FI92843C - New method for preparing optically active glycerol derivatives - Google Patents

Description

92843

NEW METHOD FOR THE PREPARATION OF OPTICALLY ACTIVE GLYCEROL DERIVATIVES - NY METOD FÖR FRAMSTÄLLNING AV OPTISKT ACTIVE GLYCEROLDERIVAT

The invention relates to a new process for the preparation of optically active 1-monoacylglycerol or 1,2-diacylglycerol derivatives.

The optically active glycerol derivatives prepared by the process of the invention are useful as starting materials for the preparation of important optically active glycerophospholipids. These optically active glycerol derivatives are still useful as starting materials for the preparation of therapeutically valuable PAF factors as well as β-blockers.

Phospholipids comprise a wide group of compounds, the most important of which are derivatives of L-phosphatidic acid, which are phosphoglycerides and are also called glycerophospholipids. The formula for L-phosphatidic acid is

15 H2COOCR

R'COO ^ H ^ (A) n21-o-I> -OH 0 '

Phosphate esters of L-phosphatidic acid of general formula 20 HO

/ \ J / \ I <B> RO ^ \ | / N0P0R "1 0 'R'0 25 wherein R and R' are acyl groups and R '' is an amino-substituted alkyl group, are important phospholipids.

Glycerophospholipids occur in nature and are important components in the 2,92843 membranes of cells in living organisms. Glycerophospholipid molecules are amphipathic, i.e., have a lipophilic moiety formed by long hydrocarbon chains and a hydrophilic moiety formed by a dipolar phosphate group.

Glycerophospholipids form vesicles in certain solutions, the wall of which consists of a bilayer of glycerophospholipids such that the lipophilic hydrocarbon chains of both molecular layers extend into the wall, while the hydrophilic groups of the molecules extend to both surfaces of the wall. Such a double layer is able to selectively control the passage of different types of substances from the wall. The liposomes used, for example, to release different types of drugs consist of one or more bilayers of glycerophospholipids.

In order for a glycerophospholipid to be able to form the desired bilayers, it is important that the molecule be a suitable stereoisomer. Naturally occurring glycerophospholipids are just pure stereoisomers, not racemates.

An important glycerophospholipid found naturally in human basophils is platelet-activating factor (PAF). The formula of this compound (1-10-alkyl-2 (R) -acetyl-sn-glycero-3-25 phosphocholine) is

H O

Rcr \> - p-o-ch2ch2n + (Ch3) 3

CH 3 COO

30 wherein R is a straight alkyl chain containing 16 or 18 carbon atoms.

The main naturally occurring phospholipids of the glycerophospholipid type 3 92843 are lecithins and their main sources are egg yolk, bovine brain, red blood cells and soybeans. Lecithins are used for many different purposes, mainly as food emulsifiers. Natural lecithins are mixtures of different glycerophospholipids in which in the compound of formula (B) R is typically saturated C16 to C18 acyl, R 'is typically unsaturated C16 to C20-ayl and R' 'is the choline group CH2CH2N + (CH3) 3.

10 However, glycerophospholipids for drug delivery must be both chemically and optically pure compounds, not mixtures. Only synthetically prepared glycerophospholipids are suitable for these purposes.

Synthetically prepared, pure optically active stereoisomers of glycerophospholipids are usually the result of multi-step and complex processes. In the syntheses it is necessary to use e.g. many different protecting groups to selectively prepare the desired derivatives and to prevent isomerization of the intermediate acylglycerol. The difficulty with glycerol phospholipid syntheses is precisely the preparation of a pure optically active glycerol derivative and the maintenance of the optical activity of the glycerol derivative during the multi-step synthesis. Total 6- to 14-step syntheses of glycerophospholipids using D-mannitol (1), L-serine (2), or allyl alcohols using Sharples asymmetric ·· epoxidation (3) have been published. As an alternative to the above methods, enzymatic stereoselective acylation of prochiral glycerol derivatives using acyl donors has also been reported in the literature, but the purity percentages of optically active stereoisomers, depending on the enzyme used and solvent conditions, have been at most 96% (4%).

4,92843

According to recent publications, the number of reaction steps has been reduced to five, but these syntheses have either used an expensive, pure optically active starting material (5), or the starting material has been synthesized in 5 multi-step reactions (6).

(9), (16) and (23) to (26) describe the enzymatic acylation of 2-O-benzyl-1,3-propanediol. The course of the stereospecific acylation reaction catalyzed by the enzyme is influenced by many factors such as the enzyme strain, the substrate molecule, the acyl donor, the solvent, the temperature, the amount of water in the reaction, and the stirring rate. It can be seen from the literature that in each article describing the stereospecific reaction catalyzed by the enzyme, a considerable number of experiments have had to be performed before the optimal conditions have been found. Therefore, the acylation conditions of 2-O-benzyl-1,3-propanediol cannot be directly adopted? the enantioselectivity of the reaction may be, for example, just the opposite. The use of racemic 3-O-benzyl-1,2-propanediol in phospholipid synthesis compared to prochiral 2-O-benzyl-1,3-propanediol is in many ways a better alternative because 1) fewer steps are obtained in the synthesis of phospholipids, 2) both stereoisomers of phospholipids can be prepared , with both a symmetrical and asymmetric fatty acid composition, and 3) 3-O-25 benzyl-1,2-propanediol is a much more readily available and significantly cheaper reagent than the corresponding 2-O-benzyl-1,2-propanediol.

The object of the present invention is to eliminate the above-mentioned problem and to provide a new process for the synthesis of optically active glycerol phospholipids which does not have the above-mentioned drawbacks.

The invention relates to a process for the preparation of optically active 1-monoacylglycerol or 1,2-diacylglycerol derivatives * · k 11 5 92843 / having the general formula

R1 - <? - cr X \} - X (I) HCl ^

5 S / \ / \ · / \ A

R 1 -CO 2 X, O-X or R 1 -CO 2 Λ, Ό-Χ a ^ -c-r 2 R 2 - | -O 2 (Ha) (Hb) 10 wherein X is an easily removable protecting group Y or hydrogen, wherein the protecting group Y may be unsubstituted or substituted benzyl or trityl or a silyl group Si (R) 3, wherein the R substituents may be the same or different and are alkyl or aryl groups; R 1 and R 2, which may · .; 15 may be the same or different, are a C 1 -C 28 alkyl, a C 2 -C 28 alkenyl or alkynyl group or at the same time both an alkenyl and an alkynyl group, in which the number of double or triple bonds may be one or more. According to the invention, a racemic compound of formula (V) is obtained.

OH

in the presence of a lipase enzyme acting as a catalyst to react with the anhydride RjCOOOCRj or a compound of formula (III) of formula R1COOR3 (III), wherein Rj is the same as before and R3 is a vinyl, trifluoroethyl or isopropenyl group, either a) to a compound of formula (I), wherein X is a protecting group Y and which compound is isolated from the reaction mixture and optionally i) optionally hydrogenated to remove the protecting group Y, or ii) esterified with an acid R 2 C 10 H wherein R 2 is the same as before and may be the same as or different from R 1 to give the formula A compound of formula (IIa) or (IIb) wherein X is a protecting group Y, which is optionally deprotected by hydrogenation, or b) a compound of formula (IIa) wherein X is a protecting group Y and R 2 = R 2, followed by optionally catalytically hydrogenated to remove the protecting group Y 10.

Suitable substituents on benzyl or trityl protecting groups include, for example, lower alkyl, lower alkoxy or nitro.

The protecting group is preferably benzyl and the lipase enzyme lipase PS or lipase AK.

In the above formulas (I) and (II), X is preferably · benzyl and Rx and R2 are similar groups.

Within the scope of the above formula (I) is a previously known compound in which R 1 is a C 15 H 31 alkyl or C 17 alkenyl group.

The literature (16) mentions optically active 1-stearoyl-3-benzyloxy-2-propanol, but its stereochemistry is not specified. Compounds of formula (II) are known in which R 1 or R 2 is direct C 15 H 31 alkyl or direct C 17 H 35 alkyl.

The compounds of formulas (I) and (II) are useful starting materials for the preparation of valuable glycerophospholipid compounds of formula (IV) *.

II

7 92843

H O

η, χ / λΨ ^ ν> -1-ο- «, lIV) 5 O-C-R; o wherein R 1 and R 2, which may be the same or different, are preferably a C 14 to C 25 alkyl, C 14 to C 25 alkenyl or alkynyl group, or both an alkenyl and an alkynyl group, wherein the number of double or triple bonds may be one or several, and R 4 is -CH 2 CH 2 N + (CH 3) 3, -CH 2 CH 2 N + H 3, or -CH 2 -CH (OH) -CH 2 (OH). A compound of formula (IIa) or (Hb)

15 ^ 0-X or Rx-C-o 't> -X

ii--C-R2 R2-j? -cr

O O

(Ha) (Hb) wherein R 1 and R 2 are as above reacted with a phosphorus reagent such as phosphorus oxychloride or 2-chloro-2-oxy-1,3,2-dioxaphospholane to give a compound of formula (IV).

Glycerophospholipids in which R3 and R2 are similar and contain 14 to 25 carbon atoms are best suited for liposome preparation.

The starting material used in the process of the invention for the preparation of the glycerol derivative of the formulas (I) or (II), the racemic compound of the formula (V) 8 92843

/ \ A

OH T OY (V)

OH

can be prepared by a one-step method described in the literature (7). The yield is about 80%.

As acyl donors, vinyl, trifluoroethyl or isopropenyl derivatives of a suitable carboxylic acid can be used. The preparation of vinyl and trifluoroethyl stearates is described in references (8) and (9), respectively, and the yields are 60% and 83%, respectively. The acid anhydride is also a suitable acyl donor (20). In lipipase-catalyzed esterification, only vinyl and trifluoroethyl stearate have been tested as acyl donors, and of these, the vinyl derivative gave more reproducible results. Reaction times and the amount of enzyme used depend on the nature of the acyl donor and must be optimized on a case-by-case basis.

J The racemic diol is subjected to lipase enzyme-catalyzed enantioselective acylation by so-called by the principle of 20 successive resolutions (10) to give either optically pure 1-acylated 3-benzyloxy-2-propanol or 1,2-diacetylated 3-benzyloxypropane depending on the reaction time.

The idea of a synergy of enantio-25 selective reaction and kinetic resolution is implemented in sequential resolution. The method is based on the premise that the reactions performed are irreversible and no inhibition of the final product occurs. For each an kinetic overview of the enzymatic transformation should be obtained first in order to optimize the chemical yield and optical purity of the desired chiral final product. The kinetics of biocatalytic acylation are affected by e.g. batch activity and amount of enzyme used.

A lipase-catalyzed racemic reaction of formula (V)

II

Reaction of 9,92843 with the aforementioned reagents R 10 OOR 3 or R 10 CO 3 yields an optically pure 1,2-diacylated derivative of formula (IIa) or an optically pure 1-monoacylated derivative of formula (I) depending on the reaction time. The monostearylated product is formed rather non-selectively in the first stage. The actual resolution takes place in the second acylation step, in which the (S) -monostearylated enantiomer reacts to the distearylated product considerably faster than the 10 (R) form.

The phospholipids having a symmetrical fatty acid composition can be easily prepared with the intermediate (IIa) synthesized according to the present invention. (R) - or (S) -phospholipids having an asymmetric fatty acid composition can be synthesized starting from compound (I). By acylation of the 2-position of intermediate (I) directly with the desired fatty acid by a method known per se (13), (S) -phospholipids are obtained after known steps (14), (15). By performing Mitsunobu-type inversion acylation (17) on intermediate 20 (I) using the desired fatty acid and supplementing the synthesis by known methods (14), (15), (R) -phospholipids having thus an asymmetric fatty acid composition can be prepared.

The invention is concretely described below by way of examples, but is not limited thereto.

Example 1

Optically active (R) -1-stearoyl-3-benzyloxy-2-propanol and optically active (S) -1,2-distearoyl-3-30 benzyloxypropane These compounds were prepared by enzymatically catalyzed site and stereoselective acylation. Two reactions were initiated, one of which was stopped when conditions were optimal for 10,92843 enantiomerically pure monostearylated glycerol iodine. The second reaction was stopped when the conditions were optimal for the enantiomerically pure distearylated glycerol derivative.

The analysis used was based on the detection of optically active isomers of monostearylated benzylglycerol using chiral HPLC (Chiralcel OD, hexane / 2-propanol = 95/5, 0.9 ml / min, 254 nm).

The reaction vessel was flame dried under argon.

50 mg (0.275 mmol) of (±) -3-benzyloxy-1,2-propanediol were dissolved in dry diisopropyl ether (2.5 ml, solvent dried by molecular sieve). 196 mg (0.632 mmol) of vinyl stearate were added. The reaction was started by adding 50 mg of lipase (Lipase 15 Amano PS, Pseudomonas cepatia) to the clear solution. The suspension was shaken at room temperature (22 ° C) and 400 rpm for several hours, and the progress of the reaction was monitored by chiral HPLC. Isolation of enantiomerically pure monostearylated benzylglycerol was performed after a reaction time of 505 minutes and isolation of enantiomerically pure distearylated benzylglycerol was performed from a second reaction vessel after a reaction time of 385 minutes.

After the reaction was sufficiently advanced, the enzyme was removed by filtration and the solvent was evaporated on a rotary evaporator. Excess vinyl stearate was separated from mono- and distearylated benzylglycerols, respectively, by flash chromatography (19) on a silica gel column (25 g of silica gel). From the reaction mixture from which it was desired to isolate optically pure (S) -1,2-distearoyl-3,3-benzyloxypropane, the product was eluted with 5% ethyl acetate / hexane to give a yield of distearylated product of 81.9 mg (42%). The results of 1 H NMR and GC-MS analyzes corresponded to those reported in the literature (3), (16). The optical purity of the compound was determined after 1 H NMR and 35 polarometric results. For NMR analysis, the compound was deprotected as tl 11,92843 in Example 3, followed by formation of a Mosher ester derivative as described in literature (3). 1 H NMR (400 MHz, CHCl 3): ε> 95%, · [α] D + 4.61 ° ± 0.05 (CHCl 3).

From the reaction mixture from which it was desired to isolate optically pure (R) -1-stearoyl-3-benzyloxy-2-propanol, the product was eluted with 20% ethyl acetate / hexane to give a monostearylated product yield of 50.8 mg (41%). The structure of the compound was determined by 1 H NMR and GC-MS analyzes.

10 H NMR (400 MHz, CHCl 3): δ (m, 5 H, C 6 H 5) δ 4.56 (s, 2 H, O-CH 2 -Ph), 4.17 (m, 2 H, CH 2 -OCO), 4.04 (m , 1H, CH (OH)), 3.53 (m, 2 H, CH 2 -O-CH 2 Ph), 2.48 (s, 1H, OH), 2.32 (t, 2 H, CH 2 CO), 1.60 (m, 2 H , CH 2 (CH 2) 14), 1.25 (m, 14 H, CH 2), 0.88 (t, 3 H, CH 3).

MS (EI +): m / z 520 (M +), 505 (M - CH 3 - Ph), 429 (M - CH 2 -Ph), 413 (M - O-CH 2 -Ph), 399 (M - CH 2 -O-CH 2 -). Ph), 324 (M - (O-CH 2 -Ph and O-TMS)), 91 (-CH 2 -Ph), 73 (TMS).

The optical purity of the product was analyzed chromatographically using 20 chiral HPLC analysis as well as by determining the optical rotation angle. HPLC (Chiralcel OD, 5% 2-propanol / hexane, 0.9 ml / min, 254 nm): ee> 95%; [α] D -1.54 ° ± 0.08 (CHCl 3).

The reaction mixture containing vinyl stearate and mono- and distearylated benzylglycerols could also be further processed by crystallizing the products apart.

By dissolving the mixture in 2.5 ml of isopropyl acetate and 0.6 ml of absolute ethanol and cooling the solution at -18 ° C overnight, crystallized distearylated benzylglycerol could be isolated in 95% pure, 85% yield. Thus, this crystallization method is only suitable when it is desired to isolate the di-product for further reactions. Correspondingly, suitable crystallization conditions for the selective crystallization of the monoproduct could not be established.

12,92843

Example 2

Optically active (R) -1,2-distearoyl-3-benzyloxy-propane The starting material was the optically active (R) -1-stearoyl-3-benzyloxy-2-propanol obtained in Example 1, which was chemically stearylated with (R) -1, To 2-distearoyl-3-benzyloxypropane as follows: Stearic acid (32.2 mg, 0.139 mmol) in 5 mL of dichloromethane under argon was added to a solution of dichloromethane (5 mL) containing 50.8 mg (0.139 mmol) of optically active (R) -1-stearoyl. -3-benzyloxy-2-propanol at 0 ° C with stirring. The reaction was initiated by the addition of a dichloromethane solution (5 mL) containing 60.75 mg (0.361 mmol) of dicyclohexylcarbodiimide and 12.5 mg (0.125 mmol) of 4-dimethylaminopyridine. The mixture was stirred for 5 minutes at 0 ° C, then warmed to room temperature and stirred for 2.5 hours. The reaction mixture was filtered and the solvent was evaporated off. The yield was 89.3 mg, 90%. The crude product was crystallized from a solution of isopropyl acetate (75%) in ethanol (25%) at -18 ° C. The results of 1 H NMR and GC-MS analyzes corresponded to the analyzes of the distearylated product isolated above.

[α] D -4.85 ° ± 0.10 (CHCl 3).

25 Example 3

Optically active (S) -1,2-distearoyl-3-propanol

The benzyl group of the optically active (S) - or (R) -1,2-distearoyl-3-benzyloxypropane prepared according to Example 1 or 2 was removed by hydrogenation.

30 The apparatus was carefully deaerated before starting the reaction. A solution of 81.9 mg (0.115 mmol) of optically active (S) -1,2-distearoyl-3-benzyloxypropane in 25 ml of tetrahydrofuran (anhydrous) was hydrogenated in the presence of a palladium catalyst (13 mg, 11 13 92843 10% Pd / C) at room temperature (1 atm). When the hydrogen absorption was complete after a reaction time of 90 minutes, the suspension was filtered and the catalyst was washed with diethyl ether. the combined organic fractions were concentrated in vacuo.

The crude product was crystallized from a solution of chloroform (0.9 ml) in petroleum ether (2.7 ml) at -18 ° C. Yield 64.7 mg (79%). By crystallization from purified (S) -1,2-distearoyl-3-propanol, a Mosher ester derivative was prepared according to the literature (3), and the optical purity of the hydrogenated intermediate was determined from the 1 H NMR spectrum and the optical rotation angle. 1 H NMR (400 MHz, CHCl 3): ε> 95%; [α] D -2.65 ° ± 0.11, (CHCl 3), ee> 95%, in writing. (3), (16), (18).

Example 4 1,2-Distearoyl-sn-glycero-3-phosphocholine

A solution of 11.3 mg (0.112 mmol) of triethylamine abs. in benzene (0.1 mL) was added dropwise to a solution of the above prepared optically active (S) -1,2-distearoyl-3-propanol (64.7 mg, 20.104 mmol) and 2-chloro-2-oxy-1,2,2 -dioxaphospholane (15.5 mg, 0.123 mmol) in benzene (0.6 mL) at 0-5 ° C with stirring. Stirring was continued at room temperature overnight, after which the mixture was filtered and the filtrate was concentrated in vacuo. The crude product was dissolved in 15 ml of diethyl ether and the product was crystallized at -18 ° C. The isolated product was dissolved in acetone (10 mL) and transferred to a cooled pressure vessel. To a sealed pressure vessel was added trimethylamine (anhydrous, 0.3 mL) and the reaction mixture was stirred at 65 ° C for 24 h. After cooling, the separated white precipitate was filtered and washed with diethyl ether. After flash chromatographic purification (silica gel column, eluent first CHCl 3 -CH 3 OH = 3/2, then CHCl 3 -CH 3 OH-H 2 O * 65/25/4), the product 58 mg (monohydrate, 70% yield) was isolated. The results of 1 H NMR analysis 35 corresponded to those reported in literature (5), (21).

14 92843

The optical purity of the compound was determined by the optical rotation angle. [α] D + 6.5 ° ± 0.4 (CHCl 3 -CH 3 OH = 1/1).

There are a number of different angles of rotation in the literature for optically pure 1,2-distearoyl-sn-glycero-3-5 phosphocholine (CHCl 3 -CH 3 OH = 1/1), e.g. [α] D + 6.95 ° (5), 6.80 ° (Sigma Chemical Co.), + 6.4 ° (22).

The following page shows a diagram of the method described in the above examples and the reactions of the intermediates obtained therefrom to optically active phospholipids.

Il 15 92843

References 1. Eibl, H. Chem. Phys. Lipids 1980, 26, 405 2. Lok, C.M .; Ward, J.P .; van Dorp, D.A. Chem. Phys. Lipids 1976, 16, 115 5 3. Burgos, C.E., Ayer, D.E .; Johnson, R.A. J. Org. Chem.

1987, 52, 4973 4. Wang, Y.F .; Lalonde, J.L .; Momongan, M .; Bergbreiter, D.E .; Wong, C.H. J. Am. Chem. Soc. 1988, 110, 7200 10 5. Ali, S .; Bittman, R. J. Org. Chem. 1988, 53, 5547 6. Baba, N .; Yoneda, K .; Tahara, S .; Iwasa, J .; Kaneko, T .; Matsuo, M. J. Chem. Soc. Chem. Commun. 1990, 1281 7. Fairbourne, A .; Gibson, G.P .; Stevens, D.W. J. Chem.

Soc. 1931, 445 15 8. Swern, D .; Jordan, E.F. Organic Synthesis; Wiley: New

York, 1963; Coll. Vol. IV, pp. 977 - 980 '9. Baba, N .; Tahara, S .; Yoneda, K .; Iwasa, J. Chemistry

Express, 1991, 6, 423 10. Guo, Z.W .; Wu, S.H .; Chen, C.S .; Girdaukas, G .; Sih, 20 C.J. J. Am. Chem. Soc. 1990, 112, 4942 11. Howe, R .; Shanks, R.G. Nature, 1966, 210, 1336 12. Demopoulos, C.A .; Pinhard, R.N .; Hanahan, D.J. J. Biol. Chem. 1979, 254, 9355 13. Delfino, J.M .; Schreiber, S.L .; Richards, F.M.

25 Tetrahedron Lett., 1987, 28, 2327 92845 16 14. Phuong, N.H .; Thung, N.T .; Chabriev, P. C.R. Acad. It. Paris, Serie C, 1976, 283, 229 15. Miyazaki, H .; Ohkawa, N .; Nakamura, N .; Ito, T .; Sada, T .; Oshima, T .; Koike, H. Chem. Pharm. Bull., 1989, 37, 5 2379 16. Ioannou, V .; Dodd, G .; Golding, B. Synthesis 1979, 939 17. Mitsunobu, 0 Synthesis 1981, 1 18. Sowden, J.C .; Fisher, H.O.L. J. Am. Chem. Soc. 1941, 10 63, 3244 19. Still, W.C .; Kahn, M .; Mitra, A. J. Org. Chem. 1978, 43 (14), 2923 20. Bosetti, A .; Bianchi, D .; Cesti, P .; Golini, P .;

Spezia, S. J. Chem. Soc. Perkin Transl. 1992, 2395 15 21. Laube, T; Kurreck, H. J. Labell. Comp. Radiopharm.

1983, 20 (1), 111 22. Patel, K.M .; Morrisett, J.D .; Sparrow, J.T. J. Lipid.: Res. 1979, 20, 674 23. Baba et al., Indian Journal of Chemistry 31B (1992), 20 824-827 24. Ghisalba et al., Reel. Trav. Chim. Pays-Bas 110 (1991), I 263-264 25. Wang et al., J. Org. Chem. 53 (1988), 3127-3129 26. Murata et. ai, Chem. Pharm. Bull. 37 (1989), 2670-25672

II

Claims (2)

17 92843 PATENT CLAIM ET A process for the preparation of optically active 1-monoacylglycerol or 1,2-diacylglycerol derivatives of the general formula i? X \ A \ 5 Rrc-cr A Ό-Χ (I) Hu ^ H f / \ // \? I / \ Α Rj-CO 'NO-X or Rj-CC / J ^ 0-XW ^ 3- <j-R2 R2 -jj-0 * 10 0 0 (IIa) (Hb) wherein X is an easily removable protecting group Y or hydrogen, wherein the protecting group Y may be unsubstituted or substituted benzyl or trityl or a silyl group Si (R) 3, wherein the R substituents may be identical or different and are alkyl or aryl groups; R 1 and R 2, which may be the same or different, are a C 3 -C 28 alkyl, a C 2 -C 28 alkenyl or alkynyl group or at the same time both a · * alkenyl and an alkynyl group, wherein the number of double or triple bonds may be one or more that a racemic compound of formula (V) is reacted with an anhydride RjCOOOCRj or a compound of formula (III) wherein Rj in the presence of a lipase enzyme acting as a catalyst olf / NXNJ (N) N (\) Y (V) • OH is the same as before and R 3 is a vinyl, trifluoroethyl or isopropenyl group, either 18 92843 a) to a compound of formula (I) wherein X is a protecting group Y and which compound is isolated from the reaction mixture and optionally i) hydrogenated to remove the protecting group Y, or ii) esterification with an acid R 2 COOH wherein R 2 is the same as before and may be the same as R 1 or different to give a compound of formula (IIa) or (IIb) wherein X is s a protecting group Y, from which the compound is optionally deprotected by hydrogenation, · or b) a compound of formula (IIa) wherein X is a protecting group Y and R 2 = Rt, after which the resulting compound is optionally catalytically hydrogenated to remove the protecting group Y 15. A process for the preparation of optically active compounds of formula (I), (IIa) or (IIb) according to claim 1, wherein R 1 and R 2, which may be the same or different, are C 14 to C 25 alkyl, C 14 to C 20-20 alkenyl or -alkynyl group or at the same time both an alkenyl and an alkynyl group in which the number of double or triple bonds may be one or more characterized in that the lipase enzyme is lipase PS or lipase AK and that R3 is vinyl. ‘* 25» tl 19 92843 For use in the manufacture of optically active 1-monoacylglycerols or 1, 2-diacylglycerols, 5. AAv, Rj-C-O ^ X ND-X (I) Ha?, L / \ // \ R ^ C-O 'X 0-X or Rj-C-O ^ 0-X 10 Ta ^> - C-R2 R2-C- (7 O 0 (Ila) (Hb) from X is a group Y in the case of a group or a group of compounds which is a property of 15 or substituted by benzyl or trityl or en a silyl group Si (R) 3, wherein the R substituent is a substituent or an alkyl or an aryl group; R1 and R2 are a substituent or an alkyl or a C1-C28-alkyl, C2-C28-alkenyl or -alkynyl group; the same number of alkenyl- and 20 alkynylgrupp, där dubbel- eller trippelbindningarnas mängd kan vara en eller flera, kännetecknat därav, att man omsätter en racemisk förening med formeln (V) 0Η ^ Χγ / ^ Νχ0Υ (V) OH 25. närvaro av ett lipasas , a funger with a catalyst, with an anhydride R 2 O 2 CR or an ester (III), a compound of the formula R 1 C 10 R 3 (III), or an R 3 or a mixture of vinyl, trifluoroethyl or isopropenyl, and ) to the first of the formulas (I), with X and 5 groups Y, and with the same isolation and in the reaction group and optionally i) hydrated for the first time in group Y, or ii) for the group consisting of R2C00H, then R2 is the word somewhere in the range and may be replaced by R1 or olvid, varvid 10 man erhäller en förening med formeln (Ila) or (lib), where X is a group Y, in which case the group is a genomic hydration, or (b) an X group is a group Y and R2 = Rlf varefter den a total of 15 eventual hydrolytic catalysts are used for the group Y. 2. A compound according to claim 1 for the preparation of an optically active compound according to formulas (I), (IIa) or (IIb), R1 and R2, which may be a residue or an oil, which is C14-C25-alkyl, C14-C25- alkenyl or -alkynyl group or velvet-bonded alkenyl- and alkynylgrupp, där dubbel- eller trippelbindningarnas mängd kan vara en eller flera, kännetecknat därav, att lipasenzymet är lipas *. PS or lipas AK and att R3 är vinyl. tl