General synthesis of unnatural 4-, 5-, 6-, and 7-bromo-d-tryptophans by means of a regioselective indole alkylation

Abstract

A general two-step approach to enantiopure bromotryptophans from unprotected bromoindoles has been developed. Indole nucleophiles prepared with MeMgCl in the presence of CuCl reacted with cyclic sulfamidates derived from enantiopure d-serine to form 4-, 5-, 6-, or 7-bromo-d-tryptophan and some other halogenated tryptophans in moderate yields but with complete regioselectivity. The bromotryptophan derivatives were deprotected using mild conditions.