Expanding the limits of isonitrile-mediated amidations: on the remarkable stereosubtleties of macrolactam formation from synthetic seco-cyclosporins

J Am Chem Soc. 2012 Feb 1;134(4):2378-84. doi: 10.1021/ja2103372. Epub 2012 Jan 17.


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amides / chemistry*
  • Cyclosporins / chemistry*
  • Lactams, Macrocyclic / chemical synthesis*
  • Lactams, Macrocyclic / chemistry
  • Molecular Structure
  • Nitriles / chemistry*
  • Stereoisomerism


  • Amides
  • Cyclosporins
  • Lactams, Macrocyclic
  • Nitriles