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. 2025 Apr 29;10(18):18700-18708.
doi: 10.1021/acsomega.5c00189. eCollection 2025 May 13.

Phenanthroline-Assisted Stereoselective Synthesis of 2-Deoxy Glycosides

Chun-Xiao Li  1 , Connor K English  1 , Daniil A Ahiadorme  1 , Hien M Nguyen  1
Affiliations

Phenanthroline-Assisted Stereoselective Synthesis of 2-Deoxy Glycosides

Chun-Xiao Li et al. ACS Omega. .

Abstract

The significance of 2-deoxy glycosides in biologically active compounds is well-established, as they frequently play a pivotal role in modulating the efficacy of therapeutic agents. The 2-deoxy sugar embodies a distinctive class of carbohydrates characterized by marked differences in stability, reactivity, and selectivity compared to their counterparts bearing C2-oxygen or other heteroatoms. As a result, the stereoselective synthesis of this carbohydrate class is complicated by its sensitivity to acidic conditions and propensity for hydrolysis and elimination reactions. Furthermore, the lack of C2-oxygen functionality presents an additional challenge in controlling stereoselectivity. In this study, we report the application of commercially available phenanthroline as an effective additive in the stereoselective glycosylation of aliphatic alcohols and phenolic nucleophiles with 2-deoxy glycosyl chlorides, facilitating efficient access to a variety of α-2-deoxy glycosides in high yields with synthetically useful stereoselectivity. Kinetic analyses suggest that phenanthroline plays a crucial role in modulating the selectivity of the reaction.

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Conflict of interest statement

The authors declare no competing financial interest.

Figures

Scheme 1
Scheme 1. Strategies for Stereoselective Preparation of α-2-Deoxy-O-glycosides
Scheme 2
Scheme 2. Kinetic Studies of the Glycosylation Reaction in the Presence and Absence of Phen Additive
See this image and copyright information in PMC

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