WO1994019309A1

WO1994019309A1 - A novel method for the preparation of optically active compounds as well as novel end products

Info

Publication number: WO1994019309A1
Application number: PCT/FI1994/000066
Authority: WO
Inventors: Eija MÄENSIVU; Jan Näsman
Original assignee: Maeensivu Eija; Naesman Jan
Priority date: 1993-02-25
Filing date: 1994-02-18
Publication date: 1994-09-01
Also published as: FI92843B; FI92843C; FI930842A0; AU6110094A

Abstract

The invention relates to a method for the production of optically active glycerol derivatives having general formula (I), (IIa) or (IIb) where X represents an easily removable protecting group Y or a hydrogen atom, the protecting group Y being an unsubstituted or a substituted benzyl or trityl or a silyl group Si(R)3 where the substituents R, either similar or different, are alkyl or aryl groups; R1 and R2, which may be similar or different, are a C1 - C28-alkyl, C2 - C28-alkenyl or alkynyl group or at the same time both an alkenyl and an alkynyl group, with one or several double or triple bonds. According to the invention, a racemic compound having a formula according to (V) is reacted, in the presence of a catalytical lipase enzyme, with anhydride R1COOOR1 or with a compound (III) having the formula R1COOR3 where R1 is the same as above and R3 a vinyl, trifluoroethyl or isopropenyl group. The invention also relates to new intermediate products having formulas according to (I) or (II).

Description

A NOVEL METHOD FOR THE PREPARATION OF OPTICALLY

ACTIVE COMPOUNDS AS WELL AS NOVEL END PRODUCTS.

The invention relates to a novel method for the production of optically active glycerol derivatives and to new

optically active glycerol derivatives.

The new optically active glycerol derivatives according to the present invention are useful starting materials for the production of important optically active

glycerophospholipids. Further, the new optically active glycerol derivatives according to the invention are useful starting materials for the production of therapeutically important platelet activating factors (PAF) and beta- blockers.

Phospholipids comprise a vast group of compounds, the most important of them being derivatives of L-phosphatidic acid, i.e. phosphoglycerides, also called glycerophospholipids. L-phosphatidic acid has the formula

Phosphate esters of L-phosphatidic acid having the general formula

where R and R' represent acyl groups and R'' an amino substituted alkyl group, are important phospholipids. Glycerophospholipids are natural compounds and important components of the cell membranes of living organisms.

Glycerophospholipid molecules are amphipathic, i.e. they have a lipophilic moiety consisting of long hydrocarbon chains, and a dipolar hydrophilic moiety consisting of a phosphate group. The glycerophospholipids form, in certain solutions, vesicles whose wall consists of a

glycerophospholipid bilayer, with the lipophilic

hydrocarbon chains of both molecular layers projecting inwards into the membrane, while the hydrophilic groups of the molecules are directed towards each surface of the wall. Such a bilayer is capable of selectively regulating the permeability of the wall to different types of

substances. Liposomes, used for instance for the release of different types of drugs, consist of one or several

glycerophospholipid bilayers.

In order for a glycerophospholipid to be able to form the desired bilayers it is important that the molecule be the correct stereoisomer. Natural glycerophospholipids have the characteristic of being pure stereoisomers and not

racemates.

An important natural glycerophospholipid, found in the human basophilic cells, is the platelet-activating factor (PAF). This compound (1-O-alkyl-2(R)-acetyl-sn-glycero-3- phosphocholine) has the formula

where R represents a straight alkyl chain having 16 or 18 carbon atoms. The major natural phospholipids of the glycerophospholipid type are the lecithins, which are mainly prepared from egg yolk, bovine brain, red blood cells and soya beans. The lecithins are used for various purposes, primarily as emulsifiers in foods. Natural lecithins are mixtures of different glycerophospholipids, having typically in a compound according to formula (B), R = saturated C₁₆ - C₁₈ acyl group; R' = unsaturated C₁₆ - C₂₀ acyl group, and R'' = choline group CH₂CH₂N⁺(CH₃)₃. The glycerophospholipids intended for the release of medicinal drugs must be, however, both chemically and optically pure compounds, not mixtures. For these purposes only synthetic glycerophospholipids can be used.

Synthetic, optically active pure stereoisomers of

glycerophospholipids are usually the products of complex processes involving several production steps. In these syntheses, for instance, several different protecting groups must be employed in order to achieve a selective production of the desired derivatives and to prevent isomerization of the acyl glycerol intermediate. The major difficulty in the syntheses of glycerophospholipids

consists in the production of a pure optically active glycerol derivative and in the maintenance of the optical activity of the said glycerol derivative during the many steps of the synthesis. There have been reported total syntheses of glycerophospholipids, consisting of 6 - 14 steps, by the application of the asymmetric epoxidation method of Sharpies (3), the starting compounds being D- mannitol (1), L-serine (2) or allyl alcohols. As an

alternative to the above-mentioned methods there have also been descriptions in the literature of enzymatic

stereoselective acylation of prochiral glycerol derivatives using short-chain acyl donors, but the purity of the optically active stereoisomers has been only 96% at the best (4), being dependent on the enzyme used and on the solvent conditions. According to the most recent publications, it has been possible to reduce the number of the reaction steps to five, but in these syntheses either an expensive pure optically active starting material (5) was used or the starting material itself was synthesized in a multi-step reaction (6). In addition, the production strategy employed only allows the production of

phospholipids containing symmetric fatty acid chains (5).

The objective of the present invention is to overcome the above-mentioned problem and to achieve a novel production method having no such disadvantages, for the synthesis of optically active glycerophospholipids.

The invention relates to a method for the production of optically active glycerol derivatives with the general formula

in which X represents an easily removable protecting group Y or a hydrogen atom, protecting group Y being either an unsubstituted or a substituted benzyl or trityl group or a silyl group Si(R)₃, where the substituents R may be either similar or different alkyl or aryl groups; R₁ and R₂, similar or different, represent a C₁ - C₂₈ alkyl, C₂ - C₂₈ alkenyl or alkynyl group or at the same time an alkenyl and an alkynyl group, having one or several double or triple bonds. According to the invention, a racemic compound having a formula according to (V)

is reacted, in the presence of catalytic lipase enzyme, with anhydride R₁COOOCR₁ or with compound (III) having the formula R₁COOR₃ (III), where R₁ is the same as above and R₃ is a vinyl, trifluoroethyl or isopropenyl group, to form either a) a compound having a formula according to (I) where X is a protecting group Y, said compound being isolated from the reaction mixture and possibly alternatively

i) hydrogenated to remove protecting group Y or

ii) esterified with an acid R₂COOH where R₂ is the same as above and may be either similar to R₁ or different, giving a compound according to formula (Ha) or (lib) where X is protecting group Y, said protecting group Y being removed if desired from the said compound by hydrogenation, or b) a compound having a formula according to (Ha) where X is a protecting group Y and R₂ = R₁, after which the resulting compound may be catalytically hydrogenated to remove protecting group Y.

Suitable substituents in the benzyl or trityl protecting groups are for instance a lower alkyl, a lower alkoxy or a nitro group.

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

The invention also relates to optically active glycerol derivatives with the general formula

where Y represents an easily removable protecting group, which may be an unsubstituted or a substituted benzyl or trityl group or a silyl group Si(R)₃ where the substitutes R may be similar or different alkyl or aryl groups; R₁ and R₂, similar or different, are a C₁₄ - C₂₅ alkyl, a C₁₄ - C₂₅ alkenyl or alkynyl group or at the same time an alkenyl and an alkynyl group having one or more double or triple bonds.

In the above-mentioned formulas (I) and (II) X is

preferably a benzyl group and R₁ and R₂ are preferably similar groups.

There is known in prior art a compound corresponding to formula (I), in which compound R₁ is a C₁₅H₃₁ alkyl or a C₁₇ alkenyl group. There is a mention in the literature (16) of an optically active 1-stearoyl-3-benzyloxy-2-propanol, whose sterochemistry, however, was not specified. Among compounds having a formula according to (II), such

compounds are known where R₁ or R₂ is a straight C₁₅H₃₁ alkyl chain or a straight C₁₇H₃₅ alkyl chain.

Compounds according to formulas (I) and (II), which the present invention relates to, are useful starting materials for the production of valuable glycerophospholipid

compounds according to formula (IV)

where R₁ and R₂, which may be similar or different, are preferably a C₁₄ - C₂₅ alkyl, a C₁₄ - C₂₅ alkenyl or alkynyl group, or at the same time an alkenyl and an alkynyl group, having one or several double or triple bonds, and where R₄ is -CH₂CH₂N⁺(CH₃)₃, -CH₂CH₂N⁺H₃ or -CH₂-CH(OH) -CH₂ (OH). A compound having a formula according to (Ha) or (lib)

where R₁ and R₂ are as above is reacted with a phosphorus reagent such as phosphorus oxychloride or 2-chloro-2-oxy- 1,3,2-dioxaphospholane, yielding a compound having a formula according to (IV).

For the production of liposomes, glycerophospholipids having similar R₁ and R₂ and containing 14 - 25 carbon atoms are the most suitable.

In the method of the present invention for the production of a glycerol derivative according to formulas (I) or (II), the starting material employed, a racemic compound having a formula according to (V)

can be prepared by a single-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 production of vinyl and trifluoroethyl stearates has been described in references (8) and (9), respectively, and the yields are 60% and 83%, respectively. An acid anhydride also makes a suitable acyl donor (20). In the esterification catalyzed by lipase enzyme only vinyl and trifluoroethyl stearate have been tried as acyl donors, and of these, the vinyl derivative gave more reproducible results. Reaction times and the amount of enzyme needed are dependent on the type of the acyl donor, and they must be optimized for each case. Enantioselective acylation, catalyzed by lipase enzyme, of a racemic diol is performed according to the principle of so-called sequential resolution (10), which yields as final products either optically pure 3-benzyloxy-2-propanol acylated in position 1 or 3-benzyloxypropane acetylated in positions 1 and 2, depending on reaction time.

In sequential resolution the principle of synergy between enantioselective reaction and kinetic resolution is

applied. The method is based on premises of irreversibility of the reactions and non-inhibition of the final products. It is advisable first to form a general idea about the kinetics of each enzymatic transformation in question in order to allow optimization of the chemical yield and optical purity of the desired chiral end product. The kinetics of biocatalytic acylation is affected for instance by the activity of the particular batch of enzyme and the amount of enzyme.

The lipase-catalyzed reaction between the racemic compound according to formula (V) and the above-mentioned reagents R₁COOOR₁ or R₁COOR₃ yields optically pure 1,2-diacylated derivative according to formula (Ila) or optically pure 1- monoacylated derivative according to formula (I), depending on reaction time. The monostearylated product is formed in a rather non-selective manner in the first step. The proper resolution is achieved in the second acylation step, when the (S)-monostearylated enantiomer reacts to yield the distearylated product with considerably greater rapidity than the (R) form.

The intermediate (Ila) synthesized according to the present invention can be used for easy production of phospholipids having a symmetrical fatty acid composition. (R) or (S) phospholipids having an asymmetrical fatty acid composition can be synthesized using compound (I) as starting material. The direct chemical acylation of intermediate (I) in position 2 with the desired fatty acid by a known method (13) yields (S) phospholipids after known steps (14), (15). By performing an inversion acylation (17) of the Mitsunobu type of intermediate (I) with the desired fatty acid and complementing the synthesis by known methods (14), (15), (R) phospholipids can be prepared having as a result an asymmetric fatty acid composition. In Mitsunobu inversion the intermolecular dehydration between the alcohol and the carboxylic acid is achieved by treating the mixture with diethylazodicarboxylate and triphenylphosphine. As the reaction proceeds in mild, neutral conditions, a

practically complete inversion of the configuration of the alcohol-hydroxyl group ensues.

The invention will be described in the following section with the aid of concrete examples, which are not limiting to the invention. Example 1

Optically active (R)-1-stearoyl-3-benzyloxy-2-propanol and optically active (S)-1,2-distearoyl-3-benzyloxypropane

These compounds were prepared by enzyme-catalyzed regio and stereoselective acylation. Two reactions were

initiated, one of which was terminated when optimal

conditions for enantiomerically pure monostearylated glycerol derivative were established. The second reaction was terminated when optimal conditions for enantiomerically pure distearylated glycerol derivative were established. The analysis was based on the detection of the optically active isomers of monostearylated benzyl glycerol by chiral phase HPLC (Chiralcel OD, hexane/2-propanol = 95/5, 0.9 ml/min, 254 nm).

The reaction vessel was flame-dried under argon gas. 50 mg (0.275 mmol) of (±)-3-benzyloxy-1,2-propanediol was

dissolved in dry di-isopropyl ether (2.5 ml, the solvent was dried with a molecular sieve). 196 mg (0.632 mmol) of vinyl stearate was added. The reaction was started by adding 50 mg of lipase (Lipase Amano PS, Pseudomonas cepatia) into the clear solution. The suspension was shaken in room temperature (22°C) at 400 rpm for several hours, and the reaction was monitored by chiral HPLC. Enantiomerically pure monostearylated benzyl glycerol was isolated after 505 min reaction time, and enantiomerically pure distearylated benzyl glycerol was isolated from the second reaction vessel after 385 min reaction time.

When the reaction had advanced sufficiently, the enzyme was removed by filtering and the solvent was evaporated in a vacuum evaporator. Surplus vinyl stearate was separated from the mono- and distearylated benzyl glycerols,

respectively, with flash chromatography (19) in a silica gel column (25 g of silica gel). From the reaction mixture, from which optically pure (S)-1,2-distearoyl-3- benzyloxypropane was to be isolated, the product was eluted with 5% ethyl acetate/hexane solution, giving a yield of 81.9 mg (42%) of the distearylated product. The results of 1H-NMR and GC-MS analyses were comparable to those in the literature (3), (16). The optical purity of the compound was determined after H-NMR and polarometric results. For the ¹H-NMR analysis the benzyl protection group was removed from the compound as described in example 3, after which a Mosher ester derivative was formed of the said compound, as described in the literature (3). ¹H-NMR (400 MHz, CHCl₃): ee >95%; [α]_D + 4.61° ± 0.05 (CHCl₃).

From the reaction mixture, from which optically pure (R)- l-stearoyl-3-benzyloxy-2-propanol was to be isolated, the product was eluted with 20% ethyl acetate/hexane solution, giving a yield of 50.8 mg (41%) of the monostearylated product. ¹H-NMR and GC-MS confirmed the structure of the compound. ¹H-NMR (400 MHz, CHCl₃): δ(m, 5 H, C₆H₅), 4.56(s, 2 H,

O-CH₂-Ph), 4.17(m, 2 H, CH₂-OCO), 4.04 (m, 1 H, CH(OH)), 3.53 (m, 2 H, CH₂-O-CH₂Ph), 2.48 (s, 1 H, OH), 2.32(t, 2 H, CH₂CO), 1.60 (m, 2 H, CH₂(CH₂)₁₄), 1.25(m, 14 H, CH₂), 0.88 (t, 3 H, CH₃).

MS (EI+): m/z 520 (M+), 505(M - CH₃), 429(M - CH₂-Ph), 413(M - O-CH₂-Ph), 399(M - CH₂-O-CH₂-Ph), 324(M - (O-CH₂-Ph ja O- TMS)), 91(-CH₂-Ph), 73(TMS). The optical purity of the product was analyzed

chromatographically by chiral HPLC analysis and by

determining optical rotation. HPLC (Chiralcel OD, 5% 2- propanol/hexane, 0.9 ml/min, 254 nm) : ee >95%; [α]_D - 1.54° + 0.08 (CHCl₃). The reaction mixture containing vinyl stearate and the mono- and distearylated benzyl glycerols could be further treated to separate the products by crystallization. After dissolving the mixture in 2.5 ml of isopropyl acetate and 0.6 ml of absolute ethanol and freezing the solution in -18°C overnight crystallized distearylated benzyl glycerol could be isolated in 95% purity with a yield of 85%. This crystallization method is only suitable when the purpose is to isolate the disubstituted product for further reactions . Suitable crystallization conditions for the selective crystallization of the mono product, respectively, could not be established.

Example 2

Optically active (R)-1,2-distearoyl-3-benzyloxypropane The starting material was the optically active (R)-1- stearoyl-3-benzyloxy-2-propanol obtained in Example 1, which compound was chemically stearylated to (R)-1,2- distearoyl-3-benzyloxypropane in the following manner:

Stearic acid (32.2 mg, 0.139 mmol) in 5 ml of

dichlormethane was added in argon atmosphere to 5 ml of a solution of dichlormethane containing 50.8 mg (0.139 mmol) of optically active (R)-1-stearoyl-3-benzyloxy-2-propanol, at 0°C under stirring. The reaction was started by adding 5 ml of a dichlormethane solution containing 60.7 mg (0.361 mmol) of dicyclohexyl carbodiimide and 12.5 mg (0.125 mmol) of 4-dimethyl aminopyridine. After stirring for 5 min at 0°C the mixture was warmed to room temperature and stirred for 2.5 hours. The reaction mixture was filtered and the solvent removed by evaporation. The yield was 89.3 mg, 90%. The raw product was crystallized from isopropyl acetate (75%) - ethanol (25%) solution at -18°C. The results from ¹H-NMR and GC-MS analyses were comparable to the analyses of the distearylated product isolated above. [α]_D -4.85° ± 0.10 (CHCl₃). Example 3

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

From the optically active (S)- or (R)-l,2-distearoyl-3- benzyloxypropane prepared according to Example 1 or 2 the benzyl group was removed by hydrogenation. The equipment was carefully deaerated before starting the reaction. The solution, which contained 81.9 mg (0.115 mmol) of optically active (S)-1,2-distearoyl-3-benzyloxypropane in 25 ml of tetrahydrofurane (anhydrous), was hydrogenated in the presence of a palladium catalyst (13 mg, 10% Pd/C) at room temperature (1 atm). After complete absorption of hydrogen, after 90 min reaction time, the suspension was filtered and the catalyst washed with diethyl ether. The combined organic fractions were concentrated in vacuo. The raw product was crystallized from a chloroform (0.9 ml) - petroleum ether (2.7 ml) solution at -18°C. The yield was 64.7 mg (79%). From the (S)-1,2-distearoyl-3-propanol purified by crystallization a Mosher ester derivative was prepared according to the literature (3), and ¹H-NMR

spectrum together with optical rotation were used to determine the purity of the hydrogenated intermediary product. ¹H-NMR (400 MHz, CHCl₃): ee >95%; [α]_D -2.65° ± 0.11, (CHCl₃), ee >95%, literature (3), (16), (18).

Example 4

1,2-distearoyl-sn-glycero-3-phosphocholine

A solution containing 11.3 mg (0.112 mmol) of triethyl amine in absolute benzene (0.1 ml) was added dropwise to a solution containing the optically active (S)-1,2

distearoyl-3-propanol (64.7 mg, 0.104 mmol), prepared as described above, and 2-chloro-2-oxy-1,3,2-dioxaphospholane (15.5 mg, 0.123 mmol) in benzene (0.6 ml) at 0 - 5°C under stirring. Stirring was continued overnight at room

temperature, after which the solution was filtered and the filtrate concentrated in vacuo. The raw 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 into a refrigerated

pressurized vessel. Triethyl amine (anhydrous, 0.3 ml) was added into the closed pressurized vessel and the reaction mixture was stirred for 24 h at 65°C. After refrigeration, the white precipitate was filtered and washed with diethyl ether. After flash-chromatographic purification (on a silica gel column, the eluent being first CHCl₃-CH₃OH = 3/2, then CHCl₃-CH₃OH-H₂O = 65/25/4) 58 mg of the product

(monohydrate, yield 70%) was isolated. The results of ¹H- NMR analysis were comparable to those found in the

literature (5), (21). The optical purity of the compound was determined by optical rotation. [α]_D +6.5° ± 0.4 (CHCl₃- CH₃OH = 1/1). In the literature several values of optical rotations are found for optically pure 1,2-distearoyl-sn- glycero-3-phosphocholine (CHCl₃-CH₃OH = 1/1), for instance [α]_D + 6.95° (5), 6.80° (Sigma Chemical Co.), + 6.4° (22). A scheme is shown on the following page of the method described in the examples above and of the reactions of the intermediates prepared according to the said method, to form optically active phospholipids.

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 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, CH. J. Am. Chem. Soc. 1988, 110, 7200 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 8. Swern, D.; Jordan, E.F. Organic Synthesis; Wiley: New York, 1963; Coll. Vol. IV, s. 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, CJ. J. Am. Chem. Soc. 1990, 112, 4942

11. Howe, R.; Shanks, R.G. Nature, 1966, 210, 1336

12. Demopoulos, CA.; Pinhard, R.N.; Hanahan, D.J. J. Biol. Chem. 1979, 254, 9355

13. Delfino, J.M.; Schreiber, S.L.; Richards, F.M.

Tetrahedron Lett., 1987, 28, 2327 14. Phuong, N.H.; Thung, N.T.; Chabriev, P. CR. Acad. Sc. 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, 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, 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 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

Claims

1. A method for the production of optically active glycerol derivatives having the general formula

where X represents an easily removable protecting group Y or a hydrogen atom, where the protecting group Y can be either an unsubstituted or a substituted benzyl or trityl or a silyl group Si(R)₃, having similar or different substituents R, which can be alkyl or aryl groups; R₁ and R₂, which can be similar or different, represent a C₁ - C₂₈ alkyl, C₂ - C₂₈ alkenyl or alkynyl group or at the same time both an alkenyl and an alkynyl group, with one or several double or triple bonds, characterized by reacting a racemic compound having a formula according to (V)

in the presence of catalytic lipase enzyme, with anhydride R₁COOOCR₁ or compound (III) having the formula R₁COOR₃ (III) where R₁ is the same as above and R₃ is either a vinyl, trifluoroethyl or isopropenyl group, in order to form either a) a compound having a formula according to (I) where X is a protecting group Y, the said compound being isolated from the reaction mixture and possibly alternatively

i) hydrogenated to remove the protecting group Y or ii) esterified with acid R₂COOH where R₂ is the same as above and can be either similar or different to R₁, which gives a compound having a formula according to (Ila) or (lIb) where X is protecting group Y, from which compound the protecting group Y can be removed by hydrogenation, if desired, or b) a compound having a formula according to (Ila) where X is protecting group Y and R₂ = R₁, after which the resultant compound may be hydrogenated catalytically to remove protecting group Y.

2. A method according to claim 1 for the preparation of optically active compounds having formulas according to

(I), (Ila) or (lIb) where R₂ and R₂, which may be similar or different, represent a C₁₄ - C₂₅ alkyl, C₁₄ - C₂₅ alkenyl or alkynyl group or at the same time both an alkenyl and an alkynyl group, having one or several double or triple bonds, characterized by the lipase enzyme being lipase PS or lipase AK and R₃ being a vinyl group.

3. New optically active glycerol derivatives having a general formula according to

characterized by Y being an easily removable protecting group, which may be an unsubstituted or a substituted benzyl or trityl or a silyl group Si(R)₃ where the

substituents R may be similar or different alkyl or aryl groups; R₁ and R₂, similar or different, are C₁₄ - C₂₅ alkyl, C₁₄ - C₂₅ alkenyl or alkynyl groups or at the same time both an alkenyl and an alkynyl group, having one or several double or triple bonds, provided that a) in a compound having a formula according to (I), R₁ cannot be a C₁₅H₃₁ alkyl or a C₁₇ alkenyl group, and b) in a compound having a formula according to (II), neither R₁ nor R₂ can be a straight C₁₅H₃₁ alkyl or a straight C₁₇H₃₅ alkyl group.

4. Compounds according to claim 3 characterized by R₁ and R₂ being similar groups.