Diastereoselective Synthesis of 2'-Dihalopyrimidine Ribonucleoside Inhibitors of Hepatitis C Virus Replication
Longhu Zhou1, Hongwang Zhang1, Chengwei Li1
1Center for AIDS Research, Laboratory of Biochemical Pharmacology, Department of Pediatrics, Emory University School of Medicine, and Children's Healthcare of Atlanta, 1760 Haygood Drive, Atlanta, Georgia 30322, United States.
Abstract:
We present a newly developed synthetic route to 2-bromo-2-fluoro ribolactone based on our published 2-chloro-2-fluoro ribolactone synthesis. Stereoselective fluorination is key to controlling the 2-diastereoselectivity. We also report a substantially improved glycosylation reaction with both the 2-bromo-2-fluoro and 2-chloro-2-fluoro sugars. These improvements allowed us to prepare 2'-dihalo nucleosides 13 and 14 in an overall 15-20% yield.
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