Thiamine diphosphate (ThDP) dependent enzymes are useful catalysts for asymmetric CÀ C bond formation through benzoin-type condensation reactions that result in α-hydroxy ketones. A wide range of aldehydes and ketones can be used as acceptor substrates; however, the donor substrate range is mostly limited to achiral α-keto acids and simple aldehydes. By using a unifying retro-biosynthetic approach towards acyl-branched sugars, we identified a subclass of (myco)bacterial ThDP-dependent enzymes with a greatly extended donor substrate range, namely functionalized chiral α-keto acids with a chain length from C 4 to C 8 . Highly enantioenriched acyloin products were obtained in good to high yields and several reactions were performed on a preparative scale. The newly introduced functionalized αketo acids, accessible by known aldolase-catalyzed transformations, substantially broaden the donor substrate range of ThDP-dependent enzymes, thus enabling a more general use of these already valuable catalysts.

Thiamine diphosphate (ThDP) dependent enzymes are useful catalysts for asymmetric C−C bond formation through benzoin‐type condensation reactions that result in α‐hydroxy ketones. A wide range of aldehydes and ketones can be used as acceptor substrates; however, the donor substrate range is mostly limited to achiral α‐keto acids and simple aldehydes. By using a unifying retro‐biosynthetic approach towards acyl‐branched sugars, we identified a subclass of (myco)bacterial ThDP‐dependent enzymes with a greatly extended donor substrate range, namely functionalized chiral α‐keto acids with a chain length from C4 to C8. Highly enantioenriched acyloin products were obtained in good to high yields and several reactions were performed on a preparative scale. The newly introduced functionalized α‐keto acids, accessible by known aldolase‐catalyzed transformations, substantially broaden the donor substrate range of ThDP‐dependent enzymes, thus enabling a more general use of these already valuable catalysts.