Synthesis of chiral bioactive molecules by Catalytic Asymmetric Reduction

Synthesis of chiral bioactive molecules by Catalytic Asymmetric Reduction 1) Carnosine is an endogenous dipeptide (β-alanyl-L-histidine) presents in the human muscles and nerve tissue which has a protective and detoxifying effect on the toxic metabolites. D-Carnosine is cited as an equivalent to L-carnosine, but due to its durability to hydrolysis by the carnosinases, seems to produce better therapeutic results than the L-form. To study the bioavailability and pharmacokinetic profile of D-carnosine, a deuterium labelled derivative is needed. The optically active D or L histidine for carnosine synthesis can be preparated by asymmetric hydrogenation of the corresponding dehydro-aminoacid using Rh(I)-diphosphine complexes in presence of strong non coordinating acid. 2) The great success of Diphosphine-Ru systems in the reduction of funzionalized ketones was reappraised by low activity in the hydrogenation of un-funzionalized ketones which need the presence of an ancillary ligand in the complex for its reduction. In this thesis the effect of a rigid chirality on the ancillary diamine ligand using an ampy analogue, 8-amino-5,6,7,8-hydro-quinoline (CAMPY), will be studied in asymmetric hydrogenation and asymmetric transfer hydrogenation reactions.