Unifying Scheme for the Biosynthesis of Acyl‐Branched Sugars: Extended Substrate Scope of Thiamine‐Dependent Enzymes

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 is mostly limited to achiral α-keto acids simple aldehydes. By using a unifying retro-biosynthetic approach towards acyl-branched sugars, we identified subclass (myco)bacterial ThDP-dependent with greatly extended range, namely functionalized chiral chain length from C4 C8. Highly enantioenriched acyloin products were obtained good high yields several performed on preparative scale. The newly introduced acids, accessible by known aldolase-catalyzed transformations, substantially broaden enzymes, thus enabling more general use these already valuable catalysts.