Chemoenzymatic dynamic kinetic resolution of acyloins.
[Reaction: see text]. Acyloins (alpha-hydroxy ketones) are important building blocks in organic synthesis, e.g., for the total synthesis of epothilones. Optically pure acyloins can be obtained by lipase-catalyzed kinetic resolution (KR) of the racemate with, for example, Burkholderia cepacia lipase, but this process suffers from a yield limitation of 50%. To devise a dynamic kinetic resolution (DKR), we studied the racemization of two different acyloins and corresponding esters with various amine bases and ion exchangers. No combination of base and solvent was found that could selectively racemize the acyloin or corresponding ester under the conditions needed for a DKR. In contrast to bases, acidic resins (ARs) were found to racemize the acyloins selectively in n-hexane and in water. Unfortunately, the AR deactivated the lipase, preventing a one-pot DKR. Minor side reactions involving the AR, the substrate acyloin, and the vinyl ester acyl donor were also observed. However, an efficient DKR was made possible by the spatial separation of lipase and ion exchanger, with enzymatic transesterification and AR-catalyzed racemization taking place simultaneously in two compartments connected by a pump loop. The conversion of substrate alcohol was 91%, the selectivity toward the product butyrate ester 90%, and the enantiomeric excess of the (S)-product 93% ee.
Odman
Peter
P
Department of Technical Chemistry and Biotechnology, Institute of Chemistry and Biochemistry, Greifswald University, Soldmannstrasse 16, D-17487 Greifswald, Germany.
Wessjohann
Ludger A
LA
Bornscheuer
Uwe T
UT
D002384:Catalysis; D004951:Esterification; D004952:Esters / Q000737:chemistry*; D005233:Fatty Alcohols / Q000737:chemistry*; D007475:Ion Exchange Resins; D007700:Kinetics; D008049:Lipase / Q000378:metabolism*; D013237:Stereoisomerism
D004952:Esters; D005233:Fatty Alcohols; D007475:Ion Exchange Resins; C011159:acyloin; D008049:Lipase