Synthesis of 3-Hydroxylated Analogues of D-Aspartic Acid β-Hydroxamate

Abstract

The two isomers (2R,3R) and (2R,3S) of 3-hydroxy-D-aspartic acid β-hydroxamate were synthesised from diethyl tartrates via the corresponding diethyl 3-hydroxyaspartates.

Notes

LAH (L isomer of DAH) showed comparable activities to those of DAH but was more toxic. Thus, D configuration is maintained for analogues.

A sufficient amount of NaOH is necessary to complete transformation in reasonable time. A side reaction is saponification of diester which appears when NaOH / NH₂OH ratio is too high (a 3/4 ratio is a good compromise). On the other hand, the N-hydroxysuccinimide derivative i was isolated if this ratio is two low. The role of NaOH and the mechanism of the transformations of diesters into monohydroxamates are under study.