Tartrate dehydrogenase reductive decarboxylation: stereochemical generation of diastereotopically deuterated hydroxymethylenes.
Tartrate dehydrogenase catalyzes the reductive decarboxylation of meso-tartrate to glycerate. Concomitant with the ketonization of the intermediate enolate the C3 hydroxymethylene of glycerate necessarily acquires a proton from solvent. In D2O, the proton is shown to be added stereospecifically to form (2R,3R)-[3-2H]glycerate. The 1H-NMR assignments of the diastereotopic C3 protons of glycerate were confirmed by the enzymatic conversion of [1R-2H]fructose-6-phosphate to (2R,3R)-[3-2H]glycerate. The decarboxylation-protonation occurs with retention of configuration, implying that the general acid is positioned on the same face of the intermediate as the departing carboxylate. The stereochemically pure (2R,3R)-[3-2H]glycerate is readily synthesized and serves as a chiral hydroxymethylene synthon as demonstrated by the synthesis of (2S,3R)-[3-2H]serine.
Ruszczycky
Mark W
MW
Department of Biochemistry, Case Western Reserve University, Cleveland, OH 44106-4935, USA.
Anderson
Vernon E
VE
D000429:Alcohol Oxidoreductases / Q000737:chemistry*; D002384:Catalysis; D003653:Decarboxylation; D003903:Deuterium / Q000737:chemistry; D004789:Enzyme Activation; D005988:Glyceric Acids / Q000737:chemistry*; D006838:Hydrocarbons; D008697:Methane / Q000031:analogs & derivatives* / Q000737:chemistry*; D008968:Molecular Conformation; D010084:Oxidation-Reduction; D012694:Serine / Q000737:chemistry; D013237:Stereoisomerism; D013644:Tartrates / Q000737:chemistry*
D005988:Glyceric Acids; D006838:Hydrocarbons; D013644:Tartrates; C030011:carbene; D012694:Serine; D003903:Deuterium; D000429:Alcohol Oxidoreductases; C038481:tartrate dehydrogenase; D008697:Methane