Total Synthesis and Structure Revision of the (-)-Maduropeptin Chromophore

摘要

Maduropeptin, a novel member among the family of chromopro-tein antitumor antibiotics, was isolated from the broth filtrate of Actinomadura madurae by scientists at Bristol-Myers Squibb in 1991. The isolated chromophore 1 was composed of a unique nine-membered diyne core and a glycoside side chain (Figure 1). Although 1 is the methanol adduct of a structurally undefined labile chromophore, it showed a DNA cleavage site selectivity similar to that of holoprotein. Presumably, the activation mechanism of 1 is initiated by the formation of the highly strained nine-membered enediyne ring via intramolecular S_N2' substitution of methanol by the macrolactam nitrogen.