Regio- and Stereoselective Synthesis of Deuterium-Labeled Glutamic Acids via a Tetramic Acid Derivative

Abstract

In this study, stereoselective deuterium labeling of the side chain of glutamic acid was investigated. Treatment of tetramic acid derived from d-serine and Meldrum’s acid with sodium borohydride-d4 and/or acetic acid-d1, followed by formal dehydration, enabled the construction of a 3,4-didehydropyroglutaminol framework bearing deuterium labels at the olefin position. Further catalytic hydrogenation or deuteration of olefins ultimately enabled the synthesis of seven isotopomers of glutamic acid regio- and stereoselectively deuterated at the β- and γ-positions.