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

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.

Citation

Maria V Panova, Michael G Medvedev, Anna V Orlova, Leonid O Kononov. Exhaustive Conformational Search for Sialyl Cation Reveals Possibility of Remote Participation of Acyl Groups. Chemphyschem : a European journal of chemical physics and physical chemistry. 2022 Feb 04;23(3):e202100788

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PMID: 34837303

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