Synthesis of S-Linked Glycoconjugates and S-Disaccharides by Thiol–Ene Coupling Reaction of Enoses

Abstract

Free-radical hydrothiolation of the endocyclic double bond of enoses is reported. Reaction between 2-acetoxy-D-glucal and a range of thiols including amino acid, peptide, glycosyl thiols, and sugars with primary or secondary thiol functions gave S-linked α-glucoconjugates and S-disaccharides with full regio- and stereoselectivity. Addition of glycosyl thiols to a 2,3-unsaturated glycoside also proceeded with good selectivity and afforded a series of 3-deoxy-S-disaccharides.

Systematic study on free radical hydrothiolation of unsaturated monosaccharide derivatives with exo- and endocyclic double bonds

“…17 Thus, the reactions were carried out in toluene at room temperature with a 2 : 1 thiol : ene ratio by irradiation at λ max 365 nm for 3 × 15 min in the presence of 2,2-dimethoxy-2-phenylacetophenone (DPAP) (3 × 0.1 equiv.) as the cleavable photoinitiator 1a (Table 1).…”

“…In those cases, significantly enhanced yields could be reached by changing the tolueneMeOH systems to DMF-water. 17 Here, we decided to study how the solvent affects the reaction when low conversion was observed in toluene. Thus, the reaction of 2-acetoxy glycal 1 and thiol 2c was carried out in different solvents with a thiolene ratio of 2 : 1, irradiating at λ max 365 nm for 3 × 15 min (Table 2).…”

“…16 The incorporation of 2-acetoxy-glycals and 2,3-unsaturated glycosides within the thiol-ene coupling strategy was reported for the first time by our group. 17 We have shown that reactions between 2-acetoxy-D-glucal and a range of thiols including amino acid, peptide, and sugar thiols gave 1,2-cis-α-S-glucoconjugates and S-disaccharides with full regio-and stereoselectivities in good to excellent yields. Addition of 1-thioglycoses to a 2,3-unsaturated glycoside (Ferrier glycal) was found to proceed also with high selectivity offering easy access to 3-deoxy-S-disaccharides.…”

“…14 The carbohydrate skeleton itself with an exo-or endocyclic double bond has scarcely been applied as the ene partner, with only three articles published until now. [15][16][17] Dondoni and co-workers were the first to exploit the thiol-ene reaction for the synthesis of S-disaccharides by reacting sugar thiols with exo-and endoglycals. 15,16 They found that hydrothiolation of the exocyclic double bond of hex-5-enopyranoside and pent-4-enofuranoside derivatives with 1-thioglycoses afforded S-disaccharides with high yields and diastereoselectivites of up to 99%.…”

“…Addition of 1-thioglycoses to a 2,3-unsaturated glycoside (Ferrier glycal) was found to proceed also with high selectivity offering easy access to 3-deoxy-S-disaccharides. 17 Regarding the great potential of hydrothiolation of the easily available glycals in the synthesis of thioglycosides, which are especially valuable glycoside mimics, further exploration and exploitation of the reaction can be foreseen. Here we present a systematic study of the reactivity of the acetylated and benzylated derivatives of 2-hydroxy-D-glucal towards a range of thiols in the photoinduced thiol-ene coupling reaction, in comparison to the reactivity of saccharides bearing an exomethylene moiety.…”