Piperidine and octahydropyrano[3, 4-c] pyridine scaffolds for drug-like molecular libraries of the European Lead Factory. Issue 19 (1st October 2017)

• Record Type: Journal Article
• Authors: Narhe, Bharat D.; Breman, Arjen C.; Padwal, Jalindar; Vandenput, Dirk A.L.; Scheidt, Joeri M.; Benningshof, Jorg C.J.; van der Marel, Gijsbert A.; Overkleeft, Herman S.; van der Stelt, Mario; Filippov, Dmitri V.
• Is Part Of: Bioorganic & medicinal chemistry. Volume 25:Issue 19(2017)
• Page Start: 5160
• Page End: 5170
• Publication Date: 2017-10-01
• Subjects: Nitrogen heterocycles -- Compound libraries -- Quinine -- 1, 3-Amino alcohols -- Non-racemic scaffolds; Bioorganic chemistry -- Periodicals; Pharmaceutical chemistry -- Periodicals; Biochemistry -- Periodicals; Chemistry, Clinical -- Periodicals; Chemistry, Organic -- Periodicals; Chimie bio-organique -- Périodiques; Chimie pharmaceutique -- Périodiques; 615.19
• DOI: 10.1016/j.bmc.2017.07.016
• Languages: English
• ISSNs: 0968-0896

Abstract

Graphical abstract: Abstract: We report short and efficient scalable syntheses of enantiomerically pure (3 R, 4 S )-3-(hydroxymethyl4-(hydroxyethyl))-piperidine and 1-hydroxymethyl-octahydro-1 H -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.