Candida enantiopreference

An interesting case is the resolution of a heterohelicenediol. The very bulky racemic substrate roc-15 is resolved by lipase-catalyzed acylation with vinyl acetate in dichloromethane. Oddly enough, Candida antarctica lipase (CAL) and Pseudomonas cepacia lipase (PCL) display opposite enantiopreferences [54]. In Scheme 4.13, only the remaining substrates are shown and not the other products, the mono- and diacetates. 

It is known that enantioselectivity of enzymes depends on many different parameters such as temperature, substrate structure, reaction medium, and presence of water. Enantiopreference of enzymes can be greatly affected, even reversed, by changing the reaction solvent. Such an example was reported by Ueji et al. in 1992 for Candida cylindracea lipase-catalyzed esterification of ( )-2-phenoxy propionic acid with 1-butanol [29]. 

The fact that cmde Candida rugosa lipase occasionally exhibits a moderate selectivity particularly on a-substituted carboxylic esters could be attributed to the presence of two isomeric forms of the enzyme present in the cmde preparation [422, 423]. Both forms (denoted as fraction A and B), could be separated by Sephadex chromatography and were shown to possess a qualitatively identical (i.e., identical enantiopreference) but quantitatively different stereoselectivity... 

Dynamic resolution of various sec-alcohols was achieved by coupling a Candida antarctica lipase-catalyzed acyl transfer to in-situ racemization based on a second-generation transition metal complex (Scheme 3.17) [237]. In accordance with the Kazlauskas rule (Scheme 2.49) (/ )-acetate esters were obtained in excellent optical purity and chemical yields were far beyond the 50% limit set for classical kinetic resolution. This strategy is highly flexible and is also applicable to mixtures of functional scc-alcohols [238-241] and rac- and mcso-diols [242, 243]. In order to access products of opposite configuration, the protease subtilisin, which shows opposite enantiopreference to that of lipases (Fig. 2.12), was employed in a dynamic transition-metal-protease combo-catalysis [244, 245]. 

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