Halogenase-Assisted Biocatalytic Derivatization of Aminothiazoles and Cephalosporin Antibiotics

Abstract

With a view toward the prominence of brominated intermediates in chemical synthesis, we describe here a biocatalytic scheme for the enzymatic bromination of 2-aminothiazoles using a marine macroalgal brominase in reaction conditions that are directly compatible with Suzuki–Miyaura cross-coupling reactions. Enzymatically delivered brominated thiazoles, without intermediary purification, are arylated in high yields. We demonstrate the applicability of the methodology described herein in derivatizing clinically administered cephalosporin antibiotics and prodrugs in an aqueous solvent and mild reaction conditions.