Organozirconium Chemistry On Cyclosporin: A Novel Process For The Highly Stereoselective Synthesis Of (E)-Isa247 (Voclosporin) And Close Analogues
Synthesis(2012)
Abstract
Application of organozirconium chemistry to cyclosporin has led to the development of a novel process for the highly stereoselective synthesis of the E-isomer of ISA247 (voclosporin), which is a potent immunosuppressive agent currently in late stage human clinical trials for treatment of psoriasis, prevention of kidney transplant rejection, and ophthalmic indications. Synthesis of deuterated analogues of ISA247 and a cyclosporin triene analogue using the same methodology is also described.
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Key words
cyclosporin A, ISA247, voclosporin, E-diene, organozirconium chemistry
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