The invention is directed to isomeric mixtures of cyclosporine analogues thatare structurally similar to cyclosporine A. The mixtures possess enhancedefficacy and reduced toxicity over the individual isomers and over naturallyoccurring and other presently known cyclosporines and cyclosporinederivatives. Embodiments of the present invention are directed toward cis andtrans-isomers of cyclosporin A analogs referred to as ISATX247, andderivatives thereof. Mixtures of ISATX247 isomers exhibit a combination ofenhanced potency and reduced toxicity over the naturally occurring andpresently known cyclosporins. ISATX247 isomers and alkylated, arylated, anddeuterated derivatives are synthesized by stereoselective pathways where theparticular conditions of a reaction determine the degree of stereoselectivity.Stereoselective pathways may utilize a Wittig reaction, or an organometallicreagent comprising inorganic elements such as boron, silicon, titanium, andlithium. The ratio of isomers in a mixture may range from about 10 to 90percent by weight of the (E)-isomer to about 90 to 10 percent by weight of the(Z)-isomer, based on the total weight of the mixture.
