Stereoselective and efficient strategy to synthesize the furanic steroid derivatives

ORGN 752

Siham Farhane, and Donald Poirier, 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

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