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.
MeSH terms
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Catalysis
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Hepacivirus / drug effects
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Macrocyclic Compounds / chemical synthesis*
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Macrocyclic Compounds / chemistry
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Macrocyclic Compounds / pharmacology*
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Molecular Structure
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Protease Inhibitors / chemical synthesis*
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Protease Inhibitors / chemistry
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Protease Inhibitors / pharmacology*
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Viral Nonstructural Proteins / antagonists & inhibitors*
Substances
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MK-6325
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Macrocyclic Compounds
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NS3 protein, hepatitis C virus
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Protease Inhibitors
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Viral Nonstructural Proteins