A~COOCB3) as described. By flash chromatography on silica gel (eluent: heptane / ethyl acetate ~ 5:5) we obtain the compound (Iaí} <R = H, P«T8OMS, A=COOCH®} sárga olaj formájában (16,6 g, 78 %}. IR- (film): 2953, 2855, 1726, 1148, 836 cm -1 ; 'HN-MR (CDCia): δ 0 (6H, s), 0.86 (9H, s), 1.5 (5H, m), 2.1 (1R, m), 2.48 (TH, m), 3.68 (3H, s}, 4.33 (1 H, t) ppm; [ajoíö: -80,1 (c«0;9S8, EtOH). Ι,-ΜΙΜ (2R!3aSv4aS}-2-ter.c-bu'tiídimeti'is2ll1lox.i-3a-{bí.droximetii}•fc-ictki-o[3.-1.Ö]feexén.: [{1.3.2) vegyidet (RH, P-TBOMS, A-~CRzOH:}j Az (La. 1) vegetable oil (R«R, P-TBDMS, A~GHZGH) (15.6 g, 57.7 pounds) water, az (í.b.2) vegetable oil (R~H, P-TBDk? 2} Vagy ül etet (RH, P-TBÖMS, A-CHyQK) share the formula (11.7 g, 63.7 %}-. IR (film): 3331, 2927, 2855, 125-4. 1094, 1006, 835 cnT'; 1H-MMR (CDCIs): δ 0 (6B, s), 0.5 (1H, m), 0.88 (9H, a), 1.19 (3H, m), 1.72 (2H, m), 2.1 (2H, m), 3.6 (2H, s), 4.34 (1H, t) ppm; [odö£S: "23.5 (c~ 1,062, EtOH). 9. (R=H.P-TBD^S, CHOB Starting from the compound (ie2) (R»H, P«TBDMS, A-€H2OH) (11.1 g, 46.5 mmol), proceeding as described for the compounds (lb3} (RH, P=TBD&1S, A=CHO) gave the compound (La. 3). (R = R, P=T8-DMS, A~CHO) as a yellow oil (8.8 g, 3014). UV (EtOH): 204.7 nm (s - 6981};· i?R (film}; 2828, 2855, 1702, 1255, 1072, 8:37 .cm''; 1H NMR (CDCl 2 ): δ 0 (6H, s), 0.85 (SH, s). 1.45 <1H, we, 1.78 <3H, m), 2.02 (2H, m), 2.5 (1H, m}, 4.35 (IR, m), 8.81 (1R, s) ppm; Ms25: -71.8 (0=1.406, EtOH}. 1E-hekia (2S,3aR,4sR}-2-tert-butylmethylmethodszPxl~3a-carbomethoxy" bi,cyclo[3,1.0>hexane [(I.?. 1) chem. <R«H, P=TBDMS, A=GOOCR3)j a) Methyl-(1 R,33,5R)-3-acetoxy-5-tert-butyldimethyldioxycyclohexanecarboxylate ((3.7,3} compound (R = H, P~TBDMS, A=COOCH3) The hydroxyl group of the desired compound (R = R, Á~COOCH3) of MefH-C 1S,3S,5R.}-3-acetoxyl-5-h{drQxycyclo-benzenecarboxylate (2.A) (45.5 g, 0.210 mmol) was synthesized as described for the compound (2.8.a) (R=H, LOTas, P=TBDMS, A=COOCH.3>). Purification was carried out by flash chromatography on silica gel using a 9:1 mixture of heptane / ethyl acetate as the solvent, and thus the compound (3.7.a) (R~H, P-TBDMS, A=COOCH3) was obtained as a yellow oil (69.9? g, 02%}. IR (film): 2953, 2856, 1738, 1240 cm''; • H-NMR (CDCIj): δ 0 (6H, s), 0.8 (9H, s), 1.33 (4R, m), 2 (3H, s}„ 2.1 (2H, m), 2.32 (1 R, m), 3.55 (ÍR, m), 3.52 (3H, s), 4.56 (1H, m) ppm, b) Methyl-(1 R,3S,§Rj-S-tert-butyldimethylsilyloxy-3-hydroxycyclohexanecarboxate ((3.3.a) chemical (R=H, P~TBDMS, A=COOCH3)j Starting from the compound (3.7.a) (R=H, P=TBDMS. A=COOCHS} (63.67 g, 0.1926 mmol) we proceed as described for the compound (2..§..&} (R=H, L-07os, A-CÖÖCHj.) ed. The purification is carried out by flash chromatography on silica gel using a 7:3 mixture of heptamethyl acetate as eluent., and thus we obtain the compound (3.8.a) (R=H, P-TBDMS, A=COOCR3) in the form of a yellow oil (46.24 g, 83 %}.. IR (film): 3404, 2952, 2858, 1738. 837 cm'; (CQCis): δ 0 (6K, s), 0.81 (9H, .$}, 1.3 (3H, m), 1.67 Í1H, m), 2.13 (4R, m), 3.58 (2'H, m), 3.63 (3H, ss ppm; η / E + 6.8 (c=1.038, CHCIS). c} Me ti I - (1S, 3 S,.5 R} - 5 -1 erc - bu 1.11 dimethyl 1 sí H1 oxy - 3 - to zi 1 o xi clklohexanecarboxylate ((3.8.3} chemical (R=H. i~OTos, F=T8DMS, A=COOCH3}] Starting from compound (3.8.aj (R~H, P=T8DMS, A«COOCHS> <4 5.SS g, 0.159 mmol) we proceed as described for (2.4.a) l.~OTos. a-CQOCH3) eb The purification is carried out by flash chromatography using a 3:2 heptane / 'ethyl acetate mixture as eluent, followed by crystallization from EtOH· to give compound (3.6.aj (R~H, L-ÖTos, P^TBDMS, A”COOCH3) (§3.7 g, 76%), Op.: 71;C: IRELAND (Circle): 2957, 2855, 1734, 1174, 923 00%': H-NMR (CDCl 1s ): δ G (6H, s), 0.82. (9R, s), 1.41 (3H, mj, 2.18 (4H, m), 2.46 (3H, s), 3.54 (Ι·Η, m), 3.89 (3H, s), 4.41 (ÍR, m), 7.34 (2Ή, di, 7.8 (2H, d) ppm; 102:S: +6.8 (c~1.032, EtOH). d) (2S. 3 a R,4aR}~2~tert~bet Ildimethylsilyloxy-3a-carbometoxybiocyclos.I.Ohexane; [(1,1.1} compound (R~R, P-TBDMS, A-CGOCR3)j Starting from compound (3.8.a) (R=R, L~OTos, P-TBDMS, A=COOCK3) (53.7 g, 8.121 mmol), the procedure described for compound (lb 1) (R~H, P-7SDMS, A=OOOCH3) was followed. Thus, compound (lf 1) (R~H, P^TBDMS, A-CQöCRj} was obtained as a pale yellow oil (24.48 g, 74.6%). IR (film): 2953, 2566, 1726, 1148, 838 cm';; (CÓCis): § 9 (8R, s), 0.86 (9H, s), 1.5 (5H, raj,. 2.1 (1H, mj, 2.48 <1H. mj, 3.68 (3H, s>, 4.33 (1R, t) ppm; [ab25'.: +62.9 (c < 1.085, EtOH). (2S«3aRt4aR}-2-te:rc-phenylmethylsth:liÍ0xi-3a-hydroxymet!bbiolikiojS, 1.Qjhexam [{lf2} compound (R~H, R-TBOMS, A~CR2OH}j Starting from compound (1.f.1) (R~H, P-TÖDMS, A«COOGHa> (10 g, 0.G37 mmol) we proceed as described for compound (1b2) (R=H, P-T8DMS, A«CH$OH). Thus we obtain compound (1f2} (R~R, P«T8DMS, A=CB2O:H) in the form of an oil in quantitative yield (10 g). iR(film): 3331, 292:7, 2858, 1264, 1094. 1008, 838 cm'; 1 H-NMR (GDC1g); S 0 (SH, s), 0.5 {WRIT. m). 0.88 (SH, s), 1.18 (3K, m>, 1.72 (2R, m>, 2.1 <2H, m), 3.6 (2R, sj, 4.34 (ÍR, t) ppm; painful25: +23.2 (0-0.39, EíOH) IZUíéloa (2S,3aR,4aR)-2tert-8utildtmeíílsztllioxf-3a-formyl» b:csklo[3,1 .Olbexén [{if3} vegy selelet (R~H, P=T80MS, A»CHO)j Proceeding as described for compound (Lb.3) (R~H, P-TBDMS, A-CHO), compound (l.f.2) (R=H, P=TBDMS, A-CH2OH) (10 g, 0.037 mmol) was transformed into compound (lf3) (R~H. P«T8GMS·, A=CHO), which was obtained as a pale yellow oil (5.3g, 59.7%). ro), IS IR(ftlm): 2928, 2855, 1702, 1255,. 1072, 837' H-NMR (CDCl-U); δ 0 (SH, s), 0.85 (9H, sj, 1 2.02 (2H„ m), 2.5 (1H UV (EtOH); 205 square meters; hb2S; *70.4 (0=1,.1., m), 4.35 (1H, m), 8.81 EtOH). cm'1: .45 (1.H, mj, 1.78 (3H, (1H, s) ppm; (2S,3aS.4aS}-2-tert-butylphenyloxy-3a-carbamoyl-bis(4-hydroxy- a) M-ethyl-(1: R, 3 S,5 R >-3-acetoxy-5-(4-b-rhambensisosulfoniioxyleikSobexncarboxylate ((2.4.b)) compound (R=H, L=OBros, A=COOCHJ); Starting from compound (2.A) (R~H) (1.4 g, 6.47 moles) and 4-bromobenzenesulfonyl sulfone (4.22 g, 18.19 moles), the procedure for compound (2.4.a) (R~H, :L=OTosj) is followed. Thus, compound (2.4.b) is obtained in the form of white crystals. (RH, t~öBros, A=CÖÖOH3) <2.6 g, 96%; . Op.; 110-1115C: IR 2958, 1734, 13-63, 1246. 1188, 822, 742 cm''; 1H-NMR (500 MHz, CDClIS); S 7.76 (2H, d, 4=8.6Hz), 7.70 (2H, d, 4=8.6Hz), 4.88 (1H, dddtí, 4 = 11.6, 11.6, 4.37, 4.37Hz), 4.46 (1H, ddbd, 11.6, 11.6, 4.8: 4.6Hz.),. 3.69 (3H-, s), 2.37 (1H:. m}·., 2.28 (2H, ro), 2.02 (3H, s), 1.58 (2H, m), 1.3S (1H< dd., 4=24.0, 12.4Hz) pp-m; MS (m / 2): 419 <M\ 1), 405 (1), 363 (3). 221 (10). 157 (34J, 138 (70). 107 (15), 79 (68); jabJÍ: -10.55 (¢=1.50, GH-CI's). b) Methyl-(1R, 3S, 5'R')-§(4-bForobenzo'lsulphnoxy)-3hydroxyctohexanecarboxylate |(2.5,:b) or five (R=H, L=OSros, A = COOCHs)j Starting from compound (2.4.5) (R=H, L=0-Sros, A=COQCH3) (2.55 g, 6.08 mmol), we proceed as described for compound (2.5.a) (R=H. L=OTos). Thus, we obtain compound (2.5.b) (R=H, t^OBros, A=CO'Ö-CH3) in the form of white crystals (2.25 g, 98%), M.p.: 95-98°C; !R (film): 3397, 2954, 1734, 1396, 1186, 815, 740 cm''; 1H NMR (500 MHz, CQCH); 8 7.76 (2H, d, 4=8.8Hz), 7.70 (2H, d, J=8.8Hz)-, 4.48 (1H, dddd. 4=11.5, 11.5, 4..5., 4.5Hz), 3.88 (3H. s), 3.6-4 (1H, m), 2.28 (4H, m), 1.60 (1H, dd, 4=24.2, 12.5Hz), 1.48 (1H, db, 4=23.0, 11.5 Hz), 1.35 (1H, dd, 4=23.8, 12.5Hz) p;pm; MS (ro / z): 377 (Wli), 328 (3), 235 (10), 221 (13), 156 (85). 1Í3 (100), 97 (52), 79 (53); ( 0=1.48, CHCIsi $· e> M.ethyl-(1R ,3 R,5 R) - 3-benzoyl-oxy~5~(4-brbrabenzeneS2uIfe nll oxl)clkiohexanecarboxylate [(2,6..b) vegyötet (R~H, l-OBros, Aí~COOCH3) A (2.5.b) vegyOletböl (R~H, L-OSros. A^COOGKa) kiindulva (1.15 g< 3:.05 mraol) a (2.6.a) vegyüietnél (R~H, L=öTes, A-COOCHy) leírtak szerint járunk el. Kitermelés' 1.13 g (73%):. Op.: 131-133 *C; Iceland (film); 3420, 2948. 1?17, 1362, 1180, 617, 737 cm'l 'H-RMR (500 MHz, CDCIS); § 7.35 (2H, d, J=7.4Kz.}, 7.72 (2H, d, 4« 8.5Hz), 7.60 (1K, t. 3=7.4 Hz), 7.56 (2R, d, 3=8.5 Hz), 7.49 (2H. t, 7.7Hz), 5.48 (1H, m), 4.-81 (1H. dddd, 3 = 11..3, 11.3, 4.4, 4.4Hz), 2.85 (1H, dddd, J = 12.5, 12.5, 3.7, 3.7Hz). 2.47 (1H, m), 2.20 (2H, ra), 1.73 (3H, m) ppm, MS (m / z): 487 <M*. 1). 391 (4), 377 (10)., 260 (100), 23? (8), 221 (25); [a) 8i5; -59.32 (c=1.?S, CHCU). d) Compound I-(1R, 3-R, 5R)-5-(4-Prom benzoisoulfo η yloxy)-3 hydroxyequiohexanecarboxyl ((2.7,b) compound (R=H, l=OBros, A=COOCH3)) Starting from the compound (2.6.b) (R=H, L-OBros, A=COOCH3) (240 mg, 0.483 mmol), we proceed as described for the desired compound (2.7.a) (R=H, L=OTos, A~COöCH3). Yield: 167 mg (68 %). Op.: 107-108 *C. IR (film); 3527, 2954, 1732, 1577, 1365, 1187, S4Q, 618 cm'\ 'H-NMR (500 MHz, GDCS'): 5 7.78 (2H, d, 3=8.SHz), 7.70 (2H, d, 08.6Hz), 4.87 (1H, dddd, 3 = 10.9. 13.8, 4.5, 4.5 Hz), 4.31 (1H, m), 3.69 (3H, 5), 2.86 (1B, dddd, 3«· 12.1, 12.1, 3.7, 3.7 Hz), 2.24 (1H, d, 3®12.7Hz), 2.04 (1H. d, 3 = 11.7Hz), 1.94 (1H, d, 3=14.ÖHz), 1.65 (3H, m) ppm; MS (m / z): 394 <W* + 1S1), 295 (2), 221 (4), 157 (11), 97 (10); [a) c2S; -38.75 (c=ö.80, CHCl 3 ). e) Methyl 1-(1 R,3R,5R)-5-(4-bromobenzenesulfonoxy)-3-tert-butyldiphenylcyclohexanecarboxylate [(2.8,b) compound (RH, L=O8ros, P-T8DPS, A=COOCH3)] A. Starting from compound (2.7.6) (R=H, L^ÖSros, A=COOCH3) (299 rag,. 0.750 mmol) the same procedure as for compound (2.8.a) (R~H, L-öTos, P=T8ORS, Á»COOCK3) is followed. Thus we obtain compound (2.8.b) (R~H, L=O8res. P=TBDPS, A-CQöCHj) in the form of a viscous form (198 rag, 93 %), IR (film): 2955, 1738, 1577, 1472, 1370, 1180, 947, 821, 703 cm”; 'H-HMR (500 MHz, CDCis); 8 7.71 (2H, d, 3 = 8.8Hz), 7.34-7.60 (12H, ra), 4.6? (1H, ra), 4.17 (1H. bs), 3.78 (3H, m), 2.98 (1H, dddd, = 9.1. 9.1, 3.5, 3.5 Hz), 2.39 (1H, d, J-tí,9Hzj, 1.89 (1H, d, 3-13.9Hz), 1.79 (1H, d, 4=12.3Ηζ). 1.33 (1H, m>, 1.34 (2H, m), 1.02 (9H„ s), 0.91 (SR, s) ppm: MS (m / z): 599 (M\1), 419 (28). 337 (34), 293 (8), 199 (48), 139, (100), 107 (50), 79 (72); M / s: + 1.49 (c=1.75·, CHCl 5 ). f) .{2S,,3aS.4aS)-2-íe?c~fcuti-ídí(enUsylhoxy-3a-ksrbometöX'i~ bibíkíkío[3.1 .Ojhexár [(lb4) chemical (RH, P=TSDPS, A=COOCHa)j Proceeding as described for compound (t,b,1) (RH, R=78DM8, A=CÜÖCRS), compound (2.8 b) (R=H, L=08ros, P=T8DPS, A=COOCRS) (206 mg, 0.344 mmol) was converted into compound (1.b.4) (RR, P=7BDMS, A~CÖOCHS) to obtain a colorless solid (79 mg, 76%). IR (nim): 2952, 1725, 1428, 1113, 703 cm'1; H-HMR (500 MHz, CDC13): 6 7.64 (4H, dd, 4=6.20, 6.2GHz)·,. 7,357.45 (SR, m), 3.89 (ÍR, dddd, 4-7.7, 7.7, 7.7, 7.7Hz), 3.65 (3H, s), 2.28 (ÍR, dd, 4 = 12.9, 8.2 Hz), 2.12 (1H, dd, 4 = 12.3, 7.1Hz), 1.91 (2H, m), 1.77 (ÍR, ddd, 4-8.6, 5.0, 5.0Hz), 1.19 (1H, dd, 4=8.6, 4.8Hz), 1.02 (OH, s), 0.44 (1H, dd, 4=5.1. '5.1Hz) ppm; MS (m / z); 394 (M\ 1), 383 (4), 337 (65), 259 (3), 213 (100), 199 (20), 135 (18), 77(21): pain25: -73J4 (o= 1.75, CRCR). .1.11.:......Example (2S,3a8.,4aS)'2-tert-buts'idsphenHsz?iií.OXí-3a-(bidFöXlmetíi)btctkfofS.l.ölbekán 1(1.b.5) compound (R=H, P=TBDPS, A=CR2OH)j Starting from compound (lb4) (R=H, P=T8DPS, A=COOCH3) (189 mg, 1.253 mol), the procedure is as described for compounds (i,b.2) (R=H, P=TBOMS, A.=CH2OH). Purification is carried out by flash chromatography on silica gel (eluent; isooctane / ethyl acetate - 83:17) to give compound (i.b.5) (R=H. P=T8DPS, A=CR;,QH) as a viscous oil. (240 mg, 96). IR (film): 3322, 2932, 1428, 1113, 702 cm-1; 1H-NMR (500 MHZ, COCI3): § 7.76 (4R, mj, 7.58 (6R, m>, 3.97 (1 H, dddd, 4 = 7.1, 7.1, 7.1, 7.1 Hz), 3.56 (2H, bs), 1.84-2.05 (3H, m)„ 1.12 (1Ή, m), 1.03 (9H, s), 0.34 (1H, dd, 4=7.8, 5.4Hzj, 0.13 (ÍR, dd, 4=4.6, 4.6 Hz) ppm; MS (m / z): 365 (M*-1, 1), 291 (3), 231 (10), 199 (100), 181 (12), 139 (27), 93 (77), 79 (24), [aj / 6: -25.74 (0=2.16, CHCR). (.2S,3.aS,4aS.)-2-tert-butyldiphenylsilyloxy-3a-formylcyclo[3.1.Ojhexane {(1,b.8) compound (R=H, P=T8QPS, A=CHO)f Starting from compound (lbS) (R=H, P-TBOPS, A«CH2OH) (230 mg, 0.627 ppm), the procedure is as described for compound (ib,3) (R«H, P=78DMS, A«CHO). Thus, 210 mg (92%) (yield) of compound (R=H, P=TBDPS, A-CHOl) is obtained. IR (film): 3439, 3061, 2954, 2858, 1704, 1589, 1471, 1 111, 1036, 823.703 cm*'': 'W-RMR (SCO MHz, CDCia): S 8.85 (1H, s), 7.68-7.69 <4H, m), 3.99 (ÍH, q, J=7.4Hz>, 2.30 (1H, dd, 3=13.1, 8.0Hz), 2.03-1.98 (2H, m), 1.931.87 (2H, m>). 1.22 <1H, dd, J=S.4, 6.0Hz), 1.02 (9H, s), 0.74 <1H, dd, J5.3, 5.3Hz) ppm; {a}ozs: -90.00 (c = 1.00, CHCl 3 ). (2Sl3aS,4aS)-2-tert-buli:ldítenils'Zillőx'i-3a-eiinyl-blcikío{3.1 .Qlhexár; ((= b.7) compound (R~H, P=78DPS, A=C-CH}j (MeO}jP(O}CHN2 (188 mg, 1.263 mmol) in THP (3 ml) cooled to -78 °C was added dropwise t-SuOK solution (1.26 ml, 1.28 mmol, 1.0 M solution prepared in TRF). The mixture was stirred for 20 min at -78 °C until the yellow color remained. A solution of (tb.6) compound (RH, P-TBDPS, A=CHö) (389 mg, 1.043 mmol) in THF (3 ml) was added slowly, and the mixture was stirred overnight, then the temperature was allowed to rise naturally from -78 °C to room temperature. The reaction was quenched with water (10 ml) and The reaction was quenched by addition of Et2O (20 ml) and the organic phase was separated, the aqueous layer was extracted with Et2O (3x50 ml) and dried over MgSO4. The residue was separated by HPLC (hexadecyl acetate = 96:4) to give (1.5.7) (R=H, P=TBDPS, A=CsCH) as a colorless oil (338 mg, 9039). IRISH (film): 3291, 3071 14, 741 er'. 1932. 2143, 1530, 1473, 1428, 1114. 1091, •:H-NMR (500 MHz.,. CDC)3): δ 7.61-7.83 (4H, m), 7.34-7.43 (8H, m), 3.81 (1H, q, >7.6Hz), 2.18 (1H, dd, 3=12.5, 7.13Hz). 2.02 (1H, .ddd, 3=32.5, 8.1, 0.9Hz), 1.95 (1H, m). 1.93 (1H, sj, 1.56 (1H, m>, 1.92 (9H, s), 0.70 (1H, dd, 4 = 8.3, 0.1Hz), 0.31 (ÍH, t, J«6.0Hz> ppm; (ajo·25: -86.30 (οΜ,Οϋ, CHCls). (2S',3aR.,4aR)-2-tert-butyldiphenylsilyloxy-3a-carbomethoxybicyclo[3.1.0]hexane {(Compound Lf.4j {RH, P=TBDPS, A=CQÖCM3}, a) MeW-(1R,3R,5Sj-3-tertero-butHdiphenylsilyloxy-5-hydroxy-cyclohexanecarboxylate ((3.8.b) compound (R=HSP=7BDPS, A«COOCHs)j Starting from compound (2.A) (R«H, A=COGCH3) and TSDPSCi, via compound (3.7,b) (R=H, P=TBDPS, A=COOCHs), we proceed as described in example 4 with compound (3.6.a) (RH, P=7BDMS, A=COOCHS). Thus, we obtain the title compound in the form of a viscous oil. The yield calculated for the two steps is 92%. IRL {film): 34-84, 2952, 1738, 1:428. 1112. 1049; 307, 710 cm*'; 'H-IWR (500 MHz, CDCl3): δ 7.65 (4R, m), 7.40 (6H, m), 3.δδ <3H; Sj, 3.60 (1H, tiddd, 4=0.9., 18.9, 4.3, 4.3 Hz), 3.41 (1H, m), 2.17 (4H, m), I, 30 (1H, dd, 1=12.8, 12.6 Hz), 1.41 (WjÖ, 3=5.2Hz), 1.34 (3H, m) ppm; MS (m / z): 412 (M+, 7), 355 (5), 323 (57), 198 (100). 153 (37), 105 (21), 78 (85), 1.02 S: -16.44 (c=1.60, CHCR). b) Methyl-Cl:S,3R<5S}~3-f«.te-butyldiphenylS2'!lif'O'xi-S~tö'Zi:oxycyclohexanecarboxylate ((3.5.d) compound (R=H, L=OTos, P=T8DPS, A=COOCH3)| Starting from compound (3.8.0) (R=H, P=T80PS, A=COOCH3), we proceed as described for compound (2.4.a) (R=H, 1=0Toa, A=COOCHS). Thus, we obtain compound (3.8,b) in the form of a viscous oil, with a yield of 94%. IR (film)·;. 2955. 1733, 1353, 1178, 1171.824,704 cm*': 1H-NMR (500 MHz, COCl 2 ): S 7.89 (2H, d, 1=8.3Kz). 7.58 (4H, m), 7.28 (2H; d, 3 = 8.1 Hz), 4.18 (1H, dddd, 1=11.6, 11..6,. 4.6, 4.6 Hz) 3.62 (3H; s), 3.48 (ÍR, dddd, 1=11.1. 77.1; 4.1, 4.1 Hz), 2.47 (3Η, s), 2.15-1.98 (4H, m), 1.52 (1H, ddd, 1=5.6, 5.57, 5.6Hz), 7.42 (1H, ddd.. 1 = 12.0, 72.0, 12.0Hz), 0.28 (9H, s) ppm; MS- (m / z): 557 (Μ*, 1), SOS -(9)., 461 (1), 363 (49), 337 (67), 283 (38), 213 (47), 139 (32), 97 (100), 78 (77); (ajD25: +2.38 (C=1;77, CHCl:3). c) (2S,3aR,4aR)-2~tere.-uti'ldrf-entisilyloxy-3.a~carbornetexiblc:cyclo(3',1.0jbexane f(lf,4) compound (R=H, P=T8DPS·, A=COOCH3)) The compound (3.6.b) (R=H, l=O8rss, P=T8DPS, A=COO€H-.S·) was isolated from the compound (lb1) (R=H, P=TBDMS, A=CGGCR3>) as described above. The yield was 81%. IR (film): 3287, 2834, 1732, 1457, 1281, 1017 cm*4; ÍH-HMR (500 MHz, CDCIte: 6 3.73 (2H, m), 3.72 (3H; s), 2.53 (7H, dddd, «1=12.2, 12.2, 3.4, 3.4 Hz), 2.28 (ÍR, d, J = 11s3Hz), 2.17 (2H, d, 3=17.7Hz), 1.30 (2H, ddd, 1=12.0, 12.0, 12.0 Hz), 1.23 (1 H, ddd, 1 = 11.4 II, 4, 11.4 Hz) ppm; MS (m / z); 394 <M\ 1),. 337 (.31)., 268 (5), 799 (55), 153 (48), 10? (100), 79 (52); (ajc2:s·. + 31,87 (¢=1,71..CHCij). 15. példa f2:Ss3aR.(4eR')-2-terc-but!'.!difenllszlli:lox'i-'3a- <bidroximetil)bícIkioíS.l.Ojhexán ((!,?,5) vegyölet(R=H, P=T8DPS, A=CH2OH), Az. (1.14) vegyöletből <R=H, P=TSDPS, A=COOCHs) a íl.b.2) vegyöleinél (R=H, P-T8DMS, A=CR£OH) leírtak szerint járunk sí. így kapjuk a (2S.,3aR,4aR)-2-terc-butildiíen:iisziilioxi-3a-(hid roximefll)blclklö[3.1 .öjhexánt HU.5} vegyület 0R=H, P=TBDPS, A=CH2OH> 98%os kitermeléssel. m (film): 3332, 2931, 1426, 1111, 1008, 822, 702 cm·; 1H~NMR (500 MHz, CDC!3}-: S 7.82 (4R, dd, 4-7.9, 7.5Hz), 7.39 (6H, m), 4.37 (1H, t, 4=6.27Hz), 3.57 (2H; s), 1.90-2.02 (3R, m), 1.80 (IR, d. J=13.8.Hz), 1.21 (1H, t 4=4.1Hz), 1.15 (ÍR, ra), 1.03 (SH, s), 0.80 (1H, m) ppm. VIS (m / z): 365 1, 7), 291 (6), 231 (17), 199 (100), 181 (17), 139 5), 93 (79), 79 (16); (V5: +5.56 (c=1.5, GHCU). Example 19 (SS.SaR^aRj-S-tert-butylphenylsilyloxy-S-formobicic-ic:ío[3.1.0jhexane [(116) desired (R=R, P=TBDPS, A=CRO)] Starting from the compound (1.1-5) (R=H, P=TBDFS, A=CH2OH), we proceed as described for the compounds (1b-,3) (R=H, P=T8DMS, A-CHO). The yield is 95%. IRISH (film): 2955, 1704, 1590, 1472, 1426, 1112, 1072, 822, 702 cm!; 1H-NMR (500 MHz, COCl 3 ): δ 8.85 (1H, s), 7.67 (4R, m). 7.43 (2H, dl, J-7.0, 1.0Hz), 7.37 (4H, dt, 4 = 7.0, 1.0Hz), 4.40 (1H, t, 4=6.ORz). 2.39 (1H, dd< 4 = 14, 6.0 Hz), 1.69 (ÍR, d, 4=13.0Hz), 1.86 (1H, -d, 4=14.ORz), 7.53 (1R, m), 1.04 (SR, s) ppm; [a]»®5: +34.4 (¢=1.6, CHCl 3 ). (2S,3aR,4aR)~2-terc-butfidi?en!iszíÍ!loxi-3a-eOnll-bicikiQ[3,1 .Ojhexán [(1.17) vagyóiét (RH, R=TBDPS, A=C«CH)] Az (if5) vsgületbbl (R=R. PUBDPS, A=CRO) kiindulva az (tb.7) vegjölelnél (.R=-H, R=T8DMS, A=CsCH) leírtak szerint, járunk el A kitermelés 88%~os, IR (film): 3310 (s), 1.378, 1362, 1299, 1282 707 cm'1: 3071, 2931, 2857,. 2113, 1530, 1472, 1428, 1234, 1196, 1713, 1026, 933, 913, 855, 522, 'H-NMR (500 MHz. CDCh): δ 7.50 (4R, m, 7,2,2,2, R 8Hz), 7.37 (4H, td, 4=1.8Hz), 4.32 (1H, m), 2.06 (2H, m), 2.04 (1H, dl, 4=6, 74Hz), 7.90 (7H, S), 1.50 (1H, d, 4 = 14H, Η, 5, Η l 5.70Hz), 7.49 (IR, i, J = 5Hz), 1.03 (9H, s), 1.03 (1H., m), Í«U£S; +21.4 (¢=1.2, CRCI-j). (2R!3eC,4aC)-2-tere-butyldifsmiszi1iicx!-3:a~carbomethox!biciquio[3..1.qh:exane [(La.4} veguyle (R='H, P-TBD-FS, A«C0OCWs) (a) In M = t11- (1R, 3 C, 5 R) - 3 rc - bu 1 Π d I fe η H sz 1 ii i ο xi - § ~1 ο zi le x-í dicyohexane carboxylate |(2.3.b) vegulet (R = H, L~OTos. P = TCODRS, A-TCODRS, ATCOD8] A (2.5.8) vegüieíbői (R=H, L~OTos, Á=COOCK3) kiindulva a (2.8.S) vegyutetnéi (R=H, L«OTos, P«T;8:DMS, A=COOCH3) leírtak szerint tărunk el. A kitermelés 91%.-es. ÍR (film): 2832, 2857, 1736, 1428, 1364, 1177, 1107, 928, 822, 701 boa cm ^H-HMR (508 MHz, CDCI3): δ 7.88 <2H, d, 3.8 = Hz, 37.7. dm, J=7Hz), 7.44 (2H, q, 3=7Hz), 7.38 (4R, í, 3-SHz}, 7.2δ (2H, d, 3=8.4Hz), 4.16 (1H, tt, 3=4. 12Hz), 3.83 (3H, s), 3.4 (3H, 3=4). 11 Hz)., 2.43 (3H, s), 2.13 (1H, dm, 3=12Hz), 1.00 (SH, s) ppm; ia]:;;2S: -3.07 (c=1.04, CHCI3). b) (2 R, 3 a S, 4 a $)- 2 - te re - bu ti ! defined is z 11 Η οx 1- 3 a - ka rb eme to xi bíeikio[3.1 .OJhexán [fi.a.4) vegulet (R = H, P=TBDPS, A=COOCH3)I Starting from compound (2.3.b) (R«H„ t=QTos;P= TSQPS, A-COOCH3), we proceed as described for compound (í,b.1) (R=H, F»TBOMS, A=COOCH3). The yield is 75%. IR (film): 2932. 2857, 1723, 1589, 1472, 1428, 1297, 1148, 11 12, 1088, 702 em: H-NMR (500 MHz, CDCIS): 3 7.61 (4H, tid, 3 = 1, 7Hz), 7.42 (2H, 1, = 7Hz). 7.37 (4H, t, J=7Hz), 4.36 (ÍH, t, 6.1Hz), . 3.63 (3H, s), 2.37 (1H, ddd, 3 = 1, 5.4, 14 Hz), 1.99 (1H, d, J = 14Hz), 1.98 (1H, tid, 0=6, 14Hz), 1.87 (1H. dt, 3 = 5, 9Hz), 1.82 (1H, d, J=14Hz), 1.63 (1 H, tí, 3=4, 6Hz), 1.50 (TH, dm, 3=9Hz), 1.03 (8H, s) ppm; [«b3S; -38.8 (c = 0.46, CHCl 5 ). Example 22 (.2R,3a.S,.4a'S)-2-tert-butyldiphenylsulfide Hloxl-3a- <hldroximetil)fcieiklo[3.1 .Ojbexán Hi.a.5) vegyület (R=K;P=TBÖP8< A=CH5OH)j From the compound (1.a.4) (R=H, P=T80PS, A=COOCH3) we proceed as described for the compound (1b2) (R=H, P=T8DMS, A~CH2OH). The product is obtained in quantitative yield. IR (film:): 3348, 2930, 1589, 1472, 1428, 1111. 1092, 1078, 1031, 822.701 cm'!; 'R-NME (500 MHz, CDCIS): S 7.26 (4H„ dd, 3=1, 7Hz), 7.41 (2R, t, 3=7Hz), 7.38 (4H, t, 3=7Hz); 4.38 (1H, I, 3=8.3Hz), 3.57 (2H, s), 2.00 (1H, dd, 3=6, 13Hz), 1.65 < 1H, dd, 3=7, 14Hz), 1.92 (1Η, d, 3 = 14Hz), 1.80 (1H, tid. =14Hz), 1.22 (2H< m), 1.15 (1H, m>, 1.04 (9H, s); 0.60 (1H, ml ppm; (ab25: -5,6 (¢=1.7, CHCM (2R<3aS,4aS)-2-tert-PuUtdifenHs2i iiiíexi-Sa-fcrmil· b:ieiklap.1.0jbe.xán «Ia6) compound (R=H, P=TSDPS, A=CHO)j Starting from compound (La.5) (R=H, P=TBDPS, A=CHSOH), the compound (lb3) (R=H. P-TBDMS, A>CHO>) is prepared as described. The yield is 93%. IR (film): 2331, 1701, 1588, 1472, 1195, 1008, 322, 702 cm'; 'R-NMR (505 MHz, GD€I3): § 3, SS ('H, s), 7.61 (4H, m), 7.43 (2H, t, •j=7Bz),7.3? (4H,:t, 4.41 (1H, t, J=6Hz), 2.39 (1H, dd, 3 = 6:. 14Hz), 1.04 (8R, s) ppm.; 24. eéid [ab : «35.3 (¢=1.8, CHCIS). (2 R, 3 a R, 4a R) -2 - í e re -b uí í;id if e η II sz 11 ite xi - 3 a - ka rbo m eto x I feicíkie[3.1.0bexán [(),h.4) vegyulet (R=H, P=TRDR$, A=COOCH3)j a) toé111-(1 C, 3C, 5C)-3-ter-buti IdIfeni.l-5-powderI1οx 1 Cíkiohexanecarboxylate [(3.13.8) vegulet {R = H, L=OTcs, P-TBDPS, A=COOCHs)j A (3.12) vehicle <R-H, L=OTos, A~C'OOCH3) (4,8 g, 4,53 -mmol) .kiindulva, a (2.8.a) vegyületnét (R=H. i=OTos, P=TBDFS„ A=COOCH3) leírtak szerint járunk el. A kitermelés 90%-es. IR (film): 2954, 1731, 1272, 1 176, 1107, 945, 813, 713, 664 crrí1; H-NMR (508 MHz, CDCb): δ 7.53-7.25 (14H, m), 4.84 (1H, m}, 3.68 (3H, s), 2.95 (1 H, dk 3=3.3, 12.?Hz), 2.45 (3H, s), 2.37 (1H, d, 3=12.4Bz), 1.84 (1H, d, 3=12.7Hz), MS (m / z): 566 (VT), 477, 431, 399, 353, 283, 225, 198, 139, 91 {alapcsúcs); [ab:25'; +7.82 (¢=1.31, CHCR). b) (2R,3aR,4aR)-2-erc-bethyldlphenyls iRloxy-3a-carbhemeth oxybicyclo[3.1.ohexane í(th.4) compound (R~H, P=TBOPS, A=COOCH3)1 Starting from compound (3.13.5) (F=R, P=TBDPS, A=COOCHS) (7.3 g, 12.89 mmol), the procedure for compound (lb1) (R=H, P=TBDMS, A=CÖQCH3) was followed. The yield was 79%, IR (film); 2952, 2858, 1723, 1428, 1370, 1219, 1112, 823, 741, 702 cm'; 1H-NMR (508 MHz, C&Cb); δ 7.65-7.38 (10H. m), 3.89 <1H, m), 3.δδ (3H, s), 2.12 (1H, m), 1.92 (2H, m), 1.77 (1H, m), 1.14 (2H, m), 1.02 (OH, s), 0.45 (1H.m) ppm; MS title: 394 (M*), 393 (M+-1), 853, 351, 337, 296, 259, 213 (primary), 183, 135, 105, 77. 25. [ab +72.58 (¢=1.08, CHCl3). {'2R,3sR,4aR)-2-tert-butyldiphenylphenyloxy-3:a-<hidro.ximetil > blcikíö[3.1 .Ojbexan «I h.5).compound <R=H, P=T8DPS, A=CH2GH)l Starting from compound (ib2) (R=H, P=T8DPS, A=COOCKS) <R=H, P=TRDMS We proceed as described for A=CHjOH). The yield is 88%. IR (film): 3327, 2828, 2856, 1470, 1426, 1276, 1112, 1087, 1030, 822, 730, 700 cm''; 'H-HMR (500 MHz, CDCis); δ 7.65-7.35 (1QH, m), 3.87 (1H, ddd, = 7.0, 7.2, 7.0), 3.55 (2H, bs). 2.04 (1H, m), . 1.93 (1H, m), 1.87 (2H, m), 1.39 (1H, m), 1.02 (SH, s), 0.45 (1H, m), 0.13 (1H, fn> ppm; MS (m / z): 365 (M'-l), 322, 281, 237, 188 (aia peak), 181, 138:, 99, 77; falc*8: +24.7? (c=1.18, CHCH 2 ). Compound 2&_gei.S5 (2R,3.aR,4aR)-2-tert~butyl::cltphenysilyloxy~3.a-fofmilbicfkioj3.1..üjhexá.rs í(Lb.S) (R=H, P=T8GPS, A=C:HO)j Starting from compound (ib3): (R=H, P=TBDPS, A=CHSOH) we proceed as described for compound (ib3) (R=H, P=TBDMS, A=CHG). IR (film): 2031, 2857, 1708, 1472, 1338, 1362, 1200, 1113, 1093, 1035, 901, 823, 742, 612 cm-1; H-NMR (500 MHz, COCl3): 3 8.8? (1H, s), 7.85-7.35 (10H, m), 3.98 (ΊΗ, m), 2.29 (ÍR, cd. 4 = 12.9, 8.1Hz), 2.01 (2H, m), t.8S (2H, m), 1.22 (1H, m), 1.02 (8R, s), 0.74 (1H, í, 4 = 5.4Hz) ppm; MS (m / z): 363. 332, 307 (wood pesúcs), 283, 277. 263, 229, 211, 199, 181, 151, 139, 121, 91, 77, 57, 41; (a) o 2 S: +91.49 (e=0.47, CHCl 3 ). (1 R,2S,3aS,4sS)-3a-carbamyl-2-tert-butyldiphenylsilyloxy~1 -methylbicyclo[3,1.0]hexane (11.a,7) compound (R=Me, P=7BDPS, A=COOCHs)j a) Methyl-yl (S,3S,4R,5R)-3-tert-butyldiphenyl2-yloxy-4-methyl-5-acetoxycyclohexanecarboxylate [(2.1.c) compound (R=Me, P=TSDPS, A=CGOCH3)] Compound (2713) (R=Me, A=COOGH5) (0.81 g, 3.52 mmol), imidazol-1 (0.72 g, 10.57 99 %) and DMAP (4-dimethylaminopyridine; 22 mg) in dry DMF (15 ml) were mixed to prepare TBDPSCI (1.8 ml, 7.04 mol, 98%) was added dropwise. The mixture was stirred for 20 h at room temperature. After the reaction was complete, the reaction mixture was poured into a mixture of water / ethyl acetate (80 ml). The organic layer was separated and the aqueous layer was extracted with ethyl acetate (3x50 ml). The combined extracts were washed with NaCl (3x10 ml), dried over MgSO4 and concentrated. The residue was separated by HPLC (eluent: isooctane / ethyl acetate - 9:1) to give compound (12.1c) (R=Me, P=TBOPS. A=COOCH3) (1.34 g, 84%). [ajo = >,S (CHC13, c = 0.65} H-NMR [500 MHz, CDCIS, ppm): 7.85-7.35 (10H, m), 4.59 (1H, 5, >12.4, 4.5 Hz), 3.72 (1H, m), 3.62 (3H, s), 2.26 pH, m), 2.09 (1H, m), 2.02 (3H, s), 1.81 (1K, dt, 3=12.6, 4.1 Hz), 1.61 (1H, m). 1.08 (10H, s), 1.05 (3H, d, 3=6.4 Hz}, IR (film): 2954, 1737, 1428, 1354, 1239, 1111, 1037, 322, 740, 702 cm'1: MS (m / z): 411 (&Γ-57), 38S, 351, 317, 2S1. 259, 258, 241, 195, 181, 135, 121, 93. 43 {eiapcchcs}. bs Methyl-1S,3S,4R,5R}-3-tert-butyl(enylsinyl-4-methyl-5-butyroxycyclohexanecarboxylate ?(2.2.c) compound (R=Me, P=TBDPS, A=COOCH.5}| Compound (2.1,c) (R=Ms, P^TBOPS, A=CGOCH3) (392 mg, 0.892 mmol). A portion of dry K2CO3 (30 mg) was suspended in 10 ml of dry MeOH at room temperature. After 10 min, a second portion of K2CO3 (19 mg) was added (total amount: 49 mg, 0.496 mmol). The mixture was stirred for 6 h and then poured into a mixture of water and Et2O (70 ml: 50 ml). The organic layer was separated and the aqueous layer was extracted with diethyl ether (3x50 ml) and dried over MgSO4. Flash chromatography on silica gel (eluent; Isooctane / ethyl acetate = 9:1) gave the hydroxy compound (2.2 o) (R«Me, P=T8DPS, A=COÖCH3) as a colorless oil (344 mg, 98%). IR(film); 3446, 2954, 2856, 7737, 1654, 1472, 1362, 1279, 1240, 1173, 7008, 852, 822, 795, 741, 702, 611 cm'1*H«NMR (500 MHz, C0CI5, ppm: 7.65 (4H, m), 7.44 (2H, m), 7.37 (4H, m). 3.69 (1H, m), 3.64 (3H, s), 3.57 <7 H, m), 2.16 (1H, m), 2.08 (1H, m), 1.77 (1H, öt, 3=72.6, 4.7 Hz), 1.69 (2H, t, 3=8.9 Hz), 1.56 (ÍR, q, 3 = 12.4 Hz), 1.37 (1H, d, >5.3 Hz), 7.06 (9H, s), 1.02 (3H, d, 3=7.0 Hz), MS (m / z): 337 (7), 309 (5), 291 (35), 193 (700), 166 (85), 181 (17) 153 (34), 121 (23), 93 (68), 57 (47); Í«I©2:8·. *33,0 (0=0,54, GHCIj). c) Metii-{tS%.3S,4'R,5'R}-3~terc-butlldtfenllszilHoxí-4-metil-5-tozlloxleiklöhexán-karboxflát ((2.3.0) vegyüieí (R=Me, P=TBDPS, L«OTos, A=COOCH3)j (2.2,c) vegyűlet (R=Me, mm cl), p -1 o fa o Is za I f ο η II - k tor ld P=TBDMS, A-COOCHs) (278 mg, 0.828 (323 mg, 1.69 mmol, 98 %}, DMAR (6.7 mg, 0.042 mmol) in 10 ml dry CH2Cl2 was added at 0 °C (ice bath) to Et3N (388 μξ 2.54 mmol). The mixture was refluxed for 3 days, then p-toluenesulfonyl chloride (320 mg, 1.69 mmol, 93 %), DMAP4 (5.1 mg, 0.042 mmol) and Et3H (500 μl) were added. The resulting solution was refluxed for 2 days, then p-toluenesulfonyl chloride (3-20 mg, 1.66 mmol, 98 %), DMAP (5.1 mg, 0.042 mmol) and Et3N (800 µl) are added, and refluxing is continued for another 1 day. The resulting mixture is diluted with 20 ml of dichloromethane, washed with NaCl solution, and the aqueous phase is extracted with ethyl acetate (4 x 50 ml). The combined organic phases are dried over MgSO4. The solution is filtered, concentrated and subjected to column chromatography on silica gel (eluent isooctane / ethyl acetate = 9:1). Thus, we obtain the compound (2.3.c) P=TBDPS, L=ÖTos, A-CQQCH3) (316 mg, 83.5%) világos-sárga olajájában. ÍR (film): 2954, 2888, 1737, 1365, 12:46, 1177. 1 106, 955, 704, 867 cm':; 'H-NMR (500 MHz, CDCIj, ppm): 7.71: <2H, d, 9=8.3 Hz), 7.58 (4H, m), 7.43 (2H, m).. 7.37 (4H, m), 7.31 (2H, d, 3=8.1 Hz), 4.27 (1H, dt., 3-12.0, 4.7 Hz), 3.61 <3H, s), 3.57 (1H, ddö, 3^0.6, 5.1, 4.8 Hz), 2.45 (3H.s), 2.17 (1H, m), 2.01 (1H, m)„ 1.81 (1H, dt, 4=12.8, 4.2 Hz). 1,74 (1H, dd, 3 = 1:2.6 Hz), 1.64 (2H, m), 1.02 (9H, s), 0.99 <3H, d, 4=6.6 Hz); MS (ffl / z): 523 (25). 507 (1), 463 (1), 409 (3), 353 (94), 307 (20), 293 (18), 213 (30), 199 (3:2), 1:35 (35), 91 (100), 77 (38); fcfo*5: »10.0 (c=1,22, CHC«) d) < 1 R,2S,3sS,4sS)-33~karbomefoxi-2-terc-öufif£lifenlíszinioxMmetíl-bicfkl:o{3.1,0]bexán ((la7) vegyüiet (R-Me, P=TBDPS, A-COOCH;.)) To a solution of the tosifate compound (2.3.c) (R=Ms, P=TBDPS, L=OTos, A=COOCHa) (245 mg, 0.415 mmol) in a mixture of tert-BuOH (5 ml) and THF (2.8 ml) at 45 °C was added tert-8uOK (540 µl· Q„54 mmol, 1 M solution in tert-S-uOH). The mixture was stirred at 45 °C for 1.5 h, then poured into a mixture of water and ethyl acetate (190 ml; 50 ml). The organic phase was separated and the aqueous layer was extracted with ethyl acetate (3 x 50 ml), then dried over MgSO4. The residue was separated by flash chromatography (eluent: isooctane / ethyl acetate = 100 2) to obtain compound (ia7) (R=Me, P=T8DPS, A=COOCH3) (122 mg, 72.0%) as a colorless oil. IRISH (film): 2031, 1724, 1428, 1288, 1224, 1147, Ilii, 1073, 1015, 933, 822, 740, 702, SOS cm); H-NMR (500 MHz, COCi», ppm): 7.61 (14H, m), 7.42 (2H, m), 7.38 (4H, t, 3 = 7.2 Hz), 4.19 (1H, t, 3 = 6.0 Hz), 3.62 (3H, s), 2.30 (2H, m), 1.97 c (1 Η, d, 4 = 14.2 Hz), 1.85 (1 Η, ro), 1.64 (1Η, t, 4=4.6 Hz). 1.35 (1Η, dd, >6.7, 3.9 Hz), 1.89 (9Η, s), 0.99 (3H, d. 4=6.9Hz), MS (m / z); I«)e2S·. -13.2 (0=1.61, CHCU). Example 58 (1 R.2S,3aS,4aS)-3a~bidroxsmsdH2-tert-buti1diphenhszHH:exi~1~meth-b:icykilo(3.1..0jh-e-'xane ((La.8) compound (R=Me,. P=TBOPS, A=CH?ÖH)j To a solution of compound (La.7) (R-Me, P=T8DPS, A~COO€-H3) (136 mg, 0.33 mol) in tetrahydrofuran (15 ml) at 0 °C was added dropwise UAIH4 (0.85 mol, 0.55 mol, 1M solution in THF). The resulting mixture was stirred at this temperature for 1.5 h, then water (0.1 ml) was added. The mixture was filtered through cetyl ether and concentrated. The residue was purified by flash chromatography (silica gel, eluent; isooctane:acetate - 7:3) to give compound (La.-8) (R=Me, P-TBOPS, A=CH2OH) as an oil (124 mg, 97.8%). IR (film); 3420, 2930, 1427, 11 11, 1078, 1014, 701, 61 1, 504 cm1; 'H-HMR (500 MHZ, CDCI3, ppm); 7,53 (4Η, ro), 7,42 (2H, ro), 7,36 (4H, roj, 4,21 (1H, t, 4-6,8 Hz), 3,54 (1H, dd, 4 = 1,4, 5,6 Hz), 3,50 (1H, dd, 4=11,4, 5,5Hz), 2,29 (1H, m), 1,95 (1H, ddd, 4=13,7, 6,0, 1,4 Hz), 1,23 (1H, t, 4-4,12 Hz), 1,14 HH, m), 1,08 (SH, s), 0,99 (3H, cL 4=7,0 Hz), 0,41 (1H, dd, 4=8,4, 4,3 Hz), 0,80 (1H, ro),. MS (m / z): 381 (M**1„ 1), 363 (22). 337 (1), 323 (22), 305 (5), 285 (9), 287 (24), 245 (63), 225 (18), 199 (83), 179 (19), 153 (28). 139 (51), 107 (100), 91 (58), 79 (72), 57 (86), 41 (78); E«j0*s'. -2,6 (c=Ö,66, CHCh). 29. oéi dg (1 R,2S, 3aS.4aS )-3a-formfMerc:-buf|ídife-nits2ihio-xi-1 -roetifbscikjop. 1. To a solution of compound (La.9) (R=Me, R=TSDPS, A=CHO) (COCt)s (18 µl, 0.21 mol) in dichloromethane (1.5 ml) was added dropwise a solution of -78°C- warm to room temperature. The reaction was quenched by addition of cold water, the organic phase was separated, the aqueous layers were extracted with diethyl ether (3 x 50 ml) and dried over MgSO4. The residue was separated by HPIX (eluent: isoctane / ethyl acetate = 98:5) to give (1.3.9) (R=Me, P=T8DPS. A~CMÖ) as a colorless oil (30 mg, 7:5%). IR (Olm): 3420. 2930, 1427, 111 1, 1878, 1014, 701, 611, 584 cm'í; 'H-NMR (500 M Hz, CDC-h, ppm): 8:.,80 <1H,;s), 7.62 (4H, m), 7.42 (6H, m), 4.24 (1H, t, 3-5.S Hz),. 2..32 (1H, dd,:3=14.4, 8.1 Hz), í.96 (2H, m), 1.84 (1H, d, 3 = 14.4Hz), 1.38 (1H, m), 1.08 (OH, s), 1.00 (3H, d, 3=7.0 H, d., 3 = 14.4Hz). 6.8 Hz), MS (m / z): 378 (M*. í), 381 (4), 321 (100), 303 (10), 285 (10), 267 (24), 263 (18), 243 (74), 225 (39),. 199 (ISO), 183 (78), 165 (39), 139 (72), 135 (48), 195 (59), 91 (34), 77 (69), 87 (95), 41 (80), kh •16.2 (0=0.59, CHCM. 30. example (1 S.2P ,3aR,.4aR)-3a-carbam.etö'xi-2.-íetc«buíHdiiPhen)lszjlíif:oxt-1 -methylbicyclo(3.1 .Ojdexan [(if8) vegulet (R=Me, P=TOCHA)) a) Methii-(1'S}3S,4R,5R>-3-1oZ'íthoxy-4-methyl-5-aceloxl· csclohexenecarboxdate ((3.4.c) vegulet (R=M:e, L=OTos,. A=-COOCH3.)j: Starting from compound (2'.8) (R=Me, Z=Me, A»COOOH3.) (1.05 g, 4.57 mmol) we proceed as described for compound (2.3.c) (R=Me, R=T8DPS. L=O7os, A=CÖOCHa): el. The yield is 1.51 g (89 %}. IR (film): 2954, 1736, 1557, 1363, 1242, 1189. 1025, 956, S1S, 657 cm M-HMR (500 MHz, CDCf3, ppm): 7.6S (2H, d, 3 = 7.2 Hz), 7.36 (2H, d, 4 = 7.2 Hz), 4.74 (1H, dt, 3 = 12.2, 4.5 Hz), 4.49 (1H, dt, 3 = 12.1, 4.7 Hz), 3.59 (3H, dt, 3 = 12.1, 4.7 Hz). s), 2.46 (3H, s), 2.02 (3H, s), 1.98 (Í H, dt, 3 = 12.1, 4.7 Hz), 1.93 (1H, dl, 3 = 12.6, 4.6 Hz), 1.81 (2H, dd, 3=12.6 Hz), 1.63 (2H, dd, 3=12.8 Hz), 0.97 (3H, d, 3=6.9 Hz); MS (m / z): 384<M*> , 343, 326, 311, 300, 269, 258, 213, 170, 152, 111.93, 43 (a)peak); husband25= + 51.1 (0=0.59, CHCN), b) .Methyl-C1S,3S,4R,5R)-3-tosyloxy-4-methyl-5-hydroxycyclohexanecarboxylate [(3,5.c) compound (R=Me, L=OTos, A=CGÖCHs).l A (3.4.c) vegyűleibői kiindulva (R=Me, L=O7os, A=COGCH3) s (2..2.C) vegyuletnéi (R=Me, P=78D-PS, A=COOCHS) leírtak szerint jarunk el. A kitermelés· 80%, ÍR (film): 3439, 2888, 1732, 1439, 1353, 1176. 1:097,. 1021, 945, cm 'H-NMR (SCO MHz, COCI3, ppm): 7.78 (2H, d, 1=7.2 Hz), 7.32 (2H, d, 3 = 7.2 Hz), 4.52. (1H. dt, 4=10..8, 4.7 Hz). 3.69 (1H, m), 3.68 <3H, s), 2.45 (3H, s), 2.34 <1H, m), 2.25 (1H, m), 1.94 <2.H, m), 1.87 (1 H, dt, 4=13.2, 4.5 Hz), dd, 3=1 1.9 Hz), 0.91 (3H, ű, 3=7.0 Hz); MS (m / z): 340 (14^2), 295, £78, £47, 220, 194, 170, 155, 12? :sucs), 91, 87, 57; (a)02S: + 18.8 (¢=0.41, CHCH). * c; M et ί I - (1S, 3 S14 R, 5 R) - 3 -1 oz í I oxi -4 - met H · 5 - te -rc - b - ut H öt fe η H szi ίi i ο x 1 cyclohexene carboxylate |{3.ec) vegulet (R = Me, LTBDOS. A = COQCH3) Starting from compound (3.5.c) (R=Me. L=O7os, A-COOCHs), we proceed as described for compound (2.1.c) (R=Me,. P-TBDPS, A=COOCHS). The yield is 86 %, IR (film): 2855, 1736, 1598, 1427, 1383, 1177, 1031, 955, 814, 863, 820, 741, 703, 887 cm''; Κ-NMR (500 MHz, COCl3, ppm): 7.68-7.38 (14H, m), 4.27 (1H, dl, = 12.1, 4.8 Hz), 3.51 (3H, S), 3.56 (1H, m), 2.44 (3H, s), 2.17 (ÍR, m), 2.02 (1H, m), 1.83 (1 H, five,.4=12.5, 4.3 Hz), 1.73 (1H, tí, 3=12.7 Hz), 1.63 (2H, m), 1.01 (SH, s>, 0.99 (3H, d, 3=7.2 Hz); MS (m / z)·. 623 (M*-S7), . 463, 403, 353, 351, 293, 227, 213, 135, 91 (aiapcucs), 77; (aJ02:S: -2.6 (c«ö,S4·,CHCl1s) d) (1S, 2 R „ 3 a R, 4 a R) - 3 a - carb om et ο x I ~2 - te re - hdtüd If e η 1 í sz H i lo xi -1 meUí-bieiklo(3.1 .olhexane ((1.1.8)).compound (R=Me, P-TBDPS, A=COOCH3)} Starting from the compound (3.6.C) (R-Me, L=OTcs, P=TBDPS, A=COOCH3), we proceed as described for the compounds of (i.a.7) (R=Me, P=TBDPS, A=COOCH-3). The title compound is obtained as a colorless oil in 68% yield. IR (film): 2931, 2857. 1724, 1428, 1367, 1288, 1223, 1 147, 1111, 1073, 1015, 934, 822, 740, 702, 609 cm'\; 'H-NMR (500 MHz, CDCij, ppm): 7.62-7.31 (10H, m), 4.18 (1 H, t, 3=5.9 Hz), 3.59 (3H, s), 2.31 (2H, db, 3=13.7, 6.3 Hz), 1.96 (1 H, d, = 14.5 Hz), 1.84 (1 H, m), 1.64 (1H, t, 3 = 4.8 Hz), 1.35 (1 H. dd, 3 = 12.8, 5.9 Hz), 1.25 (1H, price,), 1.07 <9H, s), 0.99 (3H, d, 3=6.9 Hz), 0.91 (1H, ra), MS {rar'z}:. 408 í<), 3S1, 323, 273,213, 199, 153, 1.21 (tip), («b *13.9 (c=0.65, CHCIS). (1S, 2 R, 3 a R. 4 a R) - 3 a - hid re x I meti I -2 -í erc - bu 111 di le η ί I sí li I ox M - met II bícikío(3,1 .Ojbexane [(í.fS) compound (R=Me, P=TBDPS, A=CRyÖH)j Starting from compound (1f8) (R=Me, P=TBDPS, A=COOCH3), the procedure for compound (1.aS) (R = Me, P=TBDPS, a=CH2QK) is followed. The yield is 88%. IR (film): 3324, 2929, 2.857, 1554, 1471, 1427, 1363, 1194, 1107, 1078, 1011, 822, 740, 701, 610 cm'; 1H-NMR (SOO-MHz, CDCS 3 , ppm).; 7.68-7.37 (1ÖH. m), 4.21 (1H, L 3=8..0 Hz), 3.54 (1H, dd, d~1t.4, 6.0 Hz), 3.52 (1H. dd, 3 = 11.4, 8.0 Hz), 2.29 (1H. dd, 3 = 11.3, 8.1 Hz), 1.94 (1Η, dd, 3=14.6, 5.9 Hz), 1.86 (1H, d, 3=13.2 Hz), 1.23 (1H„ t, 3=4.1 Hz), 1.14 Í1H, m), 1.07 (9H, s), 0.99 (3H, d, 3=8.8 Hz), 8.8S (1H, m). 0.41 (dd, 3=8.1, 4.3 Hz); MS (m / 'Z)·. 323 (M*-57>, 308, 267, 245, 199, 181. 139, 107; [ab25: + 3.1 (¢=0.93. CHsCn. (1 S,2R<33:R,4aR3-3a-formH£”ter£;-butddiphenHszndoxÍ-1-phaetnbicikiop.l,Oyhexane [(Lf.lQ) chemical (R=Me, P=TBDPS, A=CHO)1 Starting from compound (1.9) (R=Me, P=TBDPS, A=CH2OH) we proceed as described for compound (1.8..9) (R=Me, P=TBDPS. A=CHO). The yield is 28%. [a)cIS: +15.8 (0=0.41, -GHsCi). 1H-NMR (500 MHz, CD€I3. ppm): 8.80 (1H, s), 7.61-7.35 (1OH, m), 4.24 (1H;t, 3 = 5.8 Hz), 2.31 (2H. m), 1.98 (1H, m, dd, 3-8.1, 5.9 Hz), 1„84 (1H, d, 3 = 5.8 Hz). 3=14.3 Hz). IR (film): 2959, 2857, 1703, 1471, 1391, 1383, 1274, 1215, 1191, 1111, 1103, 1809, 963, 823, 701 cm'1; MS (m / z).: 377 5)., 337 (75), 321 {M'4-57, 8), 319 (10), 309 (10), 293 (6), 259 (12), 231 (20;), 215 (16), 199 (100), 181 (30), 153 (20), 139 (60), 121 (95). (1R,'2S,3-aS,4a'S)-3a-carbemethoxy-2'-tert-butyldiphenylsylliO'X!*1-ethylbbicyclo[3.13Ojhexane [(la10) compound (R=~Eí, P=TSDPS, A=COOCH3)j a) Properties of methyl 1-(1-S,3S,4R,§R)-3-tere-butyldiphenyl-silyloxy-4-ethH-§acetoxykiohexane f(2.1.d) (R = Eí, P=TBDPS, A=COOCHS)] From compound (2*.C) (R=£t:Z=Me, A=COOCHS) we proceed as described for compound (3.4.c). The yield is 92%. ioE 25 : + 7.5 (c=0:.5S, CH 2 Cl); M-NMR (500 MHz, COCh, ppm):. 7.45-7.36 Í10R, m), 4..82 <1H, dl, = 12..2.,. 4.4 Hz). 3.69 (1H, dt, 3=11.5, 4.3 Hz), 3.61 (3H, s), 2.08 (2H„ tt, 3=8.8, 3.9 Hz)., 2.01 (3Η. s), 1.85 <2H, m), 1.60 (3H, m), 1.51 (ΊΗ, m)„ 1.06 (9H. s) 1.02 (3H, t, 3=7.5 Hz); IR (film): 2954, 2848, 1739, 1462, 1428, 1364, 1238, 1194, 1173, 1110, 1034. 986, 812, 740, 702 cm'1. MS (m / z); 482 (M*, 2), 458 (5), 451 (7), 425 (M*-5?),. 391 (1), 365 (8-0), . 351 (25), 305 (15), 273 -(.20),. 241 (100), 213 (38), 199 (92), 153 (58), 135 (75), 107 (SS). > <· fc) 'Methyl-{1 S,3S,4R,5R').-3"tert-butyldiphenylcyclohexyloxy"4-ethyl-5-hydroxycyclohexane keroxylate [(2.2,-d> compound (R=Me, P-TBOPS, A-COOCH3)] Starting from compound A. (2.1.d) (R=Et, P=TBOPS, A=COOCHS) we proceed as described for compound (2..2..c) (R=Me, P=T8OPS, A=COOCH«). The yield is 98%. [AjcT? +28.7 (0=0.19, CH-yCi), 1H-NMR (500 MHz, CDCl?fppm); 7.68 (1QH, m), 3.68 (TH, dt 9=8.2, 4 / 2 Hz), 3.52 (3H, &},. 3.5? (1H, dt, 9=11.1, 4.8 Hz), 2.07 (1H, m), 1.85 (TH, t, 9=4.1 Hz), 1.77 (1H, dt, 9=8.5, 4.0 Hz), 1.71 (1R, ti, 9 = 11.0, 4.ö Hz), 1.64 (2H, t, 9 = 9.0 Hz), 1.59 (1H, overisp), 1.52 (1H, bs), 1.45 (ÍR, m), 1.06 (9H, s), 1.05 (3Η, t, 3=7.5 Hz); IRISH (isim); 3435, 2995, 2856, 1736, 1589, 1460, 1427, 1363, 1271, 1235, 1172, 1111, 1060, 915, 875, 823, 740, 702, 647cfrf'; MS (m / z); 383 (M*-57, 14), 351 (16), 323 (18), 305 (00), 273 (18), 253 (10), 227 (50), 199 (TOO), 183 (70), 153 (80), 107 (OS). c) ^Ethyl~US.,..3-S)4R,5R)-3-tert-bu{yldiphenyl--ylyloxy-4-ethyl-5-toxyloxy-cyclohexanecarboxy!((2,3.0) compound (R = Bt R*TB-DPS, L«0'Tos, A=COOCH3)] Starting from compound (2.2.d) (R=Et, P=TBDPS, A=COOCHS), we proceed as described for compound (2.3.c) (R-Me, P=TBDPS, L-OTos, A=COOOH8). The yield is 82%. Moses; -17.9 (¢=0.59, CH 3 Cl ); 1H-NMR (509 MHz, COCIS{ppm): 7.72-7.30 (T4H, m), 4.28 (1H, dt, 9 = 12.5, 4.5 Hz), 3.59 (3H, s), 3.56 (1H, dt, 3 = 11.4, 4.3 Hz), 2.45 (3H, s), 1 / 96 (1H, ft. 9=8.5, 4.1 Hz), 1.91 (1 H, t, 9=4.2 Hz), 1.84 (TH, dt, 9=8.6, 4.1 Hz), 1.77 (TH, m), 1.73 (TH, m), 1.53 (2H, m), 1.4? (1H, m), 1.02 (SH, s), 0.97 (3H, t, δ=7.5 Hz); IR (film): 2957, 2858, 1738, 1598, 1487, 1462, 1428, 1380, 127 / , 1189, 111 1, 1030,, 853, 886, 822, 741, 704 cm\ MS (ra / z): 35? <Μ*-5?, 45), 353 (100), 293 (2.2). 227 (5), 199 (48), 135 (70). d) (1 R<2S / 3aS,4a:S>-3a»carbemetho.xí-2-tert-fcutif.difen.iisziHtoxM-etii~ bicycle(3,1 .Ojhexane {{La. 10} compound (R=Et, P=TSDPS, A-CO0CHS}] Starting from the compound (2 / 3,d) (R=Et, P=T8DPS, l=ÖToé, A=COOCH3) we proceed as described for the compounds (La.7) (R = Ms, P=T8DPS, A*COOCH8). The yield is 71%. IO 2 S: -3-3.3 (-0=0.27. CHSCI); VH-NMR (500 MHz, CDCk ppm}'. 7.63-7.35 (10H, m)„ 4.18 (1H, t, 9=6.9 Hz), 3.81 (3H, s), 2.26 (1H, m), 2 / 05 (ÍR, m), 1.98 (1H, d, 9 = 14.3 * Hz). 1.92 (W, m), 1.57 H1H. t, 3=4.3 Hz}, 1.4:8 (2H, m), 1.36 (1H, dd, 3=8.7, 3.9 Hz), 1.05 (SH, s}, 0.89 (3H. 3=7.4 Hz); IR (film): 2558, 1723, 1427, 1366, 1298, 1224, 1148, 1111. 1064. 1025, 926, 821, 740, 610, 5Ö7 cm''; MS (m / z): 422 (MO 2), 391 (4), 366 (M+-57, 40), 33'? (8), 287 (12), 269 (10). 22S (8), 199 (85}, 135 (100), 106 (38). 34, .„példa (1S, 2 R, 3 a R, 4a R:}- 3-a - kar bo me t oxi-2 - te re- bu ti ld I te η I lsz 1l1I ο x I-1 - et H bike. P«T8DPS, A=COOCH2)j (a) M eth - (1S, 3 S, 4 R, 5 R) - 3 - m ez í 1 o xi - 4 - eti I - 5 - aceto xii cyclohexáhcarboxHét f(3.4.d) vegyüíet (R=Eí. L=OCH3, Aj= A (2'.c) monotonous-vegyüíel (A.=COOCH3 <R=Et, Z=Me) (0,1 g, 0,41 mmol) és Ef3H (0,30 ml, 2,10 mmol) 5 ml di klór-metánban készült: oldatához MsCí-t (98 μι, 1,23 mmol) csepegtetünk szobahőmérsékleten. A kapott keveréket szobshőmér-sékíeten 10 órán át keverjük, A reakolóelegyet jeges vízre öntjük és eW-acetáttai extraháljuk <3x56 mi). Az egyesített extraktumokat biaCi-oidstiaf mossuk (3x5 ml), ,MgSO4felett szárítjuk és tőményitjük, A kapott maradékot HPLC-médszerrei tisztítjuk elüeasként íz.ooktán / etíl-aoetát 9:10 arányú elegyét alkalmazva. Így kapjuk a (3.4.d) (A=COÖCHj, R=Et, l=ÖMs) fnezííáí-vegyüíeieí (0,11 g, 55 %). IR (film): 2954, 1737, 1641, 1357, 1241, 1175, 952 cm4; H-HMR (560 MHz, COCl3, ppm): 4.87 (1 H, dt 3 = 10.9, 4.2 Hz.},. 4.75 OH, dí, 3=4.5, 10.9 Hz), 3.59 (3H, s), 3.00 (3H,:s), 2.48 (1 H, m>, 2.23 (1H, bs), 2.13 OH, dt, 3=4.2, 11.8 Hz), 2.05 (3H, s), 2.01 (1H, d, 3=8.8 Hz), 1.85 (1H, dt. J = 13.3, 4.5 Hz), 1.83 (1H, m), 1.58 (2H, m), 1.01 <3H, s); :MS (m / z): 322 (M+), SOS, 291, 248, 227, 199, 168. 135, 107, 78, 43 (base key); jaj-o2®: +2.5 (0=1.08, CHCl). b) Meili-O S,3S,4R,SRj-S-mesifoxM-eiliikS-hydroxy.iclkphohexanecarboxyiet [(3.5,6} compound (A=CÖOCH5, R = Et, IL«OMs}j Starting from compound (3.4.d) (R=Et, t=OUs, A=COOCH3) we proceed as described for compound (2.5.3) (R=H, L=ÖTos, A=COOCHs). The yield is 90%. IR (film): 3439, 2957, 1729, 1438, 1351, 1277, 1174, 344, 877, 838, 757, 530 cm'; 'H-NMR (506 MHz., CDCU, ppm): 4.87 (ÍR, t, 3 = 8.1 Hz), 3.91 (1H, t, 3=2.8 Hz), 3.74 (3H. δ), 3.06 (3H, s), 2.63 (ΊΗ, bs, 2, 14 ), OH, 2.14 ). (1X, bs), 2,OO (2X, m), 1.84 (2X, dt, 3=14.3, 4.7 Hz), 1.71 (2X, m). 1.0.3 (3H, t, 3 = 7.4 Hz·: * MS (m / z); 281 (MMh 268, 249, 238, 200, 184, 386, 141, 128, 111 87, 78, 65 (alap-csúcs); [abzs; +51.3 (0=9.61, C-HC'b). c) Me 1i - (1S, 3 S, 4 R, 5 R)3- re and zi 1 -ox I - 4 - and H - S -terc Puííidífenflszíiiíoxieikiobexáncarboxiiáí í(3.5.d) vegyüiet (R=Et, L=OMs. P=T8DPS, A=C0OCH3.)] A (3.5,d) vegulet bői kiindulva (R=Et, L=OMs, A«COOCH3) a (2.8.a) vegymetn-éi (R=H„ L=OTo-s, R=T8DPS, A-=COOCH3) leírtak szerint járunk el. IR (film)· 2SS7, 2857, 1738, 1588, 1462, 1427, 1358, 1276, 1 177, 1111, 1030, 943, 885, 823. 741, 703, 814 cm'l (500 MHz, CDChi ppm); 7.85-7.35 (10H,. re), 4.44 (1H, dt, = 12.2, 4.8 Hz), 3.67 (1H, dl 4 = 11.6, 4.2 Hz), 3.83 (-3H, s), 2.78 (3H, s), 2.09 (1H, dt, 3 = 12.9, 3.3 Hz), 2.06 (1H, re), 2.02 (2H, re), 1.85 (1H, m), 1.79 (1H, db, 3=12.8 Hz),. 1.66, 1H, dt, 3=13.1, 4.0- Hz), 1.49 (1H, re), 1.06- (9H, s), 1.04 (3H, t, 3=7.5 Hz); MS (m / Z>; 451 (M*~57), 401, 365, 351, 305, 277, 231, 199, 187, 135, 107 (skis and snowboards), ; -2.3 (c=0.35, CHCl 3 ). d) (1S,2R,3aR,4aR)-3a-carbomyloxy:-2-tert-butyldpheneHsi1Hox;i-1ethyl-bicyclo(6.1;.OIhe:x-an ((1.111) chemical: et (R=£t, P=TSDPS. A=COOCHS)) Starting from compound (3.5.d) (R=Et, L~OMs, P-TBÖPS, A=COOCH3) we proceed as described for compound (la.7) (R=Me, P=TBDPS, A=COOCH3). The yield is 71-83%. ÍR (film); 2958, 1723, 1427, 1366, 1298, 1224, 1148, 1111, 1004, 102.S, 926, 821, 749, 810, 507 ere'; •H-NMP (500 MHz, CDCíj, ppm); 7,83-7,35 (10H, m), 4,18 (1H, t, = 5,9 Hz), 3,61 (3H. s), 2,25(1 H, re),'2,06(1 H, m), 1,98 (1H, d, 3=14,3 Hz). 1,92 (1H, re), 1,67 (1H, t, 3=4,3 Hz), 1,48 (2H, re),. 1,36 (1Ή, db, = 8,7, 3,9 Hz), 1,05 (9H, s), 0,89 (3-H, J-7,4Hz); MS (re / Z); 422 (M\ 2), 391 (4). 365 (M+-57, 40), 337 (8), 287 (12), 259 .(10):, 225 (8), 199 (65), 135 (100). 105 (38), [ab2S: +28,4 (c = Ö,?5, CHCi3). ne (1R, 2 S, 3 a R, 4 a R) ~3 a - ka rbo m e toxi- 2 - te r e - b-ut ildite n i i s-zi II iοxI-1 - mali l btcíklöfS. 1 .ÖJdexán j(Le,1) vegyület <R=Ms, P-TSÖPS, A=COÖCH3)j a) Methyl-(1 S,3S,4R,5S)-3-tert-butyldiphenylsilyloxy-4-methyl-5-hydroxylcyclohexylcarboxylate (3.2.c) (P=M®, P=78DRS. A=GOOCHS)1 (2.2.e) (R-Me. F=TBDPS, A=CGOCH3) (167 mg, 0.392 rereol), picalic acid (257 reg, 2.092 mmol) and trifemiphosphine (548 mg, To a solution of -33KG~cm of DIAD (diisopropyl azodicarboxylate; 412 μl, 2.092 mmol) in THF was added dropwise over 4 min. The reaction mixture was stirred for 4.5 h and then warmed to room temperature overnight. The mixture was poured onto a mixture of water and ethyl acetate (70 ml). The organic phase was separated, the aqueous layer was extracted with ethyl acetate (3 x 50 ml) and dried over MgSO4. The residue was separated by HPLC (eluent; isooctane / ethyl acetate). 8; 2) k api uka· (4 S, 6 S} -4 - car rb ome tox t -6 -1e rc · bu 11I d í fe η I1 sz 11Η ox 1 l-methylcyclohexene in the form of a colorless oil (142 mg. 88.8%). IR (film): 2853, 2856, 1738, 1428, 1247, 1158, 1111, 1088, 398, 693, 820. 741, 702, 814 cm1: 1H-NMR (500 MHz, CDCIj. ppm): 7.71 <4H, m), 7.43 (2H, m), 7.38 (4H, m), 5.39 (1H, m), 4.25 (1H, bs), 3.80 (3H, s), 2.38 (1H, m), 2.18 (1H, m), 2.13 (1H, m), 2.04 (1H, m), 1.75 (1H, dd, J-22.3, 12.5Hz), 1.66 (3H, bs), 1.05 (8H, s); MS (m / z): 387 (1), 381 (1), 351 (75), 318 (5). 273 (5), 273 (5), 213 (100), 183 (70), 13? (85), 105 (30),. 77 (85); HE*: +81.0 (c~1.91, CHCl 3 ). To a stirred solution of the above cyclohexane compound (110 mg, 0.27 mmol) in 2 ml of distilled water at 0°C was added dropwise a borane-THF complex solution (1.0 M, 325 μΙ, 0.325 mmol, 1.5 equiv.). The resulting solution was stirred at 0°C for 4 h. The THF was removed and ΤΑΌ (triroethylamine-M-oxide, 90 mg, 0.81 mmol) is added. The mixture is heated under reflux for 2 hours. The resulting mixture is cooled to room temperature, extracted with ethyl acetate (4 x 40 ml) and dried over MgSO4. The residue is separated by flash chromatography on silica gel and then purified by BPLC (eluent: cyclohexane / ethyl acetate ~ 9:1). This gives compound (3.2.c) (R = Me,. P = T8DPS, A-COOCHs) as a colorless oil (46 g, 40.5%). IRISH (film, cw'): 3453, 2954, 2858, 1737, 1452, 1428, 1372. 1272, 1195, 1111, 1032, 934, 823, 702; 1H-HMR (500 MHz, CDCl 1 , ppm); 7.68 (4H, m), 7.42 (2H, m), 7.38 (4H, rn), 4.17 (1H, dí, J*10.7. 4„?Hz), 3.88 (1H, bs), 3.82 (3H, sj, 2.81 m), 1.85-1.65 (5H, m), 1.08 <9H.s), 0.98 (3H, d, d-7; 2Hz), αU*S: +39.4 (c«0.8S, CHCIs):. b) Methyl-(1S:3S,4R,5S)-3-tert-butyldifluorosylhexyl-5-methyloxy-4-methylcyclohexanecarboxylate [(3.3.c) compound (R«Me, L=OMs, P-78DPS, A-COOCBs)] Starting from compound (3.2.C) (F«Me, P-TSDPS, A=COOCH3), we proceed as described for compound (3.4.d) (R~Et, LOMs, A^COOCHj). The yield is 84.5%. IR (grass): 2952, 1732, H70:. 1427, 1357, 1275, 1177, 1112, 1029, 929, 904 1H-NMR <500 MHz, COCIs, ppm): 7.65 (4H, t, 3-8.S Hz). 7.40 (8H, m), 4.86 (1 H. bs), 4.06 <1H, m), 3.66 <.3H, s), 2.70 (3H, :$}, 2.58 (1H, m), 2.04 (1.H, bs), 1.98-1.78 (4H, m), 1.06 (9H, s), 1.03 (3H, d, 3-7.2 Hz); (ab25, -30.3 (c«0.52„ CHGIj). c)<lR,2S,3aR.48R)~38-ka:rbometQxi-2-'te'rc> feutiWífenh'SZíh'loxM methiibicyclo[3,t.öjkhexane {(ie,1) compound (R=Me, P=T8DPS. A«COOCH3)j Starting from compound (3.3.e) (R«Me, t«0Ms, P=7BDPS, A=COOCHS) we proceed as described for compound (la.7} (R»Me, P=TBÖPS, A^COÖCHs). The yield is 68.8%. IR (fiira): 2951. 1726, 1428, 1259, 1238, 11 11, 680, 814, 742, 792 cm'1; H-NMR (SOö MHz, C0GI3 ppm); 7.63 (4H, m), 7.45-7.35 (SH, m), 3.84 (1H. m), 3.64 (SH, s), 2.23 (1H, m), 2.02 (1H. m), 1.93 (1Í-L m), I, 60 (1H, ml) 1.17 (1H, ra):, 1.04 (Ί2Η, bs), 0.56 (1H, s)... 3θ....2.£%Α (2 R, 3 a S, 4 a S) - 2 ~ m éti i - 2 - hl d roxi - 3 a - h I droxi ime ti I - b I oik I o [ 3.1.0 jh hex é n [(1 .11} édiyölet (A«CH20H, R-, = Me}j (see 4. reaction) aj (2R,3aS,4aS}-2~hydroxy-3a-((benzoyloxy}raethylj-bicyclo[3.1,Ojhexane {(4.1) or élij To a solution of compound (1.3.5) (R = H. P = TBDPS. A^CHjOH) (4.461 g, 12.15 mmol), DMAP (250 mg, 2.2? mmol) and Et3N (18.5 ml, 121.1 mmol) in dichloromethane (50 ml) at 0*G, benzene chloride was added dropwise. The mixture was stirred at room temperature for 22 hours, then the solution was diluted with 70 ml of dichloromethane. The organic phase was separated, washed with NaCl solutions (3x1 QÖ ml) and dried over MgSO«. The residue was purified by flash chromatography (silica gel eluent; isooctane / ethyl acetate ~ 160:2.5) to give the corresponding benzoate as a colorless oil (5.51 g, 96.5%). To a solution of this benzoate (2.22 g, 4.72 mmol) in THF (40 ml), TBAF (14 ml, 14 mol, 1M solution in THF) was added and the resulting mixture was stirred at room temperature for 14 h. The solvent was evaporated in vacuo. The residue was applied to a short silica gel column (eluent: isooctane / ethyl acetate = 7:3). The crude product was purified by HPLC (eluent; isooctane / ethyl acetate * 7:3) to give (4.1) compound as a colorless oil (1(03g, 94.0%). IR (fiira): 3413.8, 2928.3, 1714.1, 1862.1, 1452.1, 1277.5, 1116.1, 1070.6, 958.3, 808.3, 711.5 cm4; H-HMR (560 MHz. COCi3, ppm): 6.08 (2H. d. 3=7.8Hz), 7.58 (1H, t, 3 = 7.3Hz), 7.45 <1 H. t, 3 = 7.7Hz), 4.48 (1H, m), 4.34 (2H, dd, 3=19.4, II, 5Hz), 2,.23 <2H,. m), 1.94 (1H, 6, 3 = 14.0Hz), 1.78 (1H, d, 3 = 14.2Hz), .* 1.38 (1Η, ddd. 4=8.3', 4.3, 4-.3Ηζ>, 1.30 0Η, bs), 1.06 (1Η, 1, 4-4.4Βζ), 0.75 (1Η, m); MS(m / 2)·: 232 (Μ*. 1), 214 (1), 198 (1), 189(1), 161 (1>, 149 (1), 127 (1), 110 (13), 105 (100), 77 (43), 67 (14); [a) a 2 S: -27.98 (¢=1.47, CHCl 3 ). b) (3aS,.4aS)-3a-[('benzo1foxy>meW3-biCl:ik1o(3..1.0]hexan-2-one ;[(4.2) To a solution of the alcohol compound (4.1) (208 mg, 0.804 mmol) in dichloromethane (30 ml) was added pyridine dichromate (PDC, 1.072 g, 4.07 mmol), and the mixture was stirred at room temperature for 16 hours. The resulting solution was directly purified by flash chromatography (silica gel column, 3x15 cm, eluent: isoctane / ethyl acetate = 9:1 - 8:2), thus obtaining compound (4.2) as a colorless oil (197 mg, 95%). IR (Film)'. 1745.0, 171.5.8, 1451.2, 1355.4, 1272.1, 1155.7, 1111.3, 1069.9, 711.0 cm -7 ; 'H-H'MR (500 MHz. CDCl 3 , ppm): 8.05 (2R, d, 4 = 8.9Hz), 7.58 (1H, t, 4 = 7., 4Hz.). 7.46 (2'H, t, 4=7.SHz), 4.41 (2H, dd, 4=29.-6, 12.7Hz), 2.75 (2H, m)-, 2.41 (1H, d, 4=9-..0Hz), 2.28 (1H, d, 4=9.3Hz), 1.68 (1H, m), 1.10 (1H, t, 4=7.0Hz), -0.37 (1H, t, 4=5.1Hz); small (m / z); 230 (Ml 1), 212 (1), 202 (6,8), 183 (1), 161 (1), 149 (1), 125 (1), 106 (13). 105 (100), 77 (46), 51 (20), {-aJö2S; -36.50 (c=4.07, CHC!3). c) (2R,3aS,4aS)-2-methyl-2-hydroxy-3a-hydroxymethylbicyclo[3.1'.o]hexane (i.1.1) compound (R5sMe, A=CH2O-H) To a solution of the ketene compound (4.2) (120 mg, 0.52 mol) in THF (4 ml) was added dropwise a solution of MeMg in diethyl ether (1.5 ml, 3.0 M) over a period of 5 minutes at -78:1C~oo. The resulting mixture was stirred for 6 hours at this temperature, then warmed to room temperature and left to stand overnight. Saturated aqueous-ice NH4 solution (0.2 ml) was added to quench the reaction. The mixture was passed through a short silica gel column containing MgSO4. The residue was separated by HPLC (eluent; isooctane / ethyl acetate = 5:5) to give the compound (1.1.1) (R.=Me, A=GH2OH) as a white solid (56 mg, 74%). IR (film): 3,288.4, 2831.3, 2858.5, 1459.1, 1370.2, 1280.7, 1183.9, 1135.7, 1111.5, 1084.0, 1016.0, 922.6 cm'; 'H-NMR (500 MHz, CDCIs, ppm); 3.58 (2H, s), 2,OS (1H, d, = 13,7Hz), 2.0-3 (1H, dd., 4=13,8,. 5,0Hz), 1,88 (1H, d, 4 = 1 3.7Hz), 1,76 (1H, d. 4Μ3.8ΚΖ), 1,34 (3H, s), 1,29 <1H, bs). 1.21 (1H, m), 1.14 (1H, t, 4=4.3Hz), 1.11 UH, s), 0.67 (1H, dd. 4=8.4, 4.5Hz): MS (m / z): 124(2), 109 (8), 93 (12), 81 (12), 71 (10), 67 (10), 55 (11), 43 (100); -33.10 (c=lJ7, MeOH), 3 / . (2Ρ,33δ,4^3)-2-^β1ϊΙ~2-θ;0Γθχί-33'-ίθΓ^Η--ΐ)ίοίί«Ιο[3.1 .Ojhexán {(li2) vegyöíet. (R=Me., A=CBÖ)j SO3 / piridíb complex (2,.5 skv., 140 mg) DMSQ CK£C42(500 ul;250 µί) is available today-amjnban (2.5 ekv., 120 ml) is available old (1.1.1) vegyöíet <R<;=Me, A=CH2.OH) (1 ekv., 50 rag, 35 praol) DMSO / CH:2 C. 120 μΙ) used old data After stirring at -15 °C for 1 h at -10 °C to -5 °C, the mixture was poured into a mixture of diethyl ether / NaCl solution. The organic layer was dried (MgSO4). The residue obtained by evaporation of the solvent was purified by chromatography (diethyl ether / isooctane = 1:1 - diethyl ether.isooctane / isooctane / CH2Cl2 = 100:100:1:20) to give (1.1,2) (R3 = Me, A = GHO) as a colorless oil (37 mg, 75%). SR (isim); 3441, 2929., 1094, 1435, 1250, 1105, 1049, 963, 393 cm -1 ; 1H-NMR (500 MHz, CDClj, ppm): 3.81 (1H, s), 2.47 (1H, a, J = 14Hz)., 2.03 (2B, m), 1.91 (1H. t. J=5Hz), 1.8-8 (1H, d, J = 13Hz), 1.31 (UH, d, J = 14Hz), 1.49 (1H, ddt, 3 = 9.5, 1Hz), 1.36 (3B, s); (aj;-,25: -79,.7 (0=1.22, CKCi3). Example 38 (2 R,3aS,4aS)-2-ethyl-2-hydroxy-3a-hydroxymethyl-bicyclo[3.1, O]hexene {(I.1.3) compound (A=CH2OH, R<='Et)j (see 4, reaction scheme) From compound (4.2) we proceed as described for compound (I.I.1) (R3=iMe:, A=CH3OH). The yield is 68.6%-ps. IR (film): 3275.4. 2921.3, 2858.5, 1431.8, 1284.3., 1237.3, 1 122.3, 1058.0, 1027.8, 930.7 cm4, H-HMR (500 MHz, CDCl3. ppm): 3.59 (2H, d, 3 = 5!6Kz), 2.03 (1H, d, 3 = 13.5Hz), 1.89 <1H, dd., 3 = 13.8, 4.9Hz), 1.83 (1H, d, 3 = 13!7Hz), 1.72 (1B, d, 3=1.3,-8Hz), 1.55 (2H, q. 1=6.4Hz), 1.23 (2H, m), 1.15 (ÍR, t, 3=4.2Hz), -1.0-4 (1H, s), 0.92 (3H, t, 7.4H.z), 0.54 (1H, dd, 3=3.4, 4.3Hz); MS (m / z): 133 (2), 123 (4), 109 (12.9), 97 (2), 91 (6), 79 (20), 7.2 (6), 57 (12.6), 57 (100), 43 (8); [α]ds: -34.90 (0=0.828, MeOH). Example 38: ^R-SaS-AaSl^-ethyl-2-hydroxy-3-a-formyl-bicyclo 1 .Gjhexar [(1.1.4) compound (A=CHO, R5=Et)l Starting from the compound (1.1.3) (Ri=Et, A=OHaOH) we proceed as described for the compound (:.:.2) (R,=Me. A=CHO). The yield is 50%. IR (film): 3418, 2966, 1889, 1114, 1057, 982, 632 cm'';. 4δ' H-NMR (SÜO MHz, CDCis, ppm): 8.80 (1H, -s), 2.OS (2H, m), 1.92 (1H, i. 3=5.ÖHz), 1.83 (1H, d, 4-13.3Hz), 1.69 (1H, d, 3 = 10.öHz), 1.57 (2H, m), 1.49 (ÍH, m), 1.15 (1H, S), 0.93 (3H, t, 3 = 7.4Hz); (ajc25: -68.1 (c=ö.30, CHCIS). 10,..SáJda (2 R, 3 a S, 4 a S) - 2 - i (t - but ii. d I fen fi s íl iioxt) - ms 1i lj»3 a ·· h í drcx 1 met H bi-cik.ío(3.1.0jh©xane |(lj.l) compound (A=CH;OH, P=TBDPS)j (see 4, reaction scheme) a) {3aS,4.aS)-2-methylene-3a«{(benzoyloxy)-methyl-bicyclo[3.1.6]hexane ((4.3) compound] Zinc powder (5.75 g) in dibromo-mephane (2.02 ml) and THF (40 ml) was mixed at -78 °C and TiCl 3 was added dropwise over a period of 10 minutes. The mixture was allowed to warm to 8 °C; then stirred at this temperature for 72 hours. A thick gray soot-like material was thus obtained, which contained the active substance (Lombard reagent). To a solution of the ketone compound (4.2) (98 mg, 0.428 mol) in dichloromethane (8 ml) was added Lombardo's reagent portionwise at room temperature until the ketone disappeared (TBC). The reaction mixture was diluted with diethyl ether (40 ml) and saturated NaHCO3 solution was added, followed by stirring for 30 min; two clear phases were obtained. The aqueous phase was extracted with diethyl ether (3x25 ml) and dichloromethane (2x25 ml). The combined organic phases were dried over MgSO4. The residue was flash chromatographed (silica gel, eluent: pentane / ether ~ 100:1) to give compound (4.3) as a colorless oil (65 mg, 57.9%). Irish (film): 2925.8, 1715.8, 1451.5, 1269.7, 1111.0, 1069.0, 1028.1, 741.9, 710.7 cmx: M-NMR (SÖÖ MHz. COCÍ3, ppm): 8.07 (2H, d, 3 = 7.3 Hz), 7.56 (1H, t, 3 = 7.4 Hz), 7.45 (2H, t, 3 = 7.7 Hz), 4.81 (2H, d, 3 = 12.4 Hz), 4.38 (2H, s), 2.68 (2H, ro), 2.43 (ÍH. d, 3=1 5.4 Hz), 2.28 (1H, d(. 3 = 15.6 Hz), 1.36 (1H, m), 6.68 (1H, t, 3 = 6.5 Hz), 0.39 (1H, t, 3 = 4.6 Hz); MS (m / z): 228 (M*, 1), 213 (1), 199 (1), 181 (2), 169 (1), 141 (1), 123 (5), 105 (100), 91 (88), 77 (57), 65 (7), 51 (20), («jó28: -51.90 fc~ 1,.73,.CHC13). b) ( 2 R, 3 s S, 4 a S} -2 -{(t - b utl I. d I fen i sz III í ox í) - me ti i ] - 3 a - bid ro (2S, 3aS, 4aS)-2-((t~bu ti idifecilszililoxi)-roef 11 j-3a-hídroximet.íibiciklo(3.1.0jhexán |(l..k. 1) vegyület (A=CHSOH. P=TBDPS)j To a solution of the alkene compound (4,3) (45 mg, 0.21 mmol) in THF (6 ml) at -5 °C was added SHs.TP-ef and the reaction mixture was stirred at this temperature for 3.45 h. The reaction was quenched by the addition of saturated aqueous NaHCÖaν* (3.9 ml) and HjOj (30 %, 3.9 ml). The reaction mixture was allowed to warm to room temperature and stirring was continued for 7.5 h. The solution was extracted with diethyl ether (2x20 ml) and ethyl acetate (2x20 ml). The combined organic phases were dried over MgSO4 and concentrated. The residue was applied to a short silica gel column and the resulting crude product was purified by HPLC (eluent: isooctane / ethyl acetate = 7:3) to give a mixture of epimeric hydroxylated products as a colorless oil (2R:2S ratio = 75:25, 39 mg, 73.7%). To a solution of the above mixture (35 mg, 0.142 mmol, imidazole (49 mg, 0.720 mmol, eq.) and DMAP (2.5 mg, 0.064 mmol, 0.45 eq.) in DMF (3 ml) was added TBDPSC1 at 0 °C and the resulting mixture was stirred at room temperature for 19 h. The reaction mixture was poured into diethyl ether / water (50 ml / 40 ml) and the aqueous phase was extracted with diethyl ether (3 x 20 ml) and ethyl acetate (2 x 20 ml). The combined organic layers were dried over MgSO4 and concentrated. The residue was purified by flash chromatography (silica gel, eluent: isocyanate / ethyl acetate ~ 100:2) gave the corresponding diethyl ethers as a colorless oil (56 mg, 81.3%). To a stirred solution of this mixture (50 mg, 0.106 mmol) in MeOH (6 mL containing 0.2 mL of H2O) at room temperature was added K2CO3 (50 mg, 0.505 mmol). The mixture was stirred at room temperature for 20 h, the solid was filtered off, the filtrate was diluted with diethyl ether (50 mL), washed with RaCl solution (2 x 20 mL), dried over MgSO4, and the solvent was evaporated. The residue was passed through a short silica gel column and then separated by HPLC (eluent: isopropanol·acetate = 75:25) to give compound (1.j.7) (A-CH2OH, P=TBDPS) (24 mg, 61.8%) and compound (1.j.1) (A=CH2OH, P=TSDPS) as colorless oils (8 mg, 20.4%). MS (m / z): 379 1., SOS (1), 275 (2), 229 (2), 109 (47), ISI (7), 107 (100), 79 (53). The compound (í.ji) is ÍA=CH2OK, P=TBDPS): IR (film): 3342.5) 2930.3, 2655.0, 1471.8, 142.7.7, 1389.8, 1117.9, 1008.2, 823.7, 733.7, 701.8 cm!; 'R-RMR (500 MHz., CDCIS, ppm): 7.84 (4H, d, <j=?,SHzj, 7,43-7,35 (6H, m), 3,.54 (2R„ dd, 3=14,.4, 11,2Hz), 3,41 (2R, d. J = 7,4Hz), 2,61 (1H, m), 2,1 9-2,03 (2H, m), 1,64 (ÍR, dd, 3=13,5, 4,8Hz). 1,47 (1H, dd, 3=73,8. 4,6Hz), 1,26 (1H,. bs), 1,18 (1H, dt, 3=8,6, 4,3, 4,3Rz), 1,02 (9H, s), 0,82 (1H, dd, 1=8,4, 4,7Hz), 0,35 (ÍR, t, 3=4,4Rz): (ab25) -7 3.05 (C=1.40. CHCÍ7. Az (ik 1) vegyüiet (A=CH2OH, P=TBDPS): IR (film): 3342.5, 2229.9,. 2.856..7, 1477.8, 1427.7 7086.1, 1031.5, 1008.5, 823.7, 739.3, 701.5 cm'5, 1388.8. 1717.9. !H~RME (500 MHz, COCI3, ppm); 7.64 (4R, d, =5.7Rz), 7.39 (<6H, te), 3.64 (7H, d1 = 11.2Hz), 3.57 (3H, d1 = 7SHz), 1.971,87 (2R, te). 1.8Q (1H, dö, 1 = 12.3, 7.0Hz), 1.56 (<2H). te), 7.22 <1H, te), 1.16 (7H, dd, 1=5.3, 4.1, 4.1 Hz), 1.02 (9H, s), 0.52' (1 H, t, 1=4.3Hz), 0.41 (1H, dd, = 8.0, 5.0Hz). (ajö2í; -5,15 (0=1,66, CKCi3). 41. Target (2R,3sS.4a5)2-1(f"biRidiphenyl4silyloxy)-teethyl-3a-forteubic1e[3.1.Ojhexane ((1.).2)-compound (A=CHO, P=TSDPS)j (see reaction scheme 4) (CO-Cl)2 (3-0 µl, 0.344 µl) in dichloromethane (1 ml) was added dropwise at -78 *C to a solution of DMSO (36.6 µl, 0.515 mmol) in dichloromethane (100 µl). The mixture was stirred at 100 °C for 1 h. The mixture was stirred at -76 °C for 20 min, then a solution of compound (lj7) (A=CH2OH, P=TEDPS)(14 mg, 0.37 mmol) in dichloromethane (0.5 ml) was added. The resulting white suspension was stirred at -78 °C for 20 min, triethanolamine (0.2 ml, 7.435 mmol) was added dropwise, then stirring was continued for 20 min. After this, the mixture was allowed to warm to room temperature and stand for 1 h. The reaction was quenched by addition of cold water and the organic phase was separated, the aqueous layer was extracted with diethyl ether (3x5-0 ml) and dried over MgSO4. The residue was separated by HPLC (eluent: hexane / ethyl acetate = 95:5) to give compound (112) (A=CBO; P=78DPS) as a colorless oil (4 mg, 28.7%). IR (philte): 2031, 2858, 1609, 1425, 1112, 524, 740, 613 cm'1; 1H-NMR (550 MHZ, CDCb, ppm); 8.83 (7H, s). 7.63 <4H, d, 2?.4Hz), 7.68-7.35 (6H, te), 3.43 (2H, d, 2=5.5Hz), 2.68 (2H, m), 2.18 (7H, te), 2.02 (1H, te), 1.59(1H, te), 1.51 (1H, d, J=S,0Hz). 1.25 (ÍH, fos), 1.02 (OH, $), 0.90 (1H, te); MS (m / z): 337 (4), 307 (2), 293 (4), 259 (2), 217 (9). 199 (54), 183 (20), 135 (24), 705 (30), 23 (109); {α) / s: -52.6 (c=0.27, CRC13). (gS.'SaS.^aS'j-^-Kt-butyldiphenylo-X-methyl-S-formyl-2-ylhexyl (sl.k.2) -compound (A=CHÖ, P=OT8DRS)j (see tube frame wall) Starting from compound (ik7) (A=CH2QH, P=T8DPS), the procedure is as described for compound (ij2) (A=CKO, P=T3DPS). The yield is 92.8%. IRISH (flite): 2932, 2868, 1703, 1471, 1427, 1112, 624, 741, 702 dte'1; ·* φ< 1H-NMR (500 MHz, CDCb.ppm): 8.98 (1H, s), 7.63 (4H, m), 7.487.35 1H, m), 3.58 (2H, m). 2.05-1.88 (SH, m), 1.62 (1H, m), 1.34 (1H, dd, 3-8.5, 5.5Hz), 1.20 (1H, t, 3 = 6.4Hz), 1.02 (9H, s); MS (m / z): 337 (15), 259 (14), 231 (30), 159 (100), 137 (20), 83 (60), 77 (70). Example 3 (2S,3aS,4aS)-2-methyl-2-hydroxyl-3a-hydroxysmethyl-bcyclo[3.1.O]hexane [(IJ.1) compound (A=CH2OH, R=CHa)] (see Scheme 4) To a solution of Hg(OAc)j (350 mg, 1.10 mmol) in water (1.5 ml) was added dropwise a solution of compound (4.3) (164 mg, 0.719 mmol) in THF (1.6 ml). After stirring at room temperature for 30 min, aqueous HaOR solution (1.5 ml, 3N) and then 0.5M NaBH43N in NaOH (1.5 ml) were added. The resulting mixture was stirred at room temperature for 2 h until most of the mercury coagulated. The solid was filtered off and the extract was extracted with diethyl ether (2x30 ml) and ethyl acetate (2x30 ml). To the residue were added KaCO3 (500 mg, 5.05 mmol) and M-eöH (2 ml). The mixture was stirred for 20 h at room temperature. The reaction mixture was passed through a short silica gel column. The crude product was purified by HPLC (eluent: cyclohexene / ethyl acetate = 62:45) to give compound (1.1.1) (A=CH?OH, R<=Me) and compound (1.1.1) (A=CH2OH, Rt-Me) as a colorless oil (ratio; 3-:1, 68 mg, 66.614)· IR (film): 3288.4, 2931.3, 2858.5, 1459.1, 1370.2, 1260.7, 1163.9, 1136.7, 1111.5, 1064.0, 1018.0, 922.8 cm -1 ; 1H-NMR (500-MHz, CDCis, ppm): 4.02 (1H, d, 3=10.7Hz), 3.0? (1 H, d. 3 = 10.7Hz), 2.05 (2H, m), 1.65 (ÍR, bs), 1.52 (1H, d, 3=12.8 Hz), 1.37 (-3H, m), 1.25 (3H, s), 1.66 (1B, dd, 3 = 8.0, 4.8Hz), 0.49 (1H, t, 3=4.3Hz). (2S,3aS,4a8}-2-methyl-2-hydroxy-3a-formyl-bi 1 chloro[3.1.0]hexane [(1.1:.2) compound) (A=CHO, R-'Mejj (see reaction scheme 4) Starting from compound (1,).1) (A=CH2OH, R4=Mie) we proceed as described for the radicals of (1,).2) (A=GHÖ, P=7BDPS). The yield is 4 8.2%. IR (film): 3429, 2987, 2923, 1691, 1377, 1249, 1102, 1038, 668 cm? 'H-NMR (500 MHz, GDGIa> ppm): 8.90 (1H, s), 2.68 (ÍR, dd, 3 = 14.3 2.4Hz), 1.96 (2H, m), 1.68 (1H, dd, 3 = 8.5. 5.2Hz), 1.65 (1H, bs), 1.51 (2H, f, 3=14.2Hz), 1.31(3H, s), 1.14, (1H, t, 3=5.2Hz); MS (m / z): 140 (M\2), 123 (10), 11 1 (10), 97 (15), 85 (25), 71 (25). 67 (30), 46 (100): β2δ: 39.3 (e=1.06, CHCl5). * •X (2S.3aS,4sS)-2-hydroxy-2-hydroxymethyl-3s-((benzoyloxy)methyl)bicyclo[1] compound (A=CH3OCOPh}] {see reaction 4; To a mixture of compound (4.3) (55 mg, 0.285 mmol) and NMO (43 mg, 0.344 mmol, 1.21 eq.) in acetone / water (5 ml:2.5 ml) was added an aqueous solution of OsO4 (121 µl, 0.02 mmol, 4 wt%, 0.07 eq.) at 0°C. The resulting solution was stirred for 39 h at room temperature, then sodium dichloroethane (70 mg) and Fluorosil (100 mg) were added. The black precipitate was removed by filtration and washed with diethyl ether (200 ml). The solvent was evaporated under vacuum. The residue was dissolved in diethyl ether containing a small amount of acetone (100:5) and the material was filtered through a Flurosil pad. The crude product was separated by HPLC (eluent: cyclohexane / ethyl acetate = 7:3) to give (im) or (ii) along with a small amount of the C-2 epimer (ratio = 85:15) as a colorless oil (54% overall yield). IR (film): 3:385,5. 2927,8, 1713,7, 1451,6, 1315,2, 1274,8, 1114,7, 1G7Ö.3, 1026,2, 934,8, 711,5 om'l1H-.NMR (500 MHz, CDCIS, ppm): 8,06 (2H, d, 4 = 7,3Hz), 7.57 (1 H, t, 4=7,4Hz), 7,46 (2H, t, J = 7,8Hz), 4.48 (1H, d, J=í1,5Hz), .4,21 (1H, d, 4=11,5Hz), 3,48 <2H, m), 2,58 (1H. s), 2.35 (1 H, s), 2,18 (1H, d, 4=14,6 Hz), 2,12 (1Ή, dd, 4=14,2, 6,3Hz), 1,94 (1 H, t, 3=14,1Hz), 1 „89 (1H. í, J = 14,1Hz). 1,85 (1H, d, 4=14,2Hz), 1,07 (1H, dd, 4=8.,4, 5,3Hz), 0,47 (1H, t, 4=4v6Hz); MS (m. / z):: 262 (M\ 1), 244 (1), 232 (3), 213 (4), 203 (31, 178 (1), 183 (4). 145 (4),, 123 (15), 108 (100), 77 (52), 67 (13); í«lo£S: -11,86 (c=1,S3„ CHC)3j.< / etoh> < / kbr>

Claims

1. Process for the preparation of compounds of general formula (I) - where in the formula - A is -CH2GH, -CH2-G€OR', -CGR', -C-SR” or ethyl group; - R is a hydrogen atom or a Ο-,-Cg alkyl group; - Ri is a hydrogen atom, a Ci-Cs alkyl group or a -(CH3b-OR group; - Rs is a hydrogen atom or -OP; - R' is a C<-Cs alkyl group or a phenyl group; - R is a hydrogen atom, a hydroxyl group, a Cα-Cs alkyl·, a Ci-Ces alkoxy-., a Ci-Ces alkylthio- or di (0-..-0¾ alkylamino-group; - P is a hydrogen atom;; a C~C« alkanol group; a benzoh-group, in which the phenyl group is optionally substituted by a CsC^ alkyl group, a halogeno-aromatic group or a nitro-group; (C,-Cs alkoxides.arbonyl group; -Si(R3)3~ group, where the Rs groups independently represent C1-C5 alkyl or phenyl groups; mono- or di(C <vCg alkoxi}(C;-C5 alki Ij-csoport; fetrahidrofursnll-csoport vagy t-etrahidropiranii-c-soport;' - n jelentése 0, 1, 2,-3 vagy 4; azzal jellemezve, hogy i) egy O) általános képletű vegyületet - a képletben A jelentése (CrC« alkox5)karbo-nil-cso-port vagy diíC.-Cj alkiijarninokarbo-níi-csoport és R jelentése a fentiekben megadott - egy lipázzai reagáltatunk vmilatkanoáíban vagy savsnhldridben, és íl) a kapott (2) vagy (2'j általános képietü vegyületet - s képletben Z jelentése alkilcsoport, előnyösen C-i-Cs áikilcseport - a megfelelő (I) általános képletű vegyüi-etté alakítjuk.

2. The process according to claim 1, characterized in that a compound of general formula (1) is prepared, wherein A is methoxycarbonyl.

3. The process according to claim 1 or 2, characterized in that the vinyl acetate is selected from the group consisting of vinyl acetate, vinyl propionate and vinyl butyrate.

4. The process according to any one of claims 1 to 3, characterized in that the acid anhydride is selected from the following group: acetic anhydride, propionic acid anhydride and butyric acid anhydride.

5. The method according to any one of claims 1-4, characterized in that the ilpase is selected from the group consisting of SAM II, PPL, CCL, PSL and GCL.

6. The process according to any one of claims 1-5, characterized in that step (i) is carried out at 10-40°C.

7. The method according to any one of claims 1-5, characterized in that step (B) is performed at a rate of e-7'2'.

8. The process according to any one of claims 1-7, characterized in that during step (iii) one or more steps are carried out selected from the following: - protection of hydroxyl groups, - ester saponification, - inversion of the 3- or 5-hydroxyl group, - formation of a leaving group. - ring closure with a base to produce the desired bicyclo[3.1.0} hexane, - conversion of the carboalkoxy or carbamoyl functional group to the desired A substituent.

9. Compounds of general formula (2) or (3) * where in the formula - A. represents a (C,-C5 alkoxycarbonyl group or a (C1-C3 alkylaminocarbonyl group; - R represents a hydrogen atom or a C1-C6 alkyl group - 2 represents an alkyl group, 10. Compounds of general formula (1), wherein in the formula: A is as defined in claim 5 and R is a C1-C8 alkyl group.