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

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 IC50 values of 30 and 150 μM, respectively.