Complete Stereochemistry and Preliminary Structure–Activity Relationship of Rakicidin A, a Hypoxia-Selective Cytotoxin from <i>Micromonospora</i> sp.

The complete stereochemistry of rakicidin A, a hypoxia-selective cytotoxin produced by <i>Micromonospora</i> sp., was unambiguously established by extensive chemical degradation and derivatization studies. During the PGME derivatization-based configurational analysis of 3-hydroxy-2,4,16-trimethylheptadecanoic acid, an irregular Δδ distribution was observed, which necessitated further acylation of the 3-hydroxy group to resolve the inconsistency. A hydrogenated derivative of rakicidin A, its ring-opened product, and two congeners with different alkyl chain lengths were tested for hypoxia-selective cytotoxicity. The results indicated that both the conjugated diene unit and appropriate chain length are essential for the unique activity of rakicidin A