The overall goal of the proposed research is to develop new, efficient synthetic methods using transition metal reagents and to apply these new methods to the synthesis of biologically active compounds, specifically amino acids and peptides, and nucleoside analogs. The specific aims of the proposed research in the area of amino acid and peptide chemistry are: (1) to complete the development of optically active chromium aminocarbene complexes as sources of natural and unnatural amino acid residues in peptide synthesis. This will involve primarily the synthesis of new carbene complexes; (2) to develop procedures to synthesize -amino acid activated esters via chromium carbene complex photochemistry, to permit the introduction of unusual amino acid residues into classic peptide synthetic methodology; (3) to develop procedures for the unusual coupling of two peptide fragments through a single amino acid residue to produce symmetrical and unsymmetrical pseudopeptides. The specific aims of the proposed research in the area of nucleoside analog chemistry are: (1) to develop procedures to convert cyclobutanone-derived optically active butyrolactones and butenolides into a very wide range of differently substituted nucleoside analogs, particularly those having 4'- disubstitution, (2) to develop cyclobutanone ring expansion procedures to synthesize carbocyclic nucleoside analogs, as well as C-nucleoside analogs, (3) to expand these newly developed procedures for the synthesis of psicofuranine and decoynine analogs as well as their carbocyclic analogs, (4) to develop procedures to synthesize unusual 4'-disubstituted nucleoside analogs via cyclobutanone photochemistry. All of these procedures will provide equal access to either enantiomer, an important feature since the "unnatural- enantiomer of a nucleoside analog may be more active and less toxic then the "natural" one.