Exhaustive conformational search for sialyl cation reveals possibility of remote participation of acyl groups

Chemphyschem. 2021 Nov 26. doi: 10.1002/cphc.202100788. Online ahead of print.ABSTRACTFinding convenient ways for the stereoselective α-sialylation is important due to the high practical significance of α-sialic acid-containing glycans and neoglycoiconjugates. 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-OAc, 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 favor β-anomers. Thus, selective synthesis of the desired α-sialosides requires minimization of acyl groups participation.PMID:34837303 | DOI:10.1002/cphc.202100788

Source: Chemphyschem - November 27, 2021 Category: Chemistry Authors: Maria V Panova Michael G Medvedev Anna V Orlova Leonid Kononov Source Type: research