Two complete syntheses of (S)-aspartate semi-aldehyde and demonstration that Δ²-tetrahydroisophthalic acid is a non-competitive inhibitor of dihydrodipicolinate synthase

Abstract

We report, in full, two 3-step syntheses of (S)-aspartate semi-aldehyde, an important synthetic and biosynthetic precursor, from diprotected aspartic acid. The first synthesis proceeds via a thioester, the second via a Weinreb amide. Each route yields pure (S)-aspartate semi-aldehyde in excellent yield. The utility of (S)-aspartate semi-aldehyde prepared in this manner was demonstrated with an inhibition study of dihydrodipicolinate synthase, wherein Δ2- tetrahydroisophthalic acid is shown to be a non-competitive inhibitor with respect to both substrates.