Method for preparing a predetermined or non-predetermined isomeric mixture of cyclosporine analogs a modified in the 1-amino acid residue, method for producing an e-isomer or z-isomer enriched mixture of cyclosporin analogues a modified in the 1-amino acid residue, mixture of (e) and (z) -isomers, composition, method for stereoiselective synthesis of isatx247 z-isomer, method for the preparation of cyclosporine aldehyde a

摘要

"METHOD FOR PREPARING A PRE-DETERMINED ISOMERIC MIXTURE OR NOT FROM CYCLOSPORINE ANALOGS TO MODIFIED IN 1-AMINO ACID WASTE, METHOD FOR PRODUCTING AN ENRICHED MIXTURE WITH E-ISEMERO OR WITH AN ZAMYLAMIC RESIDUES , MIXTURE OF (E) AND (Z) -ISMEROS, COMPOSITION, METHOD FOR ISA Z-ISEMERE SYNTHESIS ~ TX ~ 247, METHOD FOR CYCLOSPORIN PREPARATION AND ALDEIDE ". The invention relates to isomeric mixtures of cyclosporine analogues that are structurally similar to cyclosporine A. The mixtures have greater efficacy and reduced toxicity relative to individual isomers and to naturally occurring cyclosporins and other currently known cyclosporins and derivatives thereof. of cyclosporine. Embodiments of the present invention relate to cis and trans isomers of the cyclosporin A analogs indicated as ISA-TX-247, and derivatives thereof. ISA-TX-247 isomers and alkylated, arylated and deuterated derivatives are synthesized by stereoselective pathways where the particular conditions of a reaction determine the degree of stereoselectivity. Stereoselective pathways may utilize a Wittig reaction, or an organometallic reagent comprising inorganic elements such as boron, silicon, titanium, and lithium. The ratio of isomers in a mixture may range from approximately 10 to 90 weight percent of the (E) -isomer to approximately 90 to 10 weight percent of the (Z) -isomer based on the total weight of the mixture.