A Study on the Influence of the Structure of the Glycosyl Acceptors on the Stereochemistry of the Glycosylation Reactions with 2‐Azido‐2‐Deoxy‐Hexopyranosyl Trichloroacetimidates

Abstract

The stereochemical outcome of glycosylations with 2-azido-2-deoxy-D-gluco- and D-galactopyranosyl trichloroacetimidates as glycosyl donors has been investigated by using a series of chiro-inositol derivatives as glycosyl acceptors. The influence of the absolute configuration, the conformation and the conformational flexibility of the glycosyl acceptor has been studied by using different glycosyl donors under similar pre-established experimental conditions. Although the structure of the acceptor may play a role in governing the stereochemistry of these glycosylations, the results show that, in general terms, the relative influence of these factors is difficult to evaluate. For a given set of experimental conditions, the stereochemical course of these glycosylations depends on structural features of both glycosyl donor and glycosyl acceptor. It is a balance of these factors, where the structure of the glycosyl donor always plays a major role, which determines the stereochemistry of the coupling reaction. Therefore, the examples reported in the literature in which the structure of the glycosyl acceptor appears to be crucial in determining the stereochemistry of the reaction constitute particularly favorable cases which do not presently allow any further generalization.

A propos of glycosyl cations and the mechanism of chemical glycosylation

“…Probing of the existence of diastereomeric matching and mismatching, through the use of an enantiomeric pair of acceptors with an enantiomerically pure donor or the converse [93], might be considered as another possible entry into determining the extent of involvement of the acceptor in a glycosylation reaction. For example, a pair of coupling reactions exhibiting a high degree of diastereomeric discrimination as in the coupling of perbenzoyl Dand L-fucosyl bromides (D-3 and L-3) with the Dglucosamine based acceptor D-4 resulting in two sets of two anomers (Scheme 8) [93] must be considered as having a relatively tight transition state, whereas one with little or no such discrimination, as in the coupling of the enantiomeric chiro-inositol acceptors D-and L-6 with the D-2-azido-2-deoxy glucopyranosyl trichloroacetimidate donor D-7 (Scheme 9) [94], necessarily is highly exploded.…”

Stereoselectivity of Conformationally Restricted Glucosazide Donors

“…The extrapolation of the stereoselectivity of benzylidene glucose donors to their glucosazide counterparts suggests that benzylidene or analogously protected glucosazides might represent an attractive class of 1,2- cis -selective glucosamine donor synthons. 20,21 …”

“…The in-depth research conducted on conformationally restricted benzylidene mannose and glucose donors has provided important insight into the glycosylation mechanisms of this type of 1,2- cis -selective donor. − To construct 1,2- cis linkages of glucosamine donors, the C-2-amino group is most commonly masked as the nonparticpating azide. , Notably, benzylidene glucosazides have not been systematically investigated with respect to the stereoselectivity of glycosylations in which they are employed. The extrapolation of the stereoselectivity of benzylidene glucose donors to their glucosazide counterparts suggests that benzylidene or analogously protected glucosazides might represent an attractive class of 1,2- cis -selective glucosamine donor synthons. , …”

Armed-Disarmed Concept in the Synthesis of Glycosidic Bond

“…5.34) with different glycosyl donors, in particular 2-azido-2-deoxy-glycopyranosyl trichloroacetimidates. In an attempt to extend the applicability of the double stereodifferentiation principle [59] to glycosylation reactions [60], Martin-Lomas et al studied the stereoselectivity of the glycosylation of D-and L-chiro-inositol derivatives with several glycosyl donors [61]. The authors observed that when differently protected 1,2-diols, derived from both chiroinositol enantiomers, are used as acceptors, both the absolute configuration of the acceptor as well as the nature of the donor's and acceptor's protecting groups plays a key role in the regiochemistry of the coupling.…”