Chiral synthons via combination of bio- and transition metal catalysis

The synergistic combination of bio- and transition metal catalysis leads to novel enantiomerically pure, highly functionalized oxygen and nitrogen heterocycles. Aminopeptidases are used for the synthesis of linear unsaturated amino acids, both in the (R)- and (S)-configuration, whereas lipases are used to generate enantiopure alcohols. The unsaturated amino acids are ideal precursors for Ru-catalyzed ring-closing olefin metathesis to form novel conformationally restricted highly functionalized cyclic amino acids in optically pure form. Acetylene-containing amino acids cart be transformed into novel heterocycles using Pd-catalyzed ring-closing and cross-coupling reactions. Linear unsaturated optically pure alcohols serve as starting materials for carbohydrate-like molecules using a combination of Pd- and Ru-catalysis. The resulting conformationally constrained, highly functionalized heterocycles are potential building blocks for pharmaceuticals and may be used in lead generation processes via combinatorial chemistry.