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.

DOI: 10.1021/jo9021919

Cite this paper

@article{Thanh2010AVS, title={A versatile synthetic approach toward diversity libraries using monosaccharide scaffolds.}, author={Giang Le Thanh and Giovanni Abbenante and George W. Adamson and Bernd Becker and C. Clark and Glenn C Condie and Tania Falzun and Matthias Grathwohl and Praveer K. Gupta and Michael A. Hanson and Ngoc Anh Huynh and Peter L. Katavic and Krystle Kuipers and Ann Lam and Ligong Liu and Maretta Mann and Jeff Mason and Declan McKeveney and Craig A. Muldoon and Andrew P Pearson and Premraj Rajaratnam and Sarah T Ryan and Gerry Tometzki and Geraldine Verquin and Jennifer Waanders and Michael L. West and Neil L. Wilcox and Norbert Wimmer and Annika Yau and Johannes Zuegg and Wim Meutermans}, journal={The Journal of organic chemistry}, year={2010}, volume={75 1}, pages={197-203} }