Enzymes in organic synthesis

Vita.The synthetic utilities of enzymes as catalysts for asymmetric synthesis have been explored in several aspects. Fructose-1,6-diphosphate aldolase from rabbit muscle and E. coli, rhamnulose-1-phosphate aldolase and fuculose-1-phosphate aldolase have been used in the syntheses of common sugars and other sugar-related substances. Furthermore, a combined aldolase reaction and catalytic reductive amination has been developed in the asymmetric synthesis of azasugars--a class of molecules as glycosidase inhibitors. Azidoketose-1-phosphates, the aldolase products, upon de-phosphorylation and hydrogenolysis to give 1-deoxyaza-sugars. However, direct hydrogenolysis of azidoketose-1-phosphates gives dideoxyazasugars. In the reductive amination, hydrogen always approaches the face opposite to any axial substituent, or approaches the imine intermediate in a facial selective manner to avoid torsional strain. If the factors are in contrast, the former overrides the latter. Of the azasugars synthesized, the most interesting are the five-membered-ring azasugars. These compounds possess a half-chair-like envelope conformation and a positive charge to mimic the transition state of glycosidic cleavage and therefore act as potent inhibitors of several glycosidases. FDP aldolase was also used to synthesized nucleoside analogues. This enzymatic strategy provides an efficient way to incorporate different biologically interesting bases into a sugar moiety and generates different C-nucleosides. The lipase resolution of 2-acetoxy-3-tosylate-propane, 2-acetoxy-1-(benzyloxy)-3-chloropropane, and various 3-substitued-2-acetoxy propanal diethyl acetals were examined. These compounds are easily converted to the corresponding epoxides. This provides a chemoenzymatic access to optically active 1,2-epoxides. Procedures for the resolution of several cyanohydrins via lipase-catalyzed irreversible transesterification were developed, and the syntheses of ethyl-(R)-2-hydroxy-4-phenylbutyrate and (S)-propranolol from enantiomerically pure cyanohydrins are demonstrated..