Total Synthesis of Amycolamicin

Abstract

AbstractAmycolamicin (also called kibdelomycin) produced by two species of soil actinomycetes is a potent antibiotic against a broad range of drug-resistant bacteria with a novel binding mode to bacterial type II DNA topoisomerases and with no cross-resistance to existing antibacterial agents. The unique hybrid molecular architecture of amycolamicin attracted interest of many synthetic organic chemists and three total syntheses have been reported so far. In this chapter, we describe our total synthesis of amycolamicin in detail, which features a nucleophilic addition of a vinyllithiun reagent to an α-siloxy-β-alkoxy ketone to afford a tertiary alcohol as a single diastereomer, a highly diastereoselective intramolecular Diels–Alder reaction of a tetraenal with an unprotected hydroxy group to construct a trans-decalin unit incorporated in amycolamicin, an exclusively stereoconvergent N-acylation of an anomeric N-glycoside mixture bearing a cis-fused bicyclic carbonate system, and the exploitation of the cyclic carbonate as a vicinal diol protecting group and also as a masked β-hydroxy carbamate structure. Additionally, two other total syntheses accomplished by the Li and Baran groups as well as syntheses of partial structures of amycolamicin hitherto reported are also outlined in brief.