ORGN 752 |
| We have developed an efficient strategy for the preparation of chiral furanic-steroid derivatives. Ring-closing metathesis and catalytic hydrogenation are the key steps in this synthesis. The synthetic strategy was first illustrated by the chiral synthesis of the furanic-estrane derivative 1 in seven steps starting from estrone and 2-methylene-propane-1,3-diol. This compound initially targeted as a potential inhibitor of 17β-hydroxysteroid dehydrogenase type 1 by a docking experiment was found to inhibit the enzyme. When using two different protective groups, the synthetic strategy allows us to introduce a molecular diversity at both C3 and C3'-positions, which are two locations playing a crucial role in maximizing interactions between steroidal derivatives and targeted enzymes such as 17β-HSD1. The scope of this new strategy was extended to androstane nucleus and could also be used for the preparation of additional steroidal or non-steroidal furanic derivatives, thus extending our methodology to other families of therapeutic agents.
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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
Sci-Mix
Division of Organic Chemistry |
