Natural Products Synthesis

Rhizopodin (1, Scheme 1) is an architecturally unique polyketide macrolide that was originally isolated from the myxobacterium Myxococcus stipitatus by the groups of Hçfle and Reichenbach. It shows potent antifungal and antiproliferative cytotoxicity against a range of tumor cell lines with IC50 values in the low nanomolar range. [1] On a molecular level, 1 disrupts the cytoskeleton of actin by binding specifically to a few critical sites of G-actin. Actin presents one of the twomajor components of the cytoskeleton in eukaryotic cells, in which it plays a critical role in the determination of cell shape and a variety of cellular processes, including cell motility, division, adhesion, and intracellular transportation. Actin-binding agents are becoming increasingly important as molecular probes to understand the organization and unveil the cellular functions of actin, and as potential lead structures for the development of novel chemotherapeutic anticancer agents. Rhizopodin has also been shown to reduce phagocytosis efficiency of yeast cells. While rhizopodin was initially reported to be a planar monomeric structure, its revised structure was reported to be a C2-symmetric dimer, which is distinguished by a 38membered macrolide ring, two conjugated diene systems in combination with two disubstituted oxazole systems, and two side chains, which are terminated by N-vinylformamide moieties. In total, it contains 18 stereogenic centers in the