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Keywords:

  • asymmetric synthesis;
  • biocatalysis;
  • carboligation;
  • cross-coupling;
  • thiamine-dependent enzymes

Abstract

Thiamine diphosphate (ThDP) dependent enzymes catalyze the formation of acetoin (3-hydroxybutan-2-one) through one of three different pathways: homocoupling of pyruvate, homocoupling of acetaldehyde, or cross-coupling of acetaldehyde (as acceptor) and pyruvate (as donor). The enantioselectivity of the resulting acetoin is highly dependent on the particular enzyme. We established that ThDP-dependent cyclohexane-1,2-dione hydrolase (CDH) is able to form (S)-acetoin with particularly high enantioselectivity (up to 95 % ee) by all three pathways. Mechanistic studies utilizing 13C-labeled substrates revealed an unprecedented non-acetolactate pathway for the homocoupling of pyruvate, which explains the high enantioselectivity in the CDH-catalyzed formation of (S)-acetoin.