CATALYTIC CHEMO-ENZYMATIC ASYMMETRIC SYNTHESIS OF CARBOHYDRATES

摘要

A stereoselective synthesis of carbohydrates employs two key stereoselective steps, viz. an osmium-catalyzed asymmetric dihydroxylation (AD) of an alkene to form an aldol intermediate and an aldolase-catalyzed aldol addition reaction wherein the aldol intermediate is elongated by the addition of a ketone. Moreover, ketoses having four new stereocenters can be synthesized without the use of chiral starting materials. The stereoselectivity of the asymmetric dihydroxylation (AD) reaction is determined by the cis or trans (Z or E) stereoisomeric configuration of the alkene and by the choice of AD-mix, i.e., an AD-mix-α or AD-mix-β. The stereoselectivity of the aldolase-catalyzed addition reaction is determined by the choice of aldolase and by the stereochemistry of the aldol intermediate. Four aldolases with broad substrate specificity are sufficient to produce all possible enantiomeric combinations of the two hydroxymethylene stereocenters formed during the aldol addition reaction. Accordingly, a synthetic scheme combining an osmium-catalyzed asymmetric dihydroxylation (AD) reaction and an aldolase-catalyzed aldol addition reaction enables direct access to a wide range of carbohydrate derivatives containing up to four new hydroxymethylene stereocenters.