Progress toward the total synthesis of Sclerophytin A

ORGN 163

John M. Hutchison, jmh23@uark.edu1, Harriet A. Linsday2, Silvana S. Dormi, sdormi@uark.edu1, Gavin Jones1, and Matthias C. McIntosh1. (1) Department of Chemistry and Biochemistry, University of Arkansas, 205 Science Building, Fayetteville, AR 72701, (2) Department of Chemistry, Eastern Michigan University
Sclerophytin A is eunicellin diterpene cytotoxic against the L1210 leukemia cell line. Our synthetic route employs an Ireland-Claisen rearrangement of a bis-allylic ester to install the C7 stereocenter. The pentadienoic acid product of the rearrangement was prepared in 5 steps from (S)-(+)-carvone and lacks only the C2-C5 carbons. Following a diastereoselective Ag(I)-mediated syn SN2' lactonization of the dienic acid, a novel Cu(I)-mediated anti SN2' addition of an alkoxymethyl nucleophile was used to install the C1-C2 bond. The furan ring was accessed by a base-promoted cyclization of the C9 oxygen. Subsequent installation of the C10 stereocenter was achieved via an allylic diazene rearrangement. Further progress toward the target will be presented.

 

Asymmetric Reactions and Syntheses, Metal-Mediated Reactions, Combinatorial, Parallel, and Solid-Phase Chemistry
8:00 PM-10:00 PM, Sunday, 10 September 2006 Moscone Center -- Hall D, Poster

Division of Organic Chemistry

The 232nd ACS National Meeting, San Francisco, CA, September 10-14, 2006