CaprazamycinA has significant antibacterial activity against Mycobacterium tuberculosis (TB). The first total synthesis is herein reported and features a)the scalable preparation of the syn--hydroxy amino acid with a thiourea-catalyzed diastereoselective aldol reaction, b)construction of a diazepanone with an unstable fatty-acid side chain, and c)global deprotection with hydrogenation. This report provides a route for the synthesis of related liponucleoside antibiotics with fatty-acid side chains.