Application of ring-closing metathesis for the synthesis of macrocyclic peptidomimetics as inhibitors of HCV NS3 protease.
An efficient synthetic approach for the preparation of macrocyclic peptidomimetics for inhibition of HCV NS3 is presented. The macrocyclic core is built using ring-closing metathesis (RCM) of a tripeptidic diene. The presented approach allows the introduction of heteroatoms in strategic places along the macrocyclic ring. The methyl ester moiety in the RCM products was synthetically manipulated to install a keto-amide moiety via a Passerini reaction.
Velázquez
Francisco
F
Schering-Plough Research Institute, 2015 Galloping Hill Road, K-15-3 3545, Kenilworth, New Jersey 07033-1300, USA. francisco.velazquez@spcorp.com
Venkatraman
Srikanth
S
Wu
Wanli
W
Blackman
Melissa
M
Prongay
Andrew
A
Girijavallabhan
Viyyoor
V
Shih
Neng-Yang
NY
Njoroge
F George
FG
D002384:Catalysis; D003500:Cyclization; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D016174:Hepacivirus / Q000201:enzymology*; D018716:Molecular Mimicry; D015394:Molecular Structure; D010455:Peptides / Q000737:chemistry*; D011758:Pyrroles / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology
D004791:Enzyme Inhibitors; D010455:Peptides; D011758:Pyrroles