Synthesis of 2‐oxo and 6‐hydroxylated benzimidazole analogs of DOPA as potential norepinephrine antagonists

Abstract

The synthesis of benzimidazolone analogs of DOPA and α‐methyl‐DOPA and of the benzimidazole and benzimidazolone analogs of 6‐hydroxy‐DOPA is reported. These compounds showed a moderate amount of dopamine β‐hydroxylase and tyrosine hydroxylase inhibitory activity but did not significantly alter tissue catacholamine levels.

Catalytic Asymmetric Syntheses of Tyrosine Surrogates

“…Diamine 28 was converted into amino acid esters 8 − 10 as shown in Scheme . Benzotriazole amino ester 8 was obtained in 80% yield and 99.6% ee (two steps, from 27 ) by the reaction of 28 (X = OAc) with NaNO 2 . The reaction of diamine 28 (X = Cl) and carbonyl diimidazole afforded benzoimidazolone amino ester 9 in 50% yield (2 steps, from 27 ) .…”

“…The ee of amino ester 9 was not determined. Finally, 2-methylbenzimidazole amino ester 10 was obtained in 81% yield and 97.6% ee (2 steps, from 27 ) by heating diamine 28 (X = OAc) in AcOH at reflux for 4 h …”

“…A seven step racemic synthesis of free oxoindole amino acid 7 (without CBz protection) was reported in 1979 . Racemic amino acids 8 − 10 have been synthesized by the reaction of substituted benzyl bromides with sodioethylacetamidomalonate or its equivalent, and were used as DOPA and dopamine analogues to study their effects on dopamine β-hydroxylase and tyrosinase . They have also been prepared in racemic form by nitration of 4-aminophenylalanine to study their potential as inhibitors of norepinephrine biosynthesis .…”