Symposium 14 : Invited Speaker 

The complementary and integrated chemoenzymatic processes for fine chemical syntheses

Prof. Takeshi Sugai
Keio University

Abstract

Commercially available lipases for industrial use are robust catalysts in the synthesis of not only commodity chemicals but also fine chemicals, taking advantages of chemo-, regio- and enantioselective properties.  The authors will focus upon the treatment of carbacyclic substrates under lipase-catalyzed hydrolysis and transesterification reaction conditions, towards the exploitation of expeditious routes to enantiomerically pure forms of dehydroxymethylepoxyquinomicin (DHMEQ), shikimic and epishikimic acids, and intermediates for oseltamivir.  We especially emphasize the elaboration on “substrate molecular technology”, the importance of the search for the optimized structure and synthetic routes of substrates, which would be maximally advantageous for both selectivity of enzyme-catalyzed reaction, and the total efficiency to target molecules.  Advanced results based on recent examples cited below will be introduced: 1) “Chemoenzymatic synthesis of (2S,3S,4S)-form, the physiologically active stereoisomer of dehydroxymethylepoxyquinomycin (DHMEQ), a potent inhibitor on NF-kB; Tetrahedron, 66, 7083-7087 (2010); 2) Chemoenzymatic synthesis of (2R,3R,4R)-dehydroxymethylepoxyquinomicin (DHMEQ), a new activator of antioxidant transcription factor Nrf2; Org. Biomol. Chem., 9, 4635-4641 (2011); 3) Lipase-catalyzed enantio- and regioselective transformation of 3-epi-shikimic acid derivatives as the key step for the entry of polyoxygenated carbacycles; J. Mol. Catal. B: Enz., 67, 78-84 (2010).