Total synthesis of cyclosporine: access to N-methylated peptides via isonitrile coupling reactions.
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.
Wu
Xiangyang
X
Laboratory for Bioorganic Chemistry, Sloan-Kettering Institute for Cancer Research, 1275 York Avenue, New York, New York 10065, USA.
Stockdill
Jennifer L
JL
Wang
Ping
P
Danishefsky
Samuel J
SJ
D000577:Amides / Q000737:chemistry; D016572:Cyclosporine / Q000138:chemical synthesis* / Q000737:chemistry; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000737:chemistry; D008745:Methylation; D015394:Molecular Structure; D009570:Nitriles / Q000737:chemistry*; D010455:Peptides / Q000737:chemistry*
D000577:Amides; D004791:Enzyme Inhibitors; D009570:Nitriles; D010455:Peptides; D016572:Cyclosporine