ORGN 747 |
| Lepadins are an interesting family of natural products containing a cis-decahydroquinoline structure characterized by five stereogenic centres. Lepadin B, isolated in 1995 by Kubanek and co-workers, has been shown to exhibit significant cytotoxic activity against several human cancer cell lines. Since its isolation, three research groups have reported asymmetric total syntheses of this alkaloid. As a new and shorter approach to Lepadin B, we envisaged a ROM-RCM sequence to access the poly-substituted cis-hydroquinoline core. Accordingly, we hypothesized that the diene 2 could serve as a ROM-RCM precursor to produce the cis-hydroquinoline 3. The synthesis of 2 was achieved by applying the highly diastereoselective Diels-Alder strategy recently published by our group. This strategy starts with the dihydropyridine 1, of which we reported a one-step synthesis from pyridine in 77 % yield and >95/5 dr. In this paper, we present the details of the asymmetric synthesis of 2, validate the efficacy of the ROM-RCM approach to the cis-hydroquinoline structure and discuss our progress toward the total synthesis of Lepadin B.
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Total Synthesis, Materials, Molecular Recognition, Process R&D, and Physical Organic Chemistry
8:00 PM-10:00 PM, Wednesday, 13 September 2006 Moscone Center -- Hall D, Poster
Division of Organic Chemistry |
