title: Expanding the limits of isonitrile-mediated amidations: on the remarkable stereosubtleties of macrolactam formation from synthetic seco-cyclosporins.
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.
authors.affiliation: Laboratory for Bioorganic Chemistry, Sloan-Kettering Institute for Cancer Research, 1275 York Avenue, New York, New York 10065, USA.
authors.forename: Xiangyang
authors.initials: X
authors.lastname: Wu
authors.forename: Jennifer L
authors.initials: JL
authors.lastname: Stockdill
authors.forename: Peter K
authors.initials: PK
authors.lastname: Park
authors.forename: Samuel J
authors.initials: SJ
authors.lastname: Danishefsky
mesh_terms: D000577:Amides / Q000737:chemistry*; D003524:Cyclosporins / Q000737:chemistry*; D047029:Lactams, Macrocyclic / Q000138:chemical synthesis* / Q000737:chemistry; D015394:Molecular Structure; D009570:Nitriles / Q000737:chemistry*; D013237:Stereoisomerism
chemical_list: D000577:Amides; D003524:Cyclosporins; D047029:Lactams, Macrocyclic; D009570:Nitriles