Combination of Enzymatic Oxidation of Amino Acid and Native Chemical Ligation with Hydroxylamine for Amide Formation toward a One-pot Process

Abstract

The formation of amide bonds is important in many areas of chemistry, and the ligation by condensation of N-hydroxylamine and an α-keto acid has been attracting increasing attention. Porcine kidney d-amino acid oxidase, which catalyzes the oxidative deamination of amino acids to yield α-keto acids, ammonia, and hydrogen peroxide, and native chemical ligation were used to access α-keto acids, and amides were synthesized with N-hydroxylamine. d-Phenylalanine was converted to phenylpyruvic acid obtained by recombinant pig d-amino acid oxidase in high yield (97%). The α-keto acid was ligated with N-benzylhydroxylamine and N-hydroxylphenylalanine in N,N-dimethylformamide, and benzyl-2-phenylacetamide and (2-phenylacetyl)phenylalanine in 82% and 79% yields, respectively. Other amide compounds were also obtained via this synthesis.