Use of Dihydroxyacetone Phosphate Dependent Aldolases in the Synthesis of Deoxyazasugars

Article abstract of DOI:10.1021/jo00022a013

The use of fructose-1,6-diphosphate (FDP), fuculose-1-phosphate (Fuc-1-P) and rhamnulose-1-phosphate (Rham-1-P) aldolases in organic synthesis is described.Fuc-1-P, Rham-1-P, and their phosphate-free species have been prepared and characterized.Both Fuc-1-P and Rham-1-P aldolases accept 3-azido-2-hydroxypropanal as a substrate to form L-ω-azidoketose phosphates, which upon dephosphorylation and hydrogenolysis on Pd/C, gave 1-deoxyazasugars structurally related to D-galactose and L-mannose.Hydrogenolysis of the enzyme products azidoketose 1-phosphates, however, gave 1,6-dideoxyazasugars structurally related to 6-deoxygalactose and L-rhamnose.Explanations for the stereoselectivity in the hydrogenolysis reactions were provided.Similarly, FDP aldolase catalyzed the aldol condensation reaction with 2-azido-3-hydroxypropanal to afford a new synthesis of 2(R),5(S)-bis(hydroxymethyl)-3(R),4(R)-dihydroxypyrrolidine, a potent inhibitor of a number of glycosidases.A new empirical formula is developed to relate the inhibition constants and inhibitor binding for α- and β-glucosidases.