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ABSTRACT: We describe herein our recent explorations in the field of isonitrile chemistry. An array of broadly useful coupling methodologies has been developed for the formation of peptidyl and glycopeptidyl amide bonds. We further describe the application of these methods to the syntheses of complex systems, including the cyclic peptide cyclosporine A, constrained peptide systems, and heterocycles.
Angewandte Chemie International Edition 02/2012; 51(12):2834-48. · 13.45 Impact Factor
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ABSTRACT: The scope of isonitrile-mediated amide bond-forming reactions is further explored in this second-generation synthetic approach to cyclosporine (cyclosporin A). Both type I and type II amidations are utilized in this effort, allowing access to epimeric cyclosporins A and H from a single precursor by variation of the coupling reagents. This work lends deeper insight into the relative acylating ability of the formimidate carboxylate mixed anhydride (FCMA) intermediate, while shedding light on the far-reaching impact of remote stereochemical changes on the effective preorganization of seco-cyclosporins.
Journal of the American Chemical Society 02/2012; 134(4):2378-84. · 9.91 Impact Factor
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ABSTRACT: Recent developments in the use of isonitriles to furnish secondary and tertiary amide bond formations have been applied to a novel total synthesis of the important cyclic polypeptide cyclosporine A. Specifically, the disclosed synthetic route demonstrates the utility of microwave-mediated carboxylic acid isonitrile couplings, thioacid isonitrile couplings at ambient temperature, and isonitrile-mediated couplings of carboxylic acids and thioacids with amines to form challenging amide bonds.
Journal of the American Chemical Society 03/2010; 132(12):4098-100. · 9.91 Impact Factor
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ABSTRACT: The coupling reaction between hindered thioacids and isonitriles is developed and described. The mechanism for the formation of the thiopyruvamide products is explored, and the method is applied to a selection of substrates.
Tetrahedron Letters 09/2009; 50(36):5152-5155. · 2.68 Impact Factor
