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

Abstract

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.

Biosynthesis of cyclitols

“…A structurally related branched 12-carbon sugar, caryophyllose, 178 was isolated from the same bacterium and a putative thiamine diphosphate (TPP)-dependent enzyme is considered to be involved in the C–C bond forming reaction in the biosynthesis of the branched sugar. 179,180 Therefore, certain TPP-dependent enzymes might be involved in the carbon–carbon bond forming reaction in the caryose biosynthesis.…”