ORGN 784 |
| Ever since the first isolation and structural elucidation of macrosphelides in 1990s, these marine polyketides have attracted much interest from biologists because of their potent tumor-metastasis-suppressant and immunomodulating activities. In addition, their unique macrocyclic tri-ester skeleton with five stereogenic centers has also attracted interest from synthetic chemists. In this connection, we have achieved highly efficient and convergent syntheses of macrosphelide A and B. The key feature of the syntheses includes efficient preparation of γ-keto-α,β-unsaturated acid fragment via a direct addition of trans-vinylogous ester anion equivalent to the readily available Weinreb amide. In particular, the facile construction of the 16-membered marcrolide core of the macrosphelide B was achieved by an intramolecular nitrile oxide-olefin cycloaddition (INOC), which provided excellent regio and streoselectivity. We have also accomplished the first total syntheses of macrosphelides J and K from ethyl (S)-(-)-lactate in 15 steps using chiral sultam auxiliary. Thus, we extended our work to elucidate their structures, particularly the stereochemistries of five stereocenters. |
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Heterocycles and Aromatics, Asymmetric Reactions and Syntheses and Total Synthesis of Complex Molecules
7:00 PM-9:00 PM, Wednesday, August 19, 2009 Walter E. Washington Convention Center -- Ballroom C, Poster
Division of Organic Chemistry |