Inostamycin A has been isolated from the culture broth of a microorganism pertaining to the genus Streptomyces sp. MH816-AF15.1 In the isolation process, inostamycins B and C have also been found together. Their structures were assigned by NMR spectroscopy and later inostamycin A was confirmed by X-ray crystallography of its sodium salt. While inostamycin A has ethyl group at C2, inostamycin B is one-carbon less homolog with methyl substituent instead of the ethyl and inostamycin C corresponds to decarboxylated inostamycin A. Inosamycin A sodium salt is folded around the sodium ion coordinated with its two carboxyl oxygens, two hydroxyl oxygens at C9 and C17, carbonyl oxygen at C11, and ether oxygen between C13 and C16. The folding conformation is believed to be responsible for its various potent physiological properties as an ionophoric polyether antibiotic. Inostamycin A displays inhibitory activity against phosphatidyl inositol turnover and inositol transferase to prevent cell proliferation and transformation, antibacterial activity against Gram-positive bacteria, anti-HIV activity, and reversing effect on multidrug resistance in cancer cells. It also potentiates paclitaxel cytotoxicity, and induces arrest of cell growth at G1 and apoptosis in human small cell lung carcinoma Ms-1 cells.2 Intrigued by its structural complexity and promising biological activities, we have been engaged in synthetic studies on inostamycin A. In this seminar, we present the first total synthesis of the natural product.
1. M. Imoto, K. Umezawa, Y. Takahashi, H. Naganawa, Y. Iitaka, H. Nakamura, Y. Koizumi, Y. Sasaki, M. Hamada, T. Sawa, T. Takeuchi, J. Nat. Prod. 1990, 53, 8252.
2. M. Kawatani, M. Uchi, S. Simizu, H. Osada, M. Imoto, Exp. Cell Res. 2003, 286, 57.