|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.
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