Exhaustive Conformational Search for Sialyl Cation Reveals Possibility of Remote Participation of Acyl Groups.

Autor: Panova MV; Laboratory of Glycochemistry, N. D. Zelinsky Institute of Organic Chemistry, Russian Academy of Sciences, Leninsky prospect 47, 119991, Moscow, Russian Federation., Medvedev MG; Group of Theoretical Chemistry, N. D. Zelinsky Institute of Organic Chemistry, Russian Academy of Sciences, Leninsky prospect 47, 119991, Moscow, Russian Federation., Orlova AV; Laboratory of Glycochemistry, N. D. Zelinsky Institute of Organic Chemistry, Russian Academy of Sciences, Leninsky prospect 47, 119991, Moscow, Russian Federation., Kononov LO; Laboratory of Glycochemistry, N. D. Zelinsky Institute of Organic Chemistry, Russian Academy of Sciences, Leninsky prospect 47, 119991, Moscow, Russian Federation.
Jazyk: angličtina
Zdroj: Chemphyschem : a European journal of chemical physics and physical chemistry [Chemphyschem] 2022 Feb 04; Vol. 23 (3), pp. e202100788. Date of Electronic Publication: 2021 Dec 16.
DOI: 10.1002/cphc.202100788
Abstrakt: Finding convenient ways for the stereoselective α-sialylation is important due to the high practical significance of α-sialic acid-containing glycans and neoglycoconjugates. It was proposed that sialylation stereoselectivity is determined by the structure of the sialyl cation (also known in biochemistry as "sialosyl cation"), a supposed intermediate in this reaction. Here we design a new approach for studying the conformational space of highly flexible sialyl cation and find 1625 unique conformers including those stabilized by covalent remote participation (also known as long-range participation) of 4-O-acetyl (4-OAc), 5-N-trifluoroacetyl (5-NTFA), as well as 7,8,9-OAc from both α and β sides. The most energetically stable sialyl cation conformers are featured by 4-OAc participation, closely followed by 5-NTFA- and 7-OAc-stabilized conformers; unstabilized sialyl cation conformers are ∼10 kcal mol -1 less stable than the 4-OAc-stabilized ones. Analysis of all the obtained conformers by means of substituents positions, side chain conformations and ring puckering led us to a new "eight-conformer hypothesis" which describes interconversions among the most important sialyl cation conformers and predicts that stronger remote participation of acyl groups favors β-anomers. Thus, selective synthesis of the desired α-sialosides requires minimization of acyl groups participation.
(© 2021 Wiley-VCH GmbH.)
Databáze: MEDLINE
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