Diastereo and enantioselective reactions synthesis of heterocyclic building blocks of biological importance

International Conference on Stereochemistry

August 18-19, 2016 Sao Paulo, Brazil

Janine Cossy

ESPCI ParisTech, France

Posters & Accepted Abstracts: Med chem

Abstract :

In biologically active compounds, stereochemistry is of great importance. For example in the case of thalidomide, prescribed for the treatment of morning sickness in pregant women, the (R)- and (S)-enantiomers have not the same bioactivity. One is safe and the other one is teratogenic. Thus, it is of importance to develop methods that are highly steroselective to produce diastereomers and enantiomers. In this context, we have explored the construction of heterocycles such as substituted piperidines, -C- and -glycosides, using reactions catalyzed by transition metals or thermal reactions. Enantioselective ring expansion of prolinols were tuned up to produce a diversity of C3-substituted piperidines. Excellent enantioselectivity were obtained when prolinols were activated by trifluoroacetic anhydre (TFAA), (diethylamino)sulfur trifluoride (DAST). We have demostrated that an aziridium intermediate was involved in the enantioselective ring expansion of substituted prolinols leading to optically active substituted piperidines. As -Cand -C-glycosides have interesting biological activities, the development of efficient and stereoselective methods to access -C- and -C-glycosides are of importance. For our part, we were able to synthesize -C-glycosides from hydroxy-allylic alcohols when treated with a Lewis acid and we were able to synthesize -C-glycosides from bromo-C-glycosides when these latter were treated with Grignard reagents in the presence of transition metal catalysts. On the other hand, we were able to access functionalized heterocycles containing oxygen with excellent diastereoselectivity from substituted cyclopropenes when treated with transition metals. The obtained compounds can be useful synthons that can be used to synthesized bioactive products. The scope and limitations of the developed methods, to access heterocycles containing nitrogen and oxygen, will be presented and the obtained stereoselectivities will be rationalized.

Biography :

Email: janine.cossy@espci.fr