Comparative Study on the Effects of Picoloyl Groups in Sialylations Based on Their Substitution Pattern

Abstract

A novel 8-O-picoloylated sialyl donor has been developed, and the performance of various picoloylated sialyl donors in glycosylations with primary glycosyl acceptors has been evaluated. 8-O-Picoloyl and 4,9-di-O-picoloyl sialyl donors produced moderate to excellent yields of disaccharides with complete α-stereoselectivities. Synergistic effects between picoloyl and the accompanying O-protecting groups (benzoyl vs acetyl) were evaluated, as well as the effects of triflic acid concentration on the 8-O-picoloyl donor. 1H NMR analysis was also carried out to assess differences in the hydrogen-bonding net between sialyl donors.

Comparison of glycosyl donors: a supramer approach

“…As we know that the concentrations of reactants can affect the outcome of glycosylation [ 31 , 33 – 34 37 , 39 , 43 – 44 46 , 56 – 57 ], one must choose a concentration at which to perform the test glycosylation. This can be done either by analogy with similar reactions or by utilizing some rationalization, the second approach is more attractive.…”

“…However, the reliable installation of sialic acid residues in oligosaccharides is a rather difficult issue and poor predictability remains characteristic of the sialylation reaction [ 16 – 21 ]. As in other glycosylation reactions [ 22 – 29 ], the result of sialylation is affected by a variety of variables [ 30 – 39 ] including the nature of protective groups on either partner [ 26 , 38 , 40 – 45 ] and concentration of reagents [ 31 , 33 – 34 37 , 39 , 43 – 44 46 ].…”

Advanced Chemical Methods for Stereoselective Sialylation and Their Applications in Sialoglycan Syntheses

“…De Meo et al. reported that C4,C9‐di‐ O ‐picoloyl donor 113 and C8‐ O ‐picoloyl sialyl donor 114 exhibited complete α‐stereoselectivity [63b] . In many cases, picoloyl‐protected donors required an excess of TfOH (1.5–2.0 equiv.)…”

Influence of Remote Picolinyl and Picoloyl Stereodirecting Groups for the Stereoselective Glycosylation

“…They (2019) further extended their study to described the effects of picoloyl groups based on their position and number and also reported a novel synthesis of several mono-as well as di-O-picoloyl sialyl donors (127 to 132) to obtained disaccharides in moderate to excellent yields with better αstereoselectivities. [51] In support of their proposed strategy, they first used mono-picoloylated donors 127-130 activated by triflic acid and coupled with standard primary benzyl-protected galactosyl acceptors 2 to furnish the corresponding disaccharide (133 a-d) with α-selectivity exclusively. However, the complete α-selectivity obtained in the case of donor 129 while poor selectivity was obtained in the case of donor 130, and the case of donor 127 &128 moderate selectivity was observed.…”