通过分子内sp²-sp³铃木-宫浦偶联反应和关环复分解反应合成双大环丙型肝炎病毒蛋白酶抑制剂MK-6325。
Synthesis of bis-macrocyclic HCV protease inhibitor MK-6325 via intramolecular sp²-sp³ Suzuki-Miyaura coupling and ring closing metathesis.
作者信息
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
机构信息
†Department of Process Chemistry, Merck Research Laboratories, P.O. Box 2000, Rahway, New Jersey 07065, United States.
出版信息
Org Lett. 2015 Mar 20;17(6):1533-6. doi: 10.1021/acs.orglett.5b00418. Epub 2015 Mar 10.
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.
描述了复杂的稠合双大环 HCV 蛋白酶抑制剂 MK-6325（1）的实用不对称合成方法。通过高产率且低催化剂负载量的闭环复分解反应（RCM）形成 15 元大环，并结合分子内 sp(2)-sp(3) 铃木-宫浦交叉偶联反应来连接 18 元大环，已实现了多千克规模地合成具有独特且具有挑战性结构的 MK-6325（1）。
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