Studies toward the total synthesis of amphidinol 3

ORGN 650

Jacqueline D. Hicks, jdhicks@umich.edu, Department of Chemistry, University of Michigan, 930 N. University, Ann Arbor, MI 48109 and William R. Roush, roush@scripps.edu, Department of Chemistry, Scripps-Florida, 5353 Parkside Drive, RE-2, Jupiter, FL 33458.
Amphidinol 3 (AM3) is a polyketide-derived natural product, produced by the marine dinoflagellate Amphidinium klebsii, which displays anti-fungal activity against Aspergillus niger and hemolytic activity of human erythrocytes. As a result of this interesting biological activity and its complex architecture, AM3 has received considerable attention from the synthetic community. Our approach to AM3 highlights the double-allylboration methodology developed within our laboratory for the synthesis of 1,5-diols. Our general strategy involves cyclization of a 1,5-diol to provide a dihydropyran which can be transformed to the two pyran containing fragments of AM3. We have employed a base-mediated cyclization of a functionalized 1,5-diol to provide a common dihydropyran intermediate, which is then further elaborated to give the stereochemically identical C(31)-C(40) and C(43)-C(52) tetrahydropyrans of AM3. Conversion of this common pyran intermediate to the C(26)-C(42) and C(43)-C(67) fragments and efforts toward the total synthesis of AM3 will be discussed.
 

Total Synthesis of Complex Molecules
8:00 AM-12:00 PM, Wednesday, 13 September 2006 Moscone Center -- Room 132, Oral

Division of Organic Chemistry

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