α-Keto Acid Dehydrogenases: A Chemical Model

Article abstract of DOI:10.1021/jo00322a027

A model system for the involvement of lipoic acid in α-keto acid dehydrogenase systems is described. 2-(α-Hydroxyethyl)-3-benzyl-4-methylthiazolium tetrafluoroborate (6) serves as precursor for an analogue of the thiamine-bound active aldehyde 1 in the natural system.The model active aldehyde 7 reacts with linear disulfides, yielding thiols and thioesters.The 1,2-dithiolane, methyl lipoate (14), is unreactive under model reaction conditions.The tetrahedral intermediate which would be formed from methyl lipoate (14) plus an active aldehyde analogue 19 has been generated in a nonbiomimetic fashion.The synthetic tetrahedral intermediate 17 undergoes the reverse of the biological, disulfide reductive cleavage reaction.