| 摘要 |
The present invention relates to a process for preparation of a trans ISA<SUB>TX</SUB>247 compound of the formula: where R<SUB>1</SUB>-H or D; R<SUB>2</SUB>-H or D; and R<SUB>3</SUB>-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 ISA<SUB>TX</SUB>247) and deacetylating the acetyl cyclosporin diene to produce the trans-isomer of ISA<SUB>TX</SUB>247. The present invention also relates to a process for preparing the same trans ISA<SUB>TX </SUB>247 compound, using olefin cross metathesis. The process involves: olefin cross metathesis of acetyl cyclosporin A to afford acetyl cyclosporin alpha,beta-unsaturated aldehyde; Wittig reaction of the acetyl cyclosporin alpha,beta-unsaturated aldehyde to provide acetyl cyclosporin diene; and deacetylation of the acetyl cyclosporin diene to produce the trans ISA<SUB>TX</SUB>247 compound. Also disclosed are processes for preparing an acetyl cyclosporin alpha,beta-unsaturated aldehyde compound and a cyclosporin triene analogue compound.
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