Suchergebnisse

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. ; We thank the Ministerio de Economía y Competitividad (MINECO), the Fondo Europeo de Desarrollo Regional (FEDER) (grant RTI2018-094637-B-I00), and Programación Conjunta Internacional (PCI2018-092937), through the initiative ERA CoBioTech (Tralaminol), and the DFG (FOR 1296) and the European Union's Horizon 2020 Research and Innovation Programm (Grant Agreement no. 635595) for financial support. Many thanks to Dr. Stephen Seah, University of Gulph, for providing the plasmid of hpaI. We would also like to thank Dr. Philippe Bisel and Sascha Ferlaino, University of Freiburg, for NMR measurements and constructive suggestions for the manuscript, as well as Dr. Kay Greenfield for her careful proofreading. Open Access funding enabled and organized by Projekt DEAL. ; Peer reviewed