Patent ID: 7141648
Filing Date: 2006-11-28
Classification: A61K,A61P,B82Y,C07K,Y10S

Abstract:
1. A method of preparing an isomeric mixture of cyclosporin A analogs modified at the 1-amino acid residue, wherein the synthetic pathway comprises the steps of: a) protecting the β-alcohol of cyclosporin A by forming a first intermediate acetyl cyclosporin A; b) oxidizing the acetyl cyclosporin A to produce a second intermediate acetyl cyclosporin A aldehyde, wherein the oxidizing step is carried out with ozone and is an ozonolysis and further wherein the ozonolysis also comprises treatment with a reducing agent; c) converting an intermediate acetyl cyclosporin A aldehyde to a mixture of (E) and (Z)-isomers of acetyl-1,3-diene by reacting the intermediate with a phosphorus ylide via a Wittig reaction, optionally in the presence of a lithium halide; and d) preparing a mixture of (E) and (Z)-isomers of cyclosporin A analogs modified at the 1-amino acid residue by treating the mixture of(E) and (Z)-isomers of acetyl-1,3-diene with a base, wherein the reducing agent is tributyl phosphine.