Studies toward the total synthesis of haouamine A

ORGN 34

Nicole D. Smith, smithn@uchicago.edu1, Joji Hayashida1, and Viresh H. Rawal, vrawal@uchicago.edu2. (1) Department of Chemistry, The University of Chicago, 5735 S. Ellis Ave., Chicago, IL 60637, (2) Department of Chemistry, University of Chicago, 5735 South Ellis Avenue, Chicago, IL 60637
Haouamine A (1) and B (2), recently isolated from the ascidian Aplidium haouarianum, are novel metabolites belonging to an unprecedented class of alkaloids. These natural products are characterized by an indeno-tetrahydropyridine moiety comprising the left half, and the strained atropisomeric 3-aza-[7]-paracyclophane moiety on the right half. Haouamine A (1) exhibited selective cytotoxicity for the human colon carcinoma HT-29 cell line (IC50 = 0.1 µg/mL), whereas haouamine B (2), with only an additional hydroxyl group, exhibited selective yet modest cytotoxicity against the mice endothelial MS-1 cell line (IC50 = 5 µg/mL). The interesting biological activity combined with the unique, strained polycyclic skeleton make the houamines attractive targets for chemical synthesis. We disclose our progress toward the total synthesis of haouamine A, which has resulted in the rapid construction of the indeno-tetrahydropyridine portion of the natural product.

 

Total Synthesis of Complex Molecules
8:00 AM-12:00 PM, Sunday, 28 August 2005 Washington DC Convention Center -- 202B, Oral

Division of Organic Chemistry

The 230th ACS National Meeting, in Washington, DC, Aug 28-Sept 1, 2005