Synthesis and use of bile acid derived organocatalysts

The central idea of this work was design, synthesis and study of catalytic activity and enantioselectivity of new organocatalysts containing a chiral cavity mimicking the enzymatic pocket of Aldolase I. Following the longstanding interest of our research group in the use of bile acid derivatives in enantioselective processes, attention was addressed to the development of organocatalysts having bile acid structure, where, because of its concave structure, due to the cis junction of the A and B cyclohexanic rings (Figure 3), the cholestanic backbone and the appended substituents should form a chiral cleft that can help the enantioselection. In addition, the presence of free hydroxyl groups can constitute a further advantage by controlling, via hydrogen bonds, the position of the substrate in the cavity of organocatalyst. In particular in this project were synthesized: · A wide class of monoprolinamide derivatives of bile acids, in order to find the right match between proline and cholestanic backbone. In particular synthesis of proline derivatives in different position of bile acid could throw light on the influence of position of proline moiety in the cholestanic emicavity on selectivity of organocatalyst. · A class of bisprolinamide derivatives of bile acids that could take advantage from the cooperative effect of two proline moieties. In designing synthesis of these derivatives attention has been paid to the use of low cost, easy and fast procedures in order to improve availability of the new organocatalysts. Activity and enantioselectivity of this new organocatalysts have been studied with particular attention to: · Aldol reaction · Michael reaction During the activity studies evaluation of parameters that can improve rate of different reaction (temperature, solvents, catalyst loading, reagents…) was considered. The possibility to carry out reactions in water and with very low catalyst loading was checked, in order to evaluate ecosostenibility of the chemical process. Experimental results were collected and analyzed with the help of conformational and computational studies.