Synthesis of 2-Deoxyglycosides Bearing Free Hydroxyl Substituents on the Glycosyl Donor
Year: 2022
Type: article
Abstract: Recent efforts in the field of carbohydrate chemistry have focused on the site- and stereocontrolled synthesis of O -glycosides derived from acceptors bearing multiple hydroxyl substituents. By comparison, there are few examples of the site-selective synthesis of O -glycosides bearing free hydroxyl substituents on the donor reagent. Here, we report the application of an umpolung glycosylation strategy to the synthesis of O -glycosides derived from donors bearing free hydroxyl substituents. The reaction proceeds via prior deprotonation of one or more free hydroxyl groups on a thiophenylglycoside donor, reductive lithiation to generate an anomeric anion intermediate, and addition of this anion to an alkyl 2-(2-methyltetrahydropyranyl) peroxide. By this approach, α-linked glycosides were obtained in 39–84% yields and with >50:1 α/β selectivities. In many instances, β-linked products could be obtained by thermal equilibration of the anomeric anion intermediate (selectivities = 3.8–8:1 β/α; yields = 33–68%). The strategy is applicable to polyhydroxyl donors bearing up to three free hydroxyl groups, N -acylated carbohydrates, and the single-flask syntheses of oligosaccharides.
Source: The Journal of Organic Chemistry
Authors: Kevin M. Hoang, Xiaoying Zheng, Seth B. Herzon
Institution: Yale University
Language: English
Subfield: Organic Chemistry
Field: Chemistry
Domain: Physical Sciences
Open Access status: green
OpenAlex ID: W4289653985