EFFECT OF DISTANT GROUPS ON THE ENANTIOSELECTIVITY IN KINETIC RESOLUTION OF SEC-ALCOHOLS CATALYZED BY MICROBIAL LIPASES

A short series of racemic phenoxyalkyl-alkycarbinols, possessing pertu rbing groups at different distances from the stereogenic center, was p repared. The sec-alcohols (+/-)-1-phenoxy-2-hydroxybutane (6), (+/-)-1 -phenoxy-3-hydroxyhexane (11), (+/-)-1-phenoxy-4-hydroxyoctane (15) an d (+/-)-1-phenoxy-5-hydroxydecane (19) were prepared. The enantioselec tivity of their acetylation by vinylacetate catalyzed by microbial lip ases 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-acet oxydecane (20). The efficacy of kinetic resolution, expressed as E-val ue, generally diminishes with the distance of the perturbing phenoxy ( R-L) and methyl (R-M) groups. Twenty lipases from commercial sources w ere screened for their enantioselectivity; for two lipases with broade st substrate selectivity, Geotrichum candidum (GCL) and Candida cyclin dracea (CCL (S), from Sigma), non-monotonous correlation between E-val ue and the distance (n) of the perturbing group was observed. With GCL lipase, a remarkable turnover of enantioselectivity from preferred ac etylation 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 bi as. The herewith reported results are correlated with the previously o bserved stereoselective acetylation of (S)-sec-alcohols (3S, ydroxy-3- methyl-1H-2-benzoxacyclotetradecene-1-one (1) and (3S,7S)-3,4,5, 6,9,1 0,11, ydroxy-3-methyl-1H-2-benzoxacyclotetradecane-1-one (3), macrocyc lic derivatives of resorcyllic acid, and also with the results of MM2 calculations for some low energy conformations.