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Lipase‐catalyzed resolution of glycerol‐based racemates
Author(s) -
Liljeblad Arto,
Vänttinen Eero,
Kanerva Liisa T.
Publication year - 1999
Publication title -
chirality
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.43
H-Index - 77
eISSN - 1520-636X
pISSN - 0899-0042
DOI - 10.1002/(sici)1520-636x(1999)11:5/6<432::aid-chir14>3.0.co;2-i
Subject(s) - chemistry , glycerol , lipase , candida antarctica , catalysis , enantiopure drug , acylation , enantiomer , ceric ammonium nitrate , organic chemistry , medicinal chemistry , enantioselective synthesis , enzyme , polymer , grafting
Enantioselectivity of six lipases toward the methanolysis of XOCH 2 CH(OCOR)CH 2 OCOR [X = trityl, 4‐methoxytrityl or 4,4′‐dimethoxytrityl and R = Me, Pr, or CH 3 (CH 2 ) 8 ] in diisopropyl ether was studied. The Pseudomonas lipases showed high enantioselectivity for the sn ‐1 position, leading to the unreacted 2,3‐di‐ O ‐acyl‐1‐ O ‐X‐ sn ‐glycerol and the produced 2‐ O ‐acyl‐3‐ O ‐X‐ sn ‐glycerol. Substrates with R = Pr (ee 95% or higher for the two enantiomers at 50% conversion) were favored over shorter or longer chain esters. A ceric ammonium nitrate method allowed the removal of X. 4‐Methoxytrityl as X led to the best result in terms of unchanged enantiopurity (ee 96%), short deprotection time and only negligible 1,3‐isomerization for the preparation of 2,3‐di‐ O ‐butyryl‐ sn ‐glycerol. The lipase‐catalyzed acylation of 2‐ O ‐butyryl‐3‐ O ‐trityl‐ sn ‐glycerol with vinyl decanoate gave 2‐ O ‐butyryl‐1‐ O ‐decanoyl‐3‐ O ‐trityl‐ sn ‐ glycerol. Interestingly, the two‐step methanolysis of the substrate (X = trityl, R = Pr) in the presence of Candida antarctica B lipase allowed the preparation of highly enantiopure 3‐ O ‐trityl‐ sn ‐glycerol (ee 94%) and enantiomerically enriched 2‐ O ‐butyryl‐1‐ O ‐trityl‐ sn ‐glycerol, the initially produced 2‐monobutyrate being practically racemic. Chirality 11:432–439, 1999. © 1999 Wiley‐Liss, Inc.