Enantiopure derivatives of 1,2-alkanediols: Substrate requirements of lipase B fromCandida antarctica

Abstract

Efficient methods for kinetic resolution of 1-phenoxy-2-butanol, 1-phenylmethoxy-2-butanol, and 1-phenoxy-2-pentanol were developed using lipase B from Candida antarctica as catalyst. Resolutions were performed in order to investigate the substrate requirements needed to obtain a high E-value. The effect of the substrate structure on E is different for transesterifications in organic media as compared to hydrolysis. The influence of different acyl donors on the E-value was also investigated.

Biocatalytic synthesis of saphenic acid enantiomers

“…We have found earlier that n-propyl is the largest group that can fit into the stereospecificity pocket of CALB, leading to high enantioselectivity in kinetic resolutions of secondary alcohols. 19 The enantioselectivity is not to the same extent dependent on the size of the large group. CALA shows high enantioselectivity for phenyl-(2-naphthyl)-methanol (6) (one phenyl and one naphthyl group connected to the stereocenter) which is in accordance with previous reported results.…”

Factors Affecting Enantioselectivity: Allosteric Effects

“…If computer programs are used for calculating E based on several measurements, an average E will result. The E -value depends as mentioned primarily on the enzyme and the substrate, but also on the acyl donor used in acyl transfer reactions in organic solvents [13,14] . Acyl donors like activated haloalkyl esters can give high E -values, but may be reversible to some extent.…”

“…Enol esters, on the other hand, such as vinyl or isopropenyl esters, give irreversible reaction conditions, but may reduce the E -value due to acylation of amino groups of the enzyme [13] . The liberated acetaldehyde, when vinyl esters are used as acyl donors, may react with amino groups of the enzyme and, thus, reduce the selectivity [4b] , but this is not always a problem [14] . The E -value also depends on the medium in which the reaction is carried out.…”

“…In the esterifi cation of 4a a decrease in E was observed It was also surprising that the E -value in the case of ( R ) -1 -phenoxy -2 -hexanol (( R ) -5a ) increased and also dropped to the low level quickly after addition. It has been shown that 5a is esterifi ed by vinyl butanoate and CALB with almost no selectivity and with a low rate [14] . For that reason, it seems unlikely that the disappearance of the selectivity enhancement was only due to esterifi cation of the alcohol.…”

“…The effect of increasing the small substituent of 1a by one CH 2 unit as in 2a is shown in Figure 7.7 . It is evident that the reason for the decrease in E is due to a slower reaction of the faster enantiomer [14] . This is the opposite of the effect observed when the ethyl ester of 8a is changed into tert -butyl as in 9a (Scheme 7.3 ).…”