Synthesis of Bis-Macrocyclic HCV Protease Inhibitor
MK-6325 via Intramolecular sp2–sp3 Suzuki–Miyaura Coupling and Ring Closing
Metathesis

Li, Hongmei; Scott, Jeremy P.; Chen, Cheng-yi; Journet, Michel; Belyk, Kevin; Balsells, Jaume; Kosjek, Birgit; Baxter, Carl A.; Stewart, Gavin
W.; Wise, Christopher; Alam, Mahbub; Song, Zhiguo Jake; Tan, Lushi

doi:10.1021/acs.orglett.5b00418.s001

Synthesis of Bis-Macrocyclic HCV Protease Inhibitor MK-6325 via Intramolecular sp²–sp³ Suzuki–Miyaura Coupling and Ring Closing Metathesis

journal contribution

posted on 2015-03-20, 00:00 authored by Hongmei Li, Jeremy P. Scott, Cheng-yi Chen, Michel Journet, Kevin Belyk, Jaume Balsells, Birgit Kosjek, Carl A. Baxter, Gavin W. Stewart, Christopher Wise, Mahbub Alam, Zhiguo Jake Song, Lushi Tan

A practical asymmetric synthesis of the complex fused bis-macrocyclic HCV protease inhibitor MK-6325 (1) is described. Through the combination of a high yielding and low catalyst loading ring-closing metathesis (RCM) to forge the 15-membered macrocycle with an intramolecular sp²–sp³ Suzuki–Miyaura cross-coupling to append the 18-membered macrocycle, multikilogram access to the unique and challenging architecture of MK-6325 (1) has been achieved.