Stereo-controlled synthesis of functionalized tetrahydropyridines based on the cyanomethylation of 1,6-dihydropyridines and generation of anti-hepatitis C virus agents

Publication date: Available online 7 March 2017
Source:Bioorganic & Medicinal Chemistry
Author(s): Ryo Watanabe, Haruki Mizoguchi, Hideaki Oikawa, Hirofumi Ohashi, Koichi Watashi, Hiroki Oguri
Densely functionalized tetrahydropyridines were stereoselectively synthesized from 1,6-dihydropyridines. Exploiting a carbonyl group installed at the C3 position of the 1,6-dihydropyridine system, we devised a strategy for cyanomethylation at C2/C6 and subsequent divergent installation of an allyl group at C3/C5 in a highly regio- and stereo-controlled manner. This versatile protocol for programmable functionalization of the 1,6-dihydropyridine system allows the divergent and streamlined synthesis of multiply-substituted tetrahydropyridines as an important class of biologically and medicinally relevant scaffolds. Two of the N-heterocyclic compounds bearing an alkyl nitrile group showed anti-hepatitis C virus (HCV) activity.

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