Efficient stereoselective synthesis of (2S,3S,4S)-3,4-dihydroxyglutamic acid

(2S,3S,4S)-3,4-Dihydroxyglutamic acid (DHGA), a biologically active α,β-dihydroxy-γ-amino acid, was efficiently synthesized from a readily available D-serine derivative in 30% overall yield over 11 steps. The key stereoselective OsO4-catalyzed dihydroxylation reaction controlled by an N-diphenylmethylene group on the amino group of γ-amino-α,β-unsaturated (Z)-ester successfully introduced the diol moiety of the intermediate 5a in 86% with more than 10: 1 diastereomeric ration. Then it was in turn successfully converted to the desired target compound, (2S,3S,4S)-3,4-DHGA, via simple oxidation and hydrolysis in a highly stereoselective manner and a higher yield than the previous syntheses. This result strongly supports that our synthetic methodology of stereoselective OsO₄-catalyzed dihydroxylation should be useful in stereoselctive synthesis of various bioactive compounds with an amino diol moiety.