Total Synthesis of Antibiotic BE-43472B

Abstract

Antitumor antibiotic BE-43472B was first isolated in 1996 by Banyu from Streptomyces sp. A43472, and recently rediscovered by Rowley from metabolites of marine microorganism synbiotic to a Caribbean ascidian (Ecteinascidia turbinata). In addition to the antitumor activity, the latter study uncovered significant bactericidal activity against drug-resistant pathogens, such as MSSA, MRSA, and VRE. The basic structure is composed of two non-identical anthraquinone moieties connected by a highly hindered carbon–carbon bond. Also notable is the stereochemical complexity associated with the five contiguous stereogenic centers. The important biological activities as well as the uniquely complex molecular architecture have stimulated considerable synthetic interests, and Nicolaou reported the first total synthesis.

In this talk, we will present the second total synthesis of BE-43472B, featuring: 1) use of isoxazole as a 1,3-diketone surrogate, 2) the isoxazole-directed pinacol 1,2-shift for connecting two anthraquinone precursors at the angular position, and 3) perfect control of five contiguous stereogenic centers. The synthetic route is flexible enough to allow the synthesis of the chiral, non-racemic ones as well as the various congeners with potential biological activities.