Stereocontrolled Synthesis of α-Xylofuranosides Using a Conformationally Restricted Donor

Abstract

A number of biologically relevant glycoconjugates possess 1,2-cis-furanosidic linkages, a class of glycosidic bond that remains challenging to introduce with high stereoselectivity. In this paper, we report an approach to one family of such linkages, α-xylofuranosides, via the use of thioglycoside donors possessing a conformationally restricting xylylene protecting group. The method was shown to provide the desired targets in good to excellent yield and stereoselectivity. Computational investigations support the proposal that the protecting group locks the electrophilic intermediate in these reactions into a conformation that leads to the high selectivity. The power of the methodology was demonstrated through the synthesis of a complex hexasaccharide motif from lipoarabinomannan, an immunomodulatory polysaccharide from mycobacteria.

Furanosyl Oxocarbenium Ion Conformational Energy Landscape Maps as a Tool to Study the Glycosylation Stereoselectivity of 2‐Azidofuranoses, 2‐Fluorofuranoses and Methyl Furanosyl Uronates

“…For these ions it appears that the “two‐conformer model” falls short in providing an adequate explanation to account for the (lack of) stereoselectivity and that more oxocarbenium ion conformations have to be taken into account as product‐forming intermediates. Further insight into the structure of glycosyl oxocarbenium ions and the trajectories of nucleophiles that attack these will lead to a better understanding of the S N 1 side of the glycosylation reaction mechanism continuum and this can eventually pave the way to a new stereoselective glycosylation methodology …”

“…Further insighti nto the structure of glycosylo xocarbenium ions and the trajectories of nucleophiles that attack these will lead to ab etter understanding of the S N 1s ide of the glycosylationr eactionm echanism continuum and this can eventually pave the way to a new stereoselective glycosylation methodology. [57]…”

Lipoarabinomannan as a Point-of-Care Assay for Diagnosis of Tuberculosis: How Far Are We to Use It?

“…This is in part because both extraction and purification processes are unspecific (Rahlwes et al, 2019). Recent studies have demonstrated that glycoconjugate synthesis could be an alternative method to study the structural and physical characteristics of LAM (Zhang et al, 2018;Chang et al, 2019). In this context, the generation of synthetic molecules makes the study of LAM as an Mtb virulence factor more accessible (Gao et al, 2014).…”

Total Synthesis of a Partial Structure from Arabinogalactan and Its Application for Allergy Prevention

“…[24] The cis ‐glycosidic linkage in the first galactose‐connected arabinose required the use of non‐participating O ‐protection, while the latter arabinose has a trans ‐glycosidic linkage and, therefore, requires participating O ‐protection for synthesis [25] . According to a report by Lowary and co‐workers, the cis ‐glycosylation is possible when a conformationally restricted O ‐xylylene‐protected donor is used [26, 27] . We adapted this approach and started the synthesis from l ‐arabinose ( 10 ) in a Fischer glycosylation in methanol, the product of which was subsequently benzoylated.…”

“…[25] According to ar eport by Lowary and co-workers, the cis-glycosylationi sp ossible when ac onformationally restricted O-xylylene-protected donor is used. [26,27] We adapted Figure 1. Illustration of partial structures of AG identified by Brecker and coworkers using symbol nomenclature for glycans (A).…”