Extended reaction scope of thiamine diphosphate dependent cyclohexane-1,2-dione hydrolase: From C-C bond cleavage to C-C bond ligation

07.11.2014

Loschonsky S, Wacker T, Waltzer S, Giovannini PP, McLeish MJ, Andrade SL, Müller M.

Angew Chem Int Ed Engl. 2014;53(52):14402-6

Angew Chem Int Ed Engl.            online article

ThDP-dependent cyclohexane-1,2-dione hydrolase (CDH) catalyzes the C–C bond cleavage of cyclohexane-1,2-dione to 6-oxohexanoate, and the asymmetric benzoin condensation between benzaldehyde and pyruvate. One of the two
reactivities of CDH was selectively knocked down by mutation experiments. CDH-H28A is much less able to catalyze the C–C bond formation, while the ability for C–C bond cleavage is still intact. The double variant CDH-H28A/N484A shows the opposite behavior and catalyzes the addition of pyruvate to cyclohexane-1,2-dione, resulting in the formation of a tertiary alcohol. Several acyloins of tertiary alcohols are formed with 54–94% enantiomeric excess. In addition to pyruvate, methyl pyruvate and butane-2,3-dione are alternative donor substrates for C–C bond formation. Thus, the very rare aldehyde–ketone cross-benzoin reaction has been solved by design of an enzyme variant.