Use of a recombinant bacterial fructose-1,6-diphosphate aldolase in aldol reactions: Preparative syntheses of 1-deoxynojirimycin, 1-deoxymannojirimycin, 1,4-dideoxy-1,4-imuno-D-arabinitol, and fagomine

Article abstract of DOI:10.1021/ja00193a025

A combined enzymatic aldol condensation and catalytic intramolecular reductive amination has been used in the high-yield asymmetric synthesis of polyhydroxylated alkaloids including 1-deoxynojirimycin, 1-deoxymannojirimycin, 1,4-dideoxy-1,4-imino-D-arabinitol, and fagomine. The Escherichia coli Zn²⁺-containing fructose-1,6-diphosphate aldolase overexpressed in E. coli was used for the syntheses. The enzyme in aqueous solution containing 0.3 mM ZnCl₂ has excellent stability with a half-life of 60 days, compared to 2 days for the enzyme from rabbit muscle. The reactions were carried out under mild conditions without protection of functional groups. Either dihydroxyacetone phosphate or a mixture of dihydroxyacetone and inorganic arsenate can be used as donor in the aldol reactions. The aldol acceptors (R)- and (S)-3-azido-2-hydroxypropanal were prepared via lipase-catalyzed resolution of the racemic acetal precursor.