β-alanyl-L-Histidine β-alanyl-D-Histidine Hystidine and deuterium labelled hystidine by asymmetric catalytic reduction with gaseous H2 or D2; role of strong non coordinating acids. E.Cesarotti, I.Rimoldi, D. Zerla Università di Milano, Facoltà di Farmacia, Dipartimento di Chimica Inorganica, Metallorganica e Analitica. Natural carnosine β-alanyl-L-Histidine Unatural carnosine β-alanyl-D-Histidine Human serum carnosinase Cytotoxic compounds oxidative damage Non toxic products Carnosine is an endogenous dipeptide presents in the human muscles and nerve tissue. It has the ability to react with toxic aldehydes deriving from metabolic pathway of oxidative degradation of endogenous compounds and so it has a protective and detoxifying effect on the toxic metabolites. D-Carnosine is cited as an equivalent to L-carnosine, but due to its favourable pharmacokinetic properties, durability to hydrolysis by the carnosinases, and stability in the plasma, D-carnosine 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 to be distinguished by endogenous L-carnosine in LC–MS experiments. Non coordinating strong acid like HBF4 are necessary for the catalytic hydrogenation of (Z)-methyl 2-benzamido-3-(1H-imidazol-5-yl)acrylate (1); only when the ratio HBF4/substate is 4:1 or higher the reaction is quantitatively and highly stereoselective. The role of strong acid is the protonation of the basic nitrogen atom, which if not protonated, could coordinate to the metal giving a stable catalytically inactive complex. E. Cesarotti, I. Rimoldi, D. Zerla, G. Aldini; Tetrahedron: Asymmetry, Volume 19 (2008), Issue 3, 273-278. Commercially available ligands used in asymmetic hydrogenation; all reactions were performed in methanol at 293°K under 1 bar of H2 How type and ratio of non coordinating acids influence activity and enantioselectivity of the catalytic system? solvent Ratio Sub/acid 1/4 1/8 1/12 acid TOF (h-1) e.e. % HD % CH3OH HBF4 10.12 88 41.6 6.08 96 43.5 15.64 98 4.7 HClO4 4.77 86 45.3 10.37 91 41.9 3.0 20.9 CH3SO3H 1.71 93 47.2 6.02 94 40.0 2.26 97 32.6 CF3SO3H 4.57 84 43.3 12.51 33.4 18.78 80.7 CH3OD 5.85 89 19.16 18.39 95 18.75 3.50 11.08 4.61 1.02 0.98 35.68 28.63 34.64 Ratio Sub/acid 1/4 1/8 ligand acid TOF (h-1) e.e. % (R,R)-Me-DUPHOS HBF4 5.34 79 12.27 94 HClO4 16.91 84 11.51 90 CH3SO3H 5.52 98 2.78 CF3SO3H 24.68 99 27.10 93 (R)-PROLOPHOS 12.44 71 44.17 72 17.34 55 14.86 32 10.48 11.15 43 10.26 18 31.87 23 (S,S)-BDPP 7.42 68