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NO Bond as a Glycosidic‐Bond Surrogate: Synthetic Studies Toward Polyhydroxylated N ‐Alkoxypiperidines
Author(s) -
Malik Gaëlle,
Ferry Angélique,
Guinchard Xavier,
Cresteil Thierry,
Crich David
Publication year - 2013
Publication title -
chemistry – a european journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.687
H-Index - 242
eISSN - 1521-3765
pISSN - 0947-6539
DOI - 10.1002/chem.201202374
Subject(s) - chemistry , glycosidic bond , reductive amination , double bond , alkoxy group , stereochemistry , sodium cyanoborohydride , ring (chemistry) , hydrolysis , amination , organic chemistry , alkyl , enzyme , catalysis
A series of novel polyhydroxylated N ‐alkoxypiperidines has been synthesized by ring‐closing double reductive amination (DRA) of highly functionalized 1,5‐dialdehydes with various hydroxylamines. The required saccharide‐based dialdehydes were prepared efficiently from sodium cyclopentadienylide in seven steps. A two‐step protocol has been developed for the DRA; it led, after deprotection, to isofagomine, 3‐deoxyisofagomine, and numerous other N ‐alkoxy analogues. The barrier to inversion in these polyhydroxylated N ‐alkoxypiperidine derivatives was found by variable‐temperature NMR methods to be approximately 15 kcal mol −1 . With the exception of N ‐hydroxyisofagomine itself, none of the compounds prepared showed significant inhibitory activity against sweet almond β‐glucosidase.