Destabilization of Glycosyl Cation by an Electron-Withdrawing Substituent at C-5 Makes Sialylation Reaction More α-Stereoselective

Zarina Z Mamirgova; Alexander I Zinin; Alexander A Chinarev; Alexander O Chizhov; Kirill P Birin; Nicolai V Bovin; Leonid O Kononov

doi:10.1021/acs.joc.4c02759

Destabilization of Glycosyl Cation by an Electron-Withdrawing Substituent at C-5 Makes Sialylation Reaction More α-Stereoselective

J Org Chem. 2025 Jan 10;90(1):931-937. doi: 10.1021/acs.joc.4c02759. Epub 2024 Dec 29.

Authors

Zarina Z Mamirgova¹, Alexander I Zinin¹, Alexander A Chinarev², Alexander O Chizhov¹, Kirill P Birin³, Nicolai V Bovin², Leonid O Kononov¹

Affiliations

¹ N.D. Zelinsky Institute of Organic Chemistry of the Russian Academy of Sciences, Leninsky prosp. 47, Moscow 119991, Russian Federation.
² M.M. Shemyakin-Yu.A. Ovchinnikov Institute of Bioorganic Chemistry of the Russian Academy of Sciences, Miklukho-Maklaya st. 16/10, Moscow 117997, Russian Federation.
³ Frumkin Institute of Physical Chemistry and Electrochemistry of the Russian Academy of Sciences, Leninsky prosp. 31-4, Moscow 119071, Russian Federation.

PMID: 39791133
DOI: 10.1021/acs.joc.4c02759

Abstract

Comparison of the reactivity of sialyl chlorides and bromides based on N-acetylneuraminic acid (Neu5Ac) and its deaminated analogue (KDN) in reactions with MeOH and i-PrOH without a promoter revealed that the acetoxy group at C-5 in a molecule of a sialic acid glycosyl donor can destabilize the corresponding glycosyl cation making the S_N1-like reaction pathway unfavorable. A change to the S_N2-like reaction pathway ensures preferential formation of the α-glycoside.