Piperidine and octahydropyrano[3,4-c] pyridine scaffolds for drug-like molecular libraries of the European Lead Factory

Publication date: 1 October 2017
Source:Bioorganic & Medicinal Chemistry, Volume 25, Issue 19
Author(s): Bharat D. Narhe, Arjen C. Breman, Jalindar Padwal, Dirk A.L. Vandenput, Joeri M. Scheidt, Jorg C.J. Benningshof, Gijsbert A. van der Marel, Herman S. Overkleeft, Mario van der Stelt, Dmitri V. Filippov
We report short and efficient scalable syntheses of enantiomerically pure (3R,4S)-3-(hydroxymethyl4-(hydroxyethyl))-piperidine and 1-hydroxymethyl-octahydro-1H-pyrano[3,4-c]pyridine scaffolds. The alkaloid core was readily synthesized from naturally occurring quinine and can serve as a valued starting point for drug-discovery. Cleavage of a terminal 1,2-diol and acid catalysed epoxide opening cyclization are the key steps involved. A number of members of a projected small-molecular library is synthesized for each scaffold.

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