ORGN 458 |
| (–)-Haouamine A is a biologically active marine metabolite with an unusual polycyclic structure. It exhibits potent, selective cytotoxic activity against a human colon carcinoma cell line. A racemic total synthesis of (±)-haouamine A has been reported by Baran and Burns. In the present contribution, we describe our efforts toward an enantioselective total synthesis of the natural product. Our retrosynthetic approach involves initially disconnecting the strained paracyclophane ring of (–)-haouamine A along its biaryl C-C bond. The functionalized heterocycle core of our macrocyclization substrate (2) may be obtained via 6-endo-cyclization of an advanced achiral intermediate (1). Tertiary amine 1, in turn, can be assembled in a convergent fashion from four different precursors of approximately equal complexity. Asymmetric induction is accomplished in the course of forming the natural product's distinctive all-carbon quaternary stereocenter. Several strategies for this transformation (1→2) are discussed. Special attention is given to the role of indene oxidation state and alkenyl functionality in determining reaction selectivity.
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Total Synthesis of Complex Molecules
8:00 AM-12:00 PM, Wednesday, April 9, 2008 Morial Convention Center -- Rm. R05, Oral
Division of Organic Chemistry |
