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Benzoylation of Tetrols: A Comparison of Regioselectivity Patterns for O- and S- Glycosides of d-Galactose.
- Source :
-
The Journal of organic chemistry [J Org Chem] 2024 Sep 12. Date of Electronic Publication: 2024 Sep 12. - Publication Year :
- 2024
- Publisher :
- Ahead of Print
-
Abstract
- Efficient protecting group strategies are important for glycan synthesis and represent a unique synthetic challenge in differentiating sugar ring hydroxyl groups. Direct methods to enable regioselective protecting group installation are thus desirable. Herein, we explore a one-step regioselective benzoylation to deliver 2,3,6-protected d-galactose building blocks from tetrols across a variety of α- and β-, O - and S -glycoside substrates. We focus on benzoyl chloride as the esterifying reagent and a reaction temperature of -40 °C to screen the regioselectivity outcome for twenty-two different glycosides, based on isolated yields. Using this methodology, we demonstrate the capability for α-linked aryl and alkyl glycosides ( O - and S - d-galactosides, d-galactosamines, and l-fucose), delivering consistent isolated yields (>65%) for 2,3,6-benzoylated products. We extend to explore β-linked systems, where the observed regioselectivity is not paralleled. We posit that both steric and electronic factors from the anomeric substituent contribute to modulating the reactivity competition between 2-OH and 4-OH, enabling the formation of regioisomeric mixtures. However, a certain balance of these factors within the aglycon can deliver 2,3,6-regioselectivity, notably for β-O -Et and β-O -CH <subscript>2</subscript> CF <subscript>3</subscript> glycosides. The methodology contributes toward understanding the peculiarities of regioselective carbohydrate-protecting group installation, exploring the importance of the anomeric substituent upon ring hydroxyl group reactivity.
Details
- Language :
- English
- ISSN :
- 1520-6904
- Database :
- MEDLINE
- Journal :
- The Journal of organic chemistry
- Publication Type :
- Academic Journal
- Accession number :
- 39265180
- Full Text :
- https://doi.org/10.1021/acs.joc.4c01508