Summary
A key chiral intermediate lactol(3)[3aS (3aα,4α,7α,7aα)]-hexahydro-4,7-epoxy-isobenzofuran-1 (3H)-one was prepared for the total synthesis of a new thromboxane antagonist. The stereoselective hydrolysis of (exo,exo)-7-oxabicyclo[2.2.1]heptane-2,3-dimethanol, diacetate ester (1) to the corresponding chiral monoacetate ester (2) was carried out with lipases, among which Amano P-30 lipase from Pseudomonas sp. was most effective since it gave the desired enantiomer of monoacetate ester. A yield of 75 mol% and optical purity of >99% was obtained when the reaction was conducted in a biphasic system with 10% toluene at 5 g/l of the substrate. Lipase P-30 was immobilized on Accurel polypropylene (PP) and the immobilized enzyme was reused (five cycles) without loss of enzyme activity, productivity or optical purity. The reaction process was scaled-up to 80 1 (400 g substrate) and monoacetate (2) was isolated in 80 mol% yield with 99.3% optical purity as determined by chiral HPLC and nuclear magnetic resonance (NMR) analysis. A gas chromatography of 99.5% and specific rotation, [α]D of -7.6° was obtained. The chiral monoacetate ester (2) was oxidized to its corresponding aldehyde and subsequently hydrolyzed to give lactol (3).
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References
Ford-Hutchinson AW (1991) Innovations in drug research: inhibitors of thromboxane and leukotrienes. Clin Exp Allergy 21 Suppl 1:272–276
Guanti G, Banfi L, Narisano E, Riva R, Thea S (1986) Enzymes in asymmetric synthesis: Effect of reaction media on the PLE catalyzed hydrolysis of diesters. Tetrahedron Letters 27:4639–4642
Hamaka N, Seko T, Miyazaki T, Kawasaki A (1990) Rational design of thromboxane A2 antagonists. Adv Prostaglandin. Thromboxane Leukotriene Res 21:359–362
Jones JB (1986) Enzymes in organic synthesis. Tetrahedron 42:3351–3403
Kamphuis J, Bocosten WHJ, Broxterman QB, Hermes HFM, Balken JAM van, Meijer EM, Schoemaker HE (1990) New development in the chemo-enzymatic production of amino acids. Adv Biochem Eng Biotechnol 42:134–182
Khmelnitsky YL, Levashov AV, Klyachko NL, Martinek K (1988) Engineering biocatalytic system in organic media with low water content. Enzyme Microbiol Technol 10:710–724
Klibanov AM (1986) Enzymes that work in organic solvent. Chemtech 16:354–359
Laumen K, Schneider M (1985) Enantioselective hydrolysis of cis-1,2-diacetoxycycloalkanedimethanols: enzymatic preparation of chiral building blocks from prochiral meso-substrate. Tetrahedron Lett 26:2073–2076
Lok KP, Jakobac TJ, Jones JB (1985) Enzymes in organic synthesis preparation of enantiomerically pure exo- and endobridged bicyclic [2.2.1] and [2.2.2] chiral lactones via stereospecific horse liver alcohol dehydrogenase catalyzed oxidations of meso diols. J Am Chem Soc 107:2521–2526
Mohr P, Waespe-Sarcevic N, Tamm C (1983) A study of stereoselective hydrolysis of symmetrical diesters with pig liver esterase. Helv Chim Acta 66:2501–2511
Mosher HS, Morrison TD (1983) Current status of asymmetric synthesis. Science 221:1013–1019
Patel RN, Robison R, Szarka LJ (1990) Stereoselective enzymatic hydrolysis of 2-cyclohexyl and 2-phenyl 1,3-propanediol diacetate in a biphasic system. Appl Microbiol Biotechnol 34:10–14
Ritter JM, Doktor HS, Benjamin N, Barrow SE, Stewart-Long P (1990) On the mechanism of the prolonged action in man of GR 32 191, a thromboxane receptor antagonist. Adv Prostaglandin Thromboxane Leukotriene Res 21:351–354
Tombo GMR, Schar HP, Busquets XF, Ghisalba O (1986) Synthesis of both enantiomeric forms of 2-substituted 1,3-propanediol monoacetates starting from a common prochiral precusors, using enzymatic transformation in aqueous and in organic media. Tetrahedron Lett 21:5707–5710
Whitesides GH, Wong C-H (1985) Enzymes as catalysts in synthetic organic chemistry. Angew Chem Int Ed Engl 24:617–638
Wirz B, Schmid R, Walther W (1990) Enzymatic preparation of (R)-3-hydroxy-2-methylpropyl butyrate by asymmetric hydrolysis. In Biocatalysis, Harvard academic publication, vol. 3, p 159–167
Yamada H, Shimizu S (1988) Microbial and enzymatic processes for the production of biologically and chemically useful compounds. Angew Chem Int Ed Engl 27:622–642
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Patel, R.N., Liu, M., Banerjee, A. et al. Stereoselective enzymatic hydrolysis of (exo,exo)-7-oxabicyclo[2.2.1]heptane-2,3-dimethanol diacetate ester in a biphasic system. Appl Microbiol Biotechnol 37, 180–183 (1992). https://doi.org/10.1007/BF00178167
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DOI: https://doi.org/10.1007/BF00178167