Total Synthesis of TAN-1057 A/B, a New Dipeptide Antibiotic fromFlexibacter sp. PK-74

Abstract

TAN-1057 (1a, b) − a new natural dipeptide antibiotic active against methicillin resistant strains of Staphylococcus aureus − was synthesized starting from Nα, Nδ, Nω-tri-Z-L-arginine 20b via the corresponding diazoketone 21b. This upon photolysis rearranged to the ketene which was trapped by (±)-2,4,5,6-tetrahydro-5-methylamino-2-ureidopyrimidin-4-one (3) to yield the fully protected dipeptide 23 (30%). The latter was deprotected by hydrogenolysis to give the final compound as a mixture of two epimers − TAN-1057A, B − isolated previously from a strain of Flexibacter sp. PK-74. The intermediate 3 was prepared from 3-amino-2-(N-Z-N-methylamino)propionic acid methyl ester hydrochloride (16) and 2-methyl-2-thiopseudobiuret hydroiodide (18) in one step in 35% yield.