Total Synthesis of the Antibiotic BE-43472B

摘要

The antitumor antibiotic BE-43472B (1) was first isolated in 1996 by researchers at Banyu from Streptomyces sp. A43472 (Figure 1), and recently rediscovered by Rowley and co- workers from a Caribbean ascidian (Ecteinascidia turbi-nata) In addition to antitumor activity, the latter study uncovered a significant bactericidal activity of 1 against drag-resistant pathogens, such as MSSA, MRSA, and VRE. The basic structure of 1 is composed of two nonidentical anthraquinone moieties connected by a highly hindered carbon-carbon bond. Also notable is the stereochemical complexity associated with the five contiguous stereogenic centers. Important biological activities as well as the uniquely complex molecular architecture of 1 have stimulated considerable synthetic interests and Nicolaou and co-workers reported the first total synthesis of 1, which was accomplished in 21 steps in 1.0% yield by exploiting a cascade sequence including a Diels-Alder reaction.