Invention Grant
US07799756B2 Processes for stereoselective synthesis of trans ISATX247 有权
用于立体选择性合成反式ISATX247的方法

Processes for stereoselective synthesis of trans ISATX247
Abstract:
The present invention relates to a process for preparation of a trans ISATX247 compound of the formula: where R1═H or D; R2═H or D; and R3═H or D, by application of organozirconium chemistry. The process involves reacting an acetyl cyclosporin aldehyde with an organozirconium reagent to provide acetyl cyclosporin diene (the acetate of trans ISATX247) and deacetylating the acetyl cyclosporin diene to produce the trans-isomer of ISATX247. The present invention also relates to a process for preparing the same trans ISATX 247 compound, using olefin cross metathesis. The process involves: olefin cross metathesis of acetyl cyclosporin A to afford acetyl cyclosporin α,β-unsaturated aldehyde; Wittig reaction of the acetyl cyclosporin α,β-unsaturated aldehyde to provide acetyl cyclosporin diene; and deacetylation of the acetyl cyclosporin diene to produce the trans ISATX247 compound. Also disclosed are processes for preparing an acetyl cyclosporin α,β-unsaturated aldehyde compound and a cyclosporin triene analogue compound.
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