Tuning lipase enantioselectivity in organic media using solid-state buffers

The enantioselectivity exhibited by Candida antarctica lipase B (CALB) in p redominantly organic media has been studied for different enzyme protonatio n states. Alcoholysis of (+/-)-2-phenyl-4-benzyloxazol-5(4H)-one (1) using butan-1-ol as the nucleophile in low-water organic solvents was used as a m odel reaction. Using either organo-soluble bases or the newly introduced so lid-state buffers of known pK(a), the protonation state of the lipase was a ltered. By choice of the appropriate solid-state buffer or organic base, th e enantioselectivity could be selectively tuned. Both Et3N and the solid-st ate buffer pair CAPSO/CAPSO.Na were found to increase the enantioselectivit y of the reaction catalyzed by CALB and that of another lipase (Mucor miehe i). Significant differences to both the enantioselectivity and catalytic ra te were observed, especially under hydrated conditions where byproduct acid was formed.