ORGN 910 |
| Guanacastepene A 1 was isolated in 2000 by Clardy and showed excellent antibiotic activity against both MRSA and VREF. The key step in our approach involves a photochemically induced ring expansion/contraction reaction to form the hydroazulene core 2 of the natural product. The relative ease of formation of six membered rings allows for an efficient synthesis of the desired hydronaphthalene precursor 3, which yields the hydroazulene core in a single transformation. The feasibility of the key step has been successfully demonstrated in a racemic synthesis. Work is currently underway on the asymmetric synthesis inserting the isopropyl group in both high yield and enantioselectivity. A diastereoselective nitrile reduction yields the aldehyde 9, allowing for an organolithium cyclisation. An intramolecular Aldol cyclisation yields the hydronaphthalene 10 as a single enantiomer.
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Total Synthesis of Complex Molecules
1:00 PM-5:00 PM, Thursday, 14 September 2006 Moscone Center -- Room 134, Oral
Division of Organic Chemistry |
