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Synfacts 2022; 18(09): 1041
DOI: 10.1055/s-0041-1738561
Innovative Drug Discovery and Development

Isonitrile Couplings Enable a Modular Synthesis of Cyclosporin A

Contributor(s):
Dirk Trauner
,
Matthew DiCairano
Wu X, Stockdill JL, Wang P, Danishefsky SJ. * Sloan-Kettering Institute for Cancer Research and Columbia University, New York, USA
Total Synthesis of Cyclosporine: Access to N-Methylated Peptides via Isonitrile Coupling Reactions.

J. Am. Chem. Soc. 2010;
132: 4098-4100
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Key words

cyclosporine A - isonitrile coupling - Lawesson’s reagent

Significance

Cyclosporin A is a reversible inhibitor of cytokines in T helper cells. Clinically, it is used as an immunosuppressant, allowing for otherwise non-sustainable organ transplants. Additionally, it is used to treat rheumatoid arthritis and Crohn’s disease.


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Comment

Novel isonitrile couplings were used to form peptide bonds. A nucleophilic addition yielded a thio-formimidate mixed anhydride, which underwent a 1,3-O→N acyl shift to generate an N-thioformyl amide.


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Publication History

Article published online:
18 August 2022

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