Synthesis of CH₂-linked α-galactosylceramide and its glucose analogues through glycosyl radical-mediated direct C-glycosylation

Abstract

Direct C-glycosylation of a conformationally constrained and stable C1-sp3 hybridized carbohydrate donor with a carefully designed sphingosine unit afforded the CH2-linked analogue of antitumor-active KRN7000 and its glucose congener.

Synthesis of C-acyl furanosides via the cross-coupling of glycosyl esters with carboxylic acids

“…C -Acyl glycosides are versatile synthetic intermediates to natural products, nucleoside analogues, and pharmaceutical molecules ( Scheme 1A ). 1 Downstream derivatives of C -acyl glycosides, including C -alkyl glycosides, 2 diazo derivatives, 3 alcohols, 4 nucleoside analogues, 5 and cyclopentitols, 6 display significant potentials in drug discovery and utilities in chemical biology and biochemistry studies. A C -glycoside linkage confers in vivo stability towards hydrolysis and enzymatic degradation.…”

Chemical Biology of αGalCer: A Chemist's Toolbox for the Stimulation of Invariant Natural Killer T (iNKT) Cells

“…[134] The synthetic efforts for accessing C-analogs of KRN7000 have been previously reviewed [20,135] and are briefly summarized in Figure 5B, including the most recent radical approach by Hirai and co-workers. [136] Figure 5C instead depicts synthetic precursor 46 developed by Guillaume et al [134] for the synthesis of C-6'' modified α-C-GalCer analogs 44 and 45. In the search for novel analogs with substitutions at the glycosidic linkage, the S-linked analog of αGalCer, α-S-KRN7000, was first synthesized by Dere et al [137] (Figure 6).…”

β-Glycosyl Trifluoroborates as Precursors for Direct α-C-Glycosylation: Synthesis of 2-Deoxy-α-C-glycosides

“…Therefore, the Suzuki–Miyaura coupling reaction was employed to construct C-arylated (or vinylated) glucal derivatives 2 from C1-sp 2 pinacol boronate 6 (Figure B). − This provides access to 2-deoxy-β- C -glucosides . As for C1-sp 3 glycosyl boronates, surprisingly, simple C-1 borylated monosaccharides have not been reported, except for C-1 alkylated and B-substituted monosaccharides prepared by the B–C bond insertion reaction of a glycosyl diazirine. , We envisioned that potassium β-glycosyltrifluoroborates such as 7 , which are obtainable by hydrogenation of sp 2 -boronate such as 6 (Figure C), would undergo a Ni-catalyzed metallaphotoredox coupling reaction with aryl or vinyl halides. − Single-electron oxidation of 7 would generate glycosyl radical 8 , which is expected to adopt a standard chair conformation with α-radical orientation stabilized by the inner cyclic oxygen atom. − Then, stereoinvertive coupling should proceed to give 5α selectively (Figure S1). , This approach would be complementary to the method via compound 2 and might be useful to synthesize analogues of native 2-deoxy glycosides (usually β- O -glycosides).…”