Synthesis of a bromotyrosine-derived natural product inhibitor of mycothiol- S -conjugate amidase

Bioorganic & Medicinal Chemistry Letters
2004.0

Abstract

Recently we described the structures of two new bromotyrosine-derived alkaloids that inhibit the detoxification enzyme mycothiol-S-conjugate amidase (MCA) from Mycobacterium tuberculosis. Here we describe a concise total synthesis of bromotyrosine oxime 1. The six-step synthesis of 1 utilized a trifluoromethyloxazole intermediate, whose hydrolysis product underwent alkylation and coupling to agmatine to give the inhibitor in ∼40% overall yield. Oxime 1 inhibited MCA and its homolog AcGI deacetylase with IC 50 values of 30 and 150μM, respectively. © 2004 Elsevier Ltd. All rights reserved.

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