Substrate modification to increase the enantioselectivity of hydrolases. A route to optically-active cyclic allylic alcohols.

Ajay K. Gupta, Romas J. Kazlauskas

Research output: Contribution to journalArticlepeer-review

60 Scopus citations

Abstract

The esterase-catalyzed resolution of the cyclic allylic acetates-1-acetyloxy-2-cyclopentene, 1-acetyloxy-2-cyclohexene, and 1-acetyloxy-2-cycloheptene - was not enantioseleclive. We hypothesized that this inefficiency stems from the similarity in size of the substituents at the stereocenter (CH 2 CH 2 vs. CHCH). To increase the enantioselectivity, we resolved precursors to these cyclic allylic alcohols: esters of trans-2-bromocycloalkanols (C 5 , C 6 , C 7 ). These esters had a larger difference in the size of the substituents (CH 2 vs. CHBr) at the stereocenter and were efficiently resolved by both cholesterol esterase and lipase from Pseudomonas cepacia (Amano P, PCL). A synthetic-scale resolution with PCL yielded the (1S,2S)-1-butanoyloxy-2-bromocycloalkanes in >98% ee. Heating with DBU to eliminate HBr, followed by reduction with LiAlH 4 to cleave the ester, yielded the allylic alcohols: (S)-(-)-2-cyclopenten-1-ol (65% ee), (S)-(-)-2-cyclohexen-1-ol (>99% ee), and (S)-(-)-2-cyclohepten-1-ol (>98% ee).

Original languageEnglish (US)
Pages (from-to)879-888
Number of pages10
JournalTetrahedron: Asymmetry
Volume4
Issue number5
DOIs
StatePublished - May 1993

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