Resolution of a tetrahydrofuran ester by Candida rugosa lipase (CRL) and an examination of CRL's stereochemical preference in organic media

Crude lipase from Candida rugosa (CRL) is able to resolve the C3-stereoisomers of the furo[2,3b]furan building block methyl 2-methoxytetrahydrofuran-3-carboxylate 6 by alcoholysis using n-butanol in octane. The reaction is not affected by the configuration at C2. The absolute configuration of the product 7 is 3S as determined by X-ray analysis of the crystalline derivative 14. The stereochemical outcome of the reaction is compared to the active site model derived by the group of Kazlauskas (Ahmed et al., Biocatalysis 9 (1994), 209). Evidence is presented for the validity of this model for CRL-catalyzed alcoholysis, esterification and acidolysis reactions in organic media. Graphic