Synthesis of Non-proteinogenic Amino-Acid Methyl Esters with Acid-Sensitive Side Chains from a Chiral Glycine Derivative

Abstract

A superior chiral glycine derivative 1 (tert-butyl 2-(tert-butyl)-4-methoxy-2,5-dihydro-1,3-imidazole-1-carboxylate, BDI) for the synthesis of acid-sensitive and highly hindered α-amino-acid methyl esters is readily available by resolution methods. The heterocycle 1 is alkylated once and twice in the 5-position with very high diastereoselectivity, and the resulting products (2, 3) are hydrolyzed under very mild conditions to give methyl esters of the corresponding amino acids (6–10).