Derivatives of benzo-1,4-thiazine-3-carboxylic acid and the corresponding amino acid conjugates

Abstract

Herein, we present the synthesis and utilization of derivatives of 4H-benzo[b][1,4]thiazine-3-carboxylic acid. These benzothiazine compounds were assembled via the coupling of aminothiols and bromopyruvates. Oxidative dimerization of these starting materials was also observed and the corresponding benzothiazine dimers were isolated. Moreover, the coupling of benzothiazines with amino acids was realized. In doing so, an enantioselective synthesis of the nonproteinogenic amino acid 2-amino-3-propylhexanoic acid was accomplished.

The Multifaceted Opportunities Provided by the Pheomelanin-Inspired 1,4-Benzothiazine Chromophore: A Still-Undervalued Issue

“…2-Aminothiophenol undoubtedly represents one of the main synthetic precursors of 1,4-benzothiazines, as recently reviewed in several papers, and α-bromo carbonyl compounds, such as bromopyruvates or phenacyl bromides, as well as dicarbonyl compounds, are commonly employed as the electrophilic counterpart [30][31][32]. Current research is, therefore, particularly devoted to the development of green and biocompatible reaction conditions for the implementation of synthetic strategies based on the use of this compound, as demonstrated by the numerous papers that have fleshed out, in the last three years, the very poor relevant scenario (only three examples) dating back seven years [4].…”