Solid-Phase Total Synthesis of Cyclosporine Analogues

✍ Scribed by Soo Y. Ko; Roland M. Wenger

• Publisher: John Wiley and Sons
• Year: 1997
• Tongue: German
• Weight: 645 KB
• Volume: 80
• Category: Article
• ISSN: 0018-019X
• DOI: 10.1002/hlca.19970800307

✦ Synopsis

Syntheses of cyclosporine analogues are reported wherein the peptide couplings were achieved in solid phase.

The Wang resin was used as the solid support, and the peptide couplings commenced with the residue 11 of the cyclosporine skeleton. The couplings proceeded in a stepwide manner up to the residue MeBmt', using symmetric anhydrides. The peptides were then cleaved off the resin, and the cyclization was achieved in solution using Castro's reagent. The solid-phase synthesis described herein offers a very efficient method for the rapid synthesis of structurally diverse cyclosporine analogues in small quantities. The biological activities of the synthetic cyclosporine analogues were evaluated in two in virro assays, including the IL-2 reporter gene assay and the cyclophilin binding assay. The structure-activity relationship is discussed.

' ) The introduction of a D-MeAla residue at position 3 of CS has a stabilizing effect on the bioactive CS conformation 1221.