Effect of distant groups on the enantioselectivity in kinetic resolution of sec-alcohols catalyzed by microbial lipases

Ljubović, Edina; Šunjić, Vitomir (1998) Effect of distant groups on the enantioselectivity in kinetic resolution of sec-alcohols catalyzed by microbial lipases. Croatica Chemica Acta, 71 (1). pp. 99-117. ISSN 0011-1643

PDF - Published Version
Download (176kB)

Official URL: http://public.carnet.hr/ccacaa/co981.html

Abstract

A short series of racemic phenoxyalkyl-alkycarbinols, possessing perturbing groups at different distances from the stereogenic center, was prepared. The sec-alcohols (+/-)-1-phenoxy-2-hydroxybutane (6), (+/-)-1-phenoxy-3-hydroxyhexane (11), (+/-)-1-phenoxy-4-hydroxyoctane (15) and (+/-)-1-phenoxy-5-hydroxydecane (19) were prepared. The enantioselectivity of their acetylation by vinylacetate catalyzed by microbial lipases in n-hexane was determined. The products of this acetylation were (+/-)-1-phenoxy-2-acetoxybutane (7), (+/-)-1-phenoxy-3-acetoxyhexane (12), (+/-)-1-phenoxy-4-acetoxyoctane (16), and (+/-)-1-phenoxy-5-acetoxydecane (20). The efficacy of kinetic resolution, expressed as E-value, generally diminishes with the distance of the perturbing phenoxy (R-L) and methyl (R-M) groups. Twenty lipases from commercial sources were screened for their enantioselectivity; for two lipases with broadest substrate selectivity, Geotrichum candidum (GCL) and Candida cyclindracea (CCL (S), from Sigma), non-monotonous correlation between E-value and the distance (n) of the perturbing group was observed. With GCL lipase, a remarkable turnover of enantioselectivity from preferred acetylation of (R)-enantiomers in 6, 11, 15 to (S)-enantiomer of 19 was observed, indicating that relative steric requirements of the distant perturbing groups in the latter do not control the enantioselective bias. The herewith reported results are correlated with the previously observed stereoselective acetylation of (S)-sec-alcohols (3S, 7S)-trans-3,4,5,6,9,10-octahydro-7,14,16-trihydroxy-3-methyl-1H-2-benzoxacyclotetradecene-1-one (1) and (3S,7S)-3,4,5, 6,9,10,11, 12-decahydro-7,14,16-trihydroxy-3-methyl-1H-2-benzoxacyclotetradecane-1-one (3), macrocyclic derivatives of resorcyllic acid, and also with the results of MM2 calculations for some low energy conformations.

Item Type:

Article

Uncontrolled Keywords:

pseudomonas-cepacia; organic-solvents; derivatives; model

Subjects:

NATURAL SCIENCES > Chemistry

Divisions:

Division of Organic Chemistry and Biochemistry

Projects: