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ARS Home » Midwest Area » Peoria, Illinois » National Center for Agricultural Utilization Research » Renewable Product Technology Research » Research » Publications at this Location » Publication #254131
Title: Novel Oxidation of Cyclosporin A: Preparation of Cyclosporin Methyl Vinyl Ketone (Cs-MVK)

Author
item YANG, ZHICAI - Albany Molecular Research, Inc (AMRI)
item PATTAMANA, KEVIN - Albany Molecular Research, Inc (AMRI)
item MOLINO, BRUCE - Albany Molecular Research, Inc (AMRI)
item HAYDAR, SIMON - Albany Molecular Research, Inc (AMRI)
item CAO, YEYU - Albany Molecular Research, Inc (AMRI)
item BOIS, FREDERIC - Albany Molecular Research, Inc (AMRI)
item MAENG, JUN-HO - Albany Molecular Research, Inc (AMRI)
item HEMENWAY, MICHAEL - Albany Molecular Research, Inc (AMRI)
item Rich, Joseph
item KHMELNITSKY, YURI - Albany Molecular Research, Inc (AMRI)
item FRIEDRICH, THOMAS D - Albany Molecular Research, Inc (AMRI)
item PEACE, DENISE - Albany Molecular Research, Inc (AMRI)
item MICHELS, PETER C - Albany Molecular Research, Inc (AMRI)

Submitted to: Synlett
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 2/1/2009
Publication Date: 2/10/2009
Citation: Yang, Z., Pattamana, K., Molino, B.F., Haydar, S.N., Cao, Y., Bois, F., Maeng, J., Hemenway, M.S., Rich, J.O., Khmelnitsky, Y.L., Friedrich, T., Peace, D., Michels, P. 2009. Novel oxidation of Cyclosporin A: Preparation of Cyclosporin methyl vinyl ketone (Cs-MVK). Synlett. 18:2935-2938.

Interpretive Summary: Cyclosporin A, a naturally occurring cyclic peptide, possesses potent immunosuppressive activity and continues to be a first-line agent prescribed for the prevention of organ transplantation rejection. In addition, cyclosporin A and its analogues have demonstrated potential utility in other therapeutic areas, including psoriasis, asthma and other autoimmune disorders. The reactivity of a variety of biocatalysts on cyclosporin A was investigated to introduce functionality onto the cyclosporin A scaffold. A novel derivative is described that is a versatile synthetic intermediate that can be used for the preparation of many novel cyclosporine analogues that possess therapeutic potential as immunosuppressive agents.

Technical Abstract: Cyclosporin A (CsA) was converted into cyclosporin methyl vinyl ketone (Cs-MVK) by either a biocatalytic method utilizing 1-hydroxybenzotriazole-mediated laccase oxidation or by a chemical oxidation using t-butyl hydroperoxide and potassium ­periodate as co-oxidants. Cs-MVK is a novel, versatile synthetic intermediate that can be used for the preparation of many novel cyclosporin analogues possessing therapeutic potential as immunosuppressive agents.