ORGN 308 |
| Scott D. Rychnovsky, Leo R. Takaoka, and Alexandre J. Buckmelter. Department of Chemistry, University of California, Irvine, 516 Rowland Hall, Irvine, CA 92697-2025 |
| The spongistatins (altohyrtins) comprise a growing class of marine-derived macrolides that possess complex architecture and display subnanomolar cytotoxicity. The unique CD spiroketal fragment consists of a single anomeric stabilizing interaction (contrathermodynamic) which offers a formidable challenge for direct access. Many approaches have relied on thermodynamic isomerization of the anomeric stereocenter (C23) taking advantage of an internal metal chelate or intramolecular hydrogen bond. Our approach entails the kinetic formation of the natural C23 stereocenter via a novel reductive cyclization process utilizing cyano groups as the penultimate precursor. The reductive decyanation of a cyclic cyanoacetal followed by alkyllithium cyclization represents a potential entry into the direct formation of contrathermodynamic spiroketals. Progress toward the CD–subunit of spongistatin 1 (altohyrtin A) will be described. |
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New Reactions and Methodology
8:00 AM-12:00 PM, Tuesday, September 9, 2003 Sheraton New York -- Royal Ballroom B, Oral
Division of Organic Chemistry |