H. Jongejan

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

Abstract 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.

Formation of hemiacetal esters in lipase-catalysed reactions of vinyl esters with hindered secondary alcohols

Normally many lipases are efficient catalysts for the acetylation of alcohols with vinyl acetate. Unexpectedly, we found that some sterically hindered secondary alcohols react slowly to yield hem ...

Enzymatic alcoholysis of alkoxymethyl alkanoates: a possible approach for the kinetic resolution of tertiary alcohols

Abstract The pivaloyloxymethyl and butanoyloxymethyl derivatives of tert -butanol and linalool ( 1, 4 ) are readily accepted by hydrolases. Linalool derivative 4b is alcoholysed stereoselectively by Candida rugosa lipase (E=9.7).

Resolution of limonene 1,2-epoxide diastereomers by mercury(II) ions

When HgCl2 was added to a diastereomeric mixture of cis- and trans-(4S)-limonene 1,2-epoxide, the Hg(II) ions stereoselectively complexed to the cis epoxide, enabling ring opening by water. The resulting mercuric salt could be demetalated by treatment with NaBH4, giving a mixture of diastereomeric (1S,2S,4S)- and (1R,2R,4S)-diols. The remaining trans-(4S)-epoxide was obtained in >98% d.e. and 40% yield. For reactions on a larger scale, the most convenient reaction system was Hg(OAc)2 in 50% acetone/tris-HCl buffer pH 7.0. The reaction rate was affected by the pH, with pH 6-8 as optimum.

LIPASE-MEDIATED RESOLUTION OF OCTAHYDRO-3,3,8A-TRIMETHYL-1 -NAPHTHALENOL, A KEY INTERMEDIATE IN THE TOTAL SYNTHESIS OF LACTARANES AND MARASMANES

Abstract The bicyclic alcohol (1α,8aα)-1,2,3,4,6,7,8,8a-octahydro-3,3,8a-trimethyl-1-naphthalenol (±)-1 was resolved using Candida rugosa lipase-mediated esterification with vinyl acetate (E=72). The absolute configuration of the remaining isomer was determined by X-ray analysis of its 4-chloro-3-nitrobenzoate. The observed stereochemical preference of the enzyme is in line with the rule formulated by Kazlauskas et al. [Kazlauskas, R. J.; Weissfloch, A. N. E.; Rappaport, A. T.; Cuccia, L. A. J. Org. Chem. 1991, 56, 2656–2665]. The resolved alcohol is a useful chiral synthon for natural lactarane and marasmane sesquiterpenes.