1. A Highly Efficient Asymmetric Synthesis of Vernakalant
- Author
-
Eric R. Ashley, Gregory L. Beutner, Brendan Grau, Amude M. Kassim, Matthew D. Truppo, Jingjun Yin, John Limanto, Hallena R. Strotman, Zhijian Liu, Mary M. Kim, and Artis Klapars
- Subjects
chemistry.chemical_classification ,Pyrrolidines ,Molecular Structure ,Cyclohexane ,Transamination ,Stereochemistry ,Organic Chemistry ,Enantioselective synthesis ,Stereoisomerism ,Anisoles ,Ring (chemistry) ,Biochemistry ,Catalysis ,Pyrrolidine ,Vernakalant ,chemistry.chemical_compound ,Chlorides ,chemistry ,Cyclohexanes ,Zinc Compounds ,Stereoselectivity ,Amines ,Physical and Theoretical Chemistry ,Imide ,Amination - Abstract
A novel synthesis of vernakalant is described. Using inexpensive and readily available reagents, the key transformations involve (1) an efficient zinc-amine-promoted etherification, (2) a highly stereoselective enzyme-catalyzed dynamic asymmetric transamination to set up the two contiguous chiral centers in the cyclohexane ring, and (3) a pyrrolidine ring formation via alkyl-B(OH)2-catalyzed amidation and subsequent imide reduction.
- Published
- 2014
- Full Text
- View/download PDF