ARS | Publication request: Novel Oxidation of Cyclosporin A: Preparation of Cyclosporin Methyl Vinyl Ketone (Cs-MVK)

Submitted to: Synlett
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: February 1, 2009
Publication Date: February 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.