title: A versatile synthetic approach toward diversity libraries using monosaccharide scaffolds.
abstract: The pyranose scaffold is unique in its ability to position pharmacophore substituents in various ways in 3D space, and unique pharmacophore scanning libraries could be envisaged that focus on scanning topography rather than diversity in the type of substituents. Approaches have been described that make use of amine and acid functionalities on the pyranose scaffolds to append substituents, and this has enabled the generation of libraries of significant structural diversity. Our general aim was to generate libraries of pyranose-based drug-like mimetics, where the substituents are held close to the scaffold, in order to obtain molecules with better defined positions for the pharmacophore substituents. Here we describe the development of a versatile synthetic route toward peptide mimetics build on 2-amino pyranose scaffolds. The method allows introduction of a wide range of substituent types, it is regio- and stereospecific, and the later diversity steps are performed on solid phase. Further, the same process was applied on glucose and allose scaffolds, in the exemplified cases, and is likely adaptable to other pyranose building blocks. The methods developed in this work give access to molecules that position the three selected binding elements in various 3D orientations on a pyranose scaffold and have been applied for the production of a systematically diverse library of several hundred monosaccharide-based mimetics.
authors: Alchemia Ltd., Eight Mile Plains, Queensland 4113, Australia.
authors: Giang Le
authors: GL
authors: Thanh
authors: Giovanni
authors: G
authors: Abbenante
authors: George
authors: G
authors: Adamson
authors: Bernd
authors: B
authors: Becker
authors: Chris
authors: C
authors: Clark
authors: Glenn
authors: G
authors: Condie
authors: Tania
authors: T
authors: Falzun
authors: Matthias
authors: M
authors: Grathwohl
authors: Praveer
authors: P
authors: Gupta
authors: Michael
authors: M
authors: Hanson
authors: Ngoc
authors: N
authors: Huynh
authors: Peter
authors: P
authors: Katavic
authors: Krystle
authors: K
authors: Kuipers
authors: Ann
authors: A
authors: Lam
authors: Ligong
authors: L
authors: Liu
authors: Maretta
authors: M
authors: Mann
authors: Jeff
authors: J
authors: Mason
authors: Declan
authors: D
authors: McKeveney
authors: Craig
authors: C
authors: Muldoon
authors: Andrew
authors: A
authors: Pearson
authors: Premraj
authors: P
authors: Rajaratnam
authors: Sarah
authors: S
authors: Ryan
authors: Gerry
authors: G
authors: Tometzki
authors: Geraldine
authors: G
authors: Verquin
authors: Jennifer
authors: J
authors: Waanders
authors: Michael
authors: M
authors: West
authors: Neil
authors: N
authors: Wilcox
authors: Norbert
authors: N
authors: Wimmer
authors: Annika
authors: A
authors: Yau
authors: Johannes
authors: J
authors: Zuegg
authors: Wim
authors: W
authors: Meutermans
mesh_terms: D000588:Amines / Q000737:chemistry*; D020650:Combinatorial Chemistry Techniques; D006031:Glycosylation; D009682:Magnetic Resonance Spectroscopy; D015394:Molecular Structure; D009005:Monosaccharides / Q000138:chemical synthesis* / Q000737:chemistry*; D010455:Peptides / Q000138:chemical synthesis* / Q000737:chemistry*; D013400:Sugar Acids / Q000138:chemical synthesis* / Q000737:chemistry*
chemical_list: D000588:Amines; D009005:Monosaccharides; D010455:Peptides; D013400:Sugar Acids