Total synthesis of a dibromotyrosine alkaloid inhibitor of mycothiol S-conjugate amidase

Two complementary synthetic sequences are described for the first total synthesis of a dibromotyrosine alkaloid (1) reported to inhibit a critical mycobacterial enzyme, mycothiol S-conjugate amidase. The O-benzyloxime of 4-hydroxyphenylpyruvic acid was dibrominated and successively linked to a 3-aminopropyl chain, then to a 4-aminobutylguanidine unit, followed by selective deprotections to yield alkaloid 1. In an improved variant, the O-tetrahydropyranyloxime 12 was condensed with 4-aminobutylguanidine then dibrominated to phenol 14, which upon Mitsunobu coupling to a 3-aminopropyl segment and deprotection produced the target 1.