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Solid‐Phase Total Synthesis of Cyclosporine Analogues
Author(s) -
Ko Soo Y.,
Wenger Roland M.
Publication year - 1997
Publication title -
helvetica chimica acta
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.74
H-Index - 82
eISSN - 1522-2675
pISSN - 0018-019X
DOI - 10.1002/hlca.19970800307
Subject(s) - chemistry , solid phase synthesis , residue (chemistry) , peptide synthesis , peptide , reagent , combinatorial chemistry , in vitro , stereochemistry , total synthesis , cyclic peptide , biochemistry , organic chemistry
Abstract 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 1 , 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 vitro assays, including the IL‐2 reporter gene assay and the cyclophilin binding assay. The structure‐activity relationship is discussed.