ORGN 430 |
| Tedanolide, an architecturally coplex marine macrolide, isolated from Tedania ignis has displayed potent antitumor activity. Low natural abundance coupled with potent biological activity has prompted us to pursue the synthesis of this macrolide. Our retro-synthetic strategy for Tedanolide (1) involves the disconnections leading to three fragments namely 3 (C18-C23), 5 (C8-C17) and 6 (C1-C9) as shown in figure 1. Fragments 5 and 6 were designed to be connected by olefin cross-metathesis followed by Yamaguchi macro-lactonization. Subsequently fragment 3 is planned to be introduced through its vinyl anion. The stereo-selective synthesis of fragments 5 and 6 was successfully completed and the results of the same were already presented at ACS 230th & 231st national mettings respectively. However subsequent efforts to assemble these fragments by olefin cross-metatheis are failed. Hence we slightly modified the plan of assembling of these fragments. Accordingly fragments 5 and 6 were first connected by Yamaguchi esterification and subsequent ring closing metathesis between the two terminal olefins resulted in macrolide core. Detailed synthetic strategy and the results of stereo-selective synthesis of macrolide core of tedanolide will be discussed.
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Process R&D and Practical Syntheses of Medicinal Agents
1:00 PM-4:40 PM, Tuesday, 12 September 2006 Moscone Center -- Room 132, Oral
Division of Organic Chemistry |
