Stereoselective and efficient strategy to synthesize the furanic steroid derivatives

ORGN 752

Siham Farhane, siham.f@gmail.com and Donald Poirier, donald.poirier@crchul.ulaval.ca. Department of Medicinal Chemistry, Oncology and Molecular Endocrinology Research, Laval University, 2705 Blvd Laurier,T4-44, Quebec City, QC G1V 4G2, Canada
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.

 

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
8:00 PM-10:00 PM, Monday, August 17, 2009 Walter E. Washington Convention Center -- Hall D, Sci-Mix

Division of Organic Chemistry

The 238th ACS National Meeting, Washington, DC, August 16-20, 2009