Solvent-free, under air selective synthesis of α-glycosides adopting glycosyl chlorides as donors
α-Glycosides are highly relevant synthetic targets due to their abundance in natural oligosaccharides involved in many biological processes. Nevertheless their preparation is hampered by several issues, due to both the strictly anhydrous conditions typically required in glycosylation procedures and...
Saved in:
Published in | Organic & biomolecular chemistry Vol. 18; no. 27; pp. 5157 - 5163 |
---|---|
Main Authors | , , , |
Format | Journal Article |
Language | English |
Published |
CAMBRIDGE
Royal Soc Chemistry
15.07.2020
Royal Society of Chemistry |
Subjects | |
Online Access | Get full text |
Cover
Loading…
Summary: | α-Glycosides are highly relevant synthetic targets due to their abundance in natural oligosaccharides involved in many biological processes. Nevertheless their preparation is hampered by several issues, due to both the strictly anhydrous conditions typically required in glycosylation procedures and the non-trivial achievement of high α-stereoselectivity, one of the major challenges in oligosaccharide synthesis. In this paper we report a novel and efficient approach for the highly stereoselective synthesis of α-glycosides. This is based on the unprecedented solvent-free combination of triethylphosphite, tetrabutylammonium bromide and
N
,
N
-diisopropylethylamine for the activation of glycosyl chlorides under air. Despite the relative stability of glycosyl chlorides with respect to more reactive halide donors, the solvent-free procedure allowed a wide set of α-glycosides, including biorelevant fragments, to be obtained in much shorter times compared with similar glycosylation approaches in solution. The presented method features a wide target scope and functional group compatibility, also serving with partially disarmed substrates, and it does not require a high stoichiometric excess of reagents nor the preparation of expensive precursors. The solvent-free glycosylation can be even directly performed from 1-hydroxy sugars without purification of the
in situ
generated chloride, providing an especially useful opportunity in the case of highly reactive and labile glycosyl donors.
A solvent-free, under air approach for the highly stereoselective synthesis of α-glycosides from glycosyl chloride donors, promoted by a triethylphosphite, tetrabutylammonium bromide, and
N
,
N
-diisopropylethylamine combination. |
---|---|
Bibliography: | 10.1039/d0ob01024c Electronic supplementary information (ESI) available: Synthesis of glycosyl donors and acceptors and characterization of the obtained products including copies of NMR spectra. See DOI ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 |
ISSN: | 1477-0520 1477-0539 |
DOI: | 10.1039/d0ob01024c |