Stabilization of sialyl cation in axial conformation assisted by remote acyl groups

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

“…Considering the existence of sialic acid 2,7-anhydro derivative, [50,51] as well as 1,4 [52] -and 1,7-lactones [52][53][54][55] in our previous work [43] we suggested that all-axial conformation (AX, Figure 2) of the model sialyl cation 1 may influence the outcome of sialylation reaction due to remote participation of acyl groups. Preliminary computational results agreed with our supposition: conformers 4 and 7 were found to be more [43] and B -minimal energy structures obtained after conformational search and subsequent DFT calculations in this work (PBE0-D3/6-31G*, PCM (MeCN), structures minE, minAX, min4, min5, min7α, min7β, min8α, min8β, min9α, and min9β). 3D pictures of structures obtained in this work are depicted in Figures S5-S14, their coordinates are provided in Tables S2-S11, MinConf.xyz file and their energies and some other properties are given in Table S1.…”

“…Thus, it was earlier shown that sialyl cation can adopt all-axial conformation ( 5 H 4 ). [36] On the basis of this in our previous work [43] we have suggested the possibility of remote group participation in sialyl cation. However, the analysis of all the 1625 conformers obtained here by means of changing positions of substituents (axial/equatorial), side chain conformations and ring puckering allowed us to make the following adjustments:…”

“…[44][45][46][47] These calculations showed feasibility of remote participation of acyl protective groups at O4, N5, O7, O8 and O9 (Figure 2, structures 4, 5, 7, 8 and 9) along with great dependence of the resulting conformers on starting geometries. [43] However, a reliable model should account for all possible glycosyl cation conformations, so it is important to maximize the number of starting geometries as it was done for the glycosyl cations of glucose, galactose and mannose with the genetic algorithm employed for the comparison of experimental and predicted IR spectra. [48] For the sialyl cation, a sufficient conformational analysis is even more critical due to the high flexibility of the glycerol side chain.…”

“…However, of greatest interest are the structures that are close to those involved in sialylation reactions in carbohydrate chemistry. Thus, in our recent work [43] we performed DFT calculations of a model per‐ O ‐acetyl (OAc) sialyl cation 1 with 5‐ N ‐trifluoroacetyl (5‐NTFA) group (Figure 1). Trifluoroacetyl group at N5 was chosen because a number of successful syntheses of naturally occurring sialyl derivatives was efficiently performed using 5‐NTFA‐protected sialyl donors [44–47] …”

“… Structures of different types of conformations of the model sialyl cation 1 : A – obtained in our previous work (PBE0‐D3/cc‐pVDZ, SMD (MeCN), structures E , AX , 4 , 5 , 7 , 8 and 9 ); [43] and B – minimal energy structures obtained after conformational search and subsequent DFT calculations in this work (PBE0‐D3/6‐31G*, PCM (MeCN), structures minE , minAX , min4 , min5 , min7α , min7β , min8α , min8β , min9α , and min9β ). 3D pictures of structures obtained in this work are depicted in Figures S5–S14, their coordinates are provided in Tables S2–S11, MinConf.xyz file and their energies and some other properties are given in Table S1.…”