Synthesis of bis-macrocyclic HCV protease inhibitor MK-6325 via intramolecular sp²-sp³ Suzuki-Miyaura coupling and ring closing metathesis

Organic Letters
Hongmei LiLushi Tan

Abstract

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 sp(2)-sp(3) 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.

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Citations

Jul 12, 2016·Expert Opinion on Therapeutic Patents·Lin SunXinyong Liu

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