The synthesis, configuration, and conformation of cis‐ and trans‐3‐amino‐3,4‐dihydro‐1‐hydroxy‐4‐methylcarbostyrils and other configurationally related compounds

Abstract

AbstractThe cis‐ and trans‐3‐amino‐3,4‐dihydro‐1‐hydroxy‐4‐methylcarbostyrils (Ia and Ib) were synthesized by catalytic hydrogenation of erythro‐ and threo‐α‐amino‐β‐(o‐nitrophenyl)butyric acid hydrochlorides, IIIa and IIIb, respectively, under acidic conditions. The free bases of IIIa and IIIb were catalytically hydrogenated under neutral conditions to yield the erythro‐ and threo‐α‐amino‐β‐(o‐aminophenyl)butyric acids (VIa and VIb), which were converted by acidification to their corresponding lactams, cis‐ and trans‐3‐amino‐3,4‐dihydro‐4‐methylcarbostyrils, IIa and IIb. The erythro and threo isomers of α‐amino‐β‐(o‐nitrophenyl)‐butyric acid were prepared and separated by liquid chromatography via a diastereomeric mixture of (V) of methyl α‐acetamido‐β‐(o‐nitrophenyl)butyrates. The configurations and conformational assignments of the cyclic hydroxamic acids Ia and Ib were first established by analysis of the proton nmr spectra. In turn, the configurations of the o‐nitroaromatic amino acids IIIa and IIIb were assigned as well as the other structurally related compounds (VIa, VIb, IIa and IIb) derived therefrom.