Institut de Chimie Moléculaire et des Matériaux d'Orsay

Laboratoire de Synthèse Organique et Méthodologie - LSOM

Synthesis of made up biologically active bearing a silicon atom in their structure

The organosiliciés compounds are the subject of studies, increasingly frequent, their biological properties. For example, the diméthylsilaproline Ia makes it possible to build peptides presenting a biological breakdown much slower compared with the analogues having the amino acid carbonaceous relative, the proline Ib. the silanols IIa and IIIa commercial analogues respectively of the hexahydrodifénidol IIb and the p-fluorohexahydrodifénidol IIIb are, like the latter, of the selective antagonists of receivers muscarinic. They are used to identify and characterize the sub-types of the receivers muscarinic in insulated cells or fabrics. New odorous compounds were obtained by sila-substitution of a carbon atom of a known odorous compound. The comparison of made up IVa and IVb on the one hand and the compounds Goes and Vb on the other hand shows that similar or different fragrances are thus obtained.

In our group, we developed methods to prepare optically active compounds 1 presenting an atom of silicon stereogene (enzymatic reactions), silacycloalcanes 2 (cyclizations ridicalizing) and derivatives of silaisoquinoléinones 3 and silaisochromanones 4 (intramolecular reactions of Diels-Alder). For this last family of compounds, the diastereoselectivity can be controlled by the nature of substituent R.

More recently, we were interested in the compounds bicylic presenting an atom of silicon at the junction of the cycles for which there exists little of methods of synthesis brought back in the literature. The siladécaline 5, silabicycloalcadienes 6 and the silabicyclodécénones 7 were obtained respectively by ridicalizing cyclizations in cascade, reactions of métathèse in cascade or by ène-reaction.

These compounds represent models of cycles A and B or C and D of 10 - and 13-silastéroïdes such as the 10-silatestostérone 8 or the 13-silaœstradiol 9 of which we study the synthesis. Such silastéroïdes could present the pharmacokinetic ones and pharmacodynamics notably different from those of the carbonaceous analogues.

The profadol 10b, the picénadol 11b and the décahydroisoquinoléines 12b are compounds having activities close to morphine. The sila-substitution of quaternary carbon should lead to new compounds 10a, 11a and 12a having a priori close activities but with potentially interesting characteristics. In particular, of the modifications of the ways of metabolisation could allow to avoid nondesired side effects. Biological tests will be carried out to check these assumptions.

Our work thus consists in making the synthesis of sila-compounds whose carbonaceous equivalents present interesting properties, with an aim of modifying them. This work supposes the examination of the particular chemistry of silicon by the development of new reactions.