Coenzyme Models. 26. Facile Oxidation of Aldehydes and α-Keto Acids by Flavin as Catalyzed by Thiazolium Ion and Cationic Micelle

The reaction sequence of acyloin condensation of aldehydes which is catalyzed by N-hexadecylthiazolium bromide (HxdT) in the CTAB micelle was readily diverted by added 3-methyltetra-O-acetylriboflavin (MeFl) to the oxidation reaction to afford carboxylic acids. Similarly, the micellized thiazolium ion plus MeFl system efficiently catalyzed the decarboxylative oxidation of aliphatic a-keto acids but scarcely catalyzed that of aromatic -keto acids. In contrast, hydrophilic thiazolium ions such as N-benzylthiazolium bromide (BzlT), thiamine, and thiamine pyrophosphate (TPP) were less effective catalysts. The reactions were zero-order in MeFl and first-order in HxdT and substrates, the apparent second-order rate constants being enhanced by factors of lOMO4 in comparison to those in the nonmicellar system. On the basis of the kinetic examination and the product analysis, we proposed that the reactions involve oxidative trapping by MeFl of the intermediate formed by the rate-limiting deprotonation or decarboxylation from the HxdT-substrate adducts. This means that the intermediate of the thiazolium ion catalysis (active aldehyde) serves as substrate for the flavin oxidation. This is the first nonenzymatic example for the synergistic catalysis of flavin coenzyme and TPP coenzyme. The relevance of the reactions to biological systems (in particular, to pyruvate dehydrogenase which requires FAD and TPP as cofactors) is discussed. Since the 2-acyl group of the oxidation products (2-acylthiazolium ions) is sensitive to nucleophiles, the reaction is readily applicable to synthesis of esters from aldehydes.