Conformational properties of glucosyl-thioglucosides and their S-oxides in solution

A stereochemical study of a series of alkyl glucosyl-β-(1→6)-thioglucosides and their S-oxides by means of nuclear magnetic resonance and circular dichroism revealed that the populations around the thioglucosidic bond (ring I) as well as those of the interglycosidic linkage ω depend on the aglycone, the solvent and, in the S-oxides, on the absolute configuration of the sulfur atom. The results for the thio-disaccharides showed the strong influence of the solvent polarity on the conformational preferences of the interglycosidic bond. In polar solvents, the magnitudes of the rotamer populations, Pgg and Pgt, remained practically constant through the series, while in non-polar solvents a clear predominance of gt conformation was observed as well as the influence of the aglycone on the conformational equilibrium. The results for both (SS)- and (RS)-alkyl thiogentiobiosyl S-oxide series showed a clear predominance of the gt rotamer, Pgt always having a higher magnitude in the latter series than in the former. Both series exhibited linear correlations between interglycosidic Pgg and Pgt and Taft’s steric parameter (ES) for the alkyl group attached to the sulfinyl group, especially in non-polar solvents. The stereochemical study around the C1–S bond established that the flexibility around this linkage depends on aglycone size, solvent polarity, and the absolute configuration of the sulfur, derivatives of the SS series showing higher flexibility in both polar and non-polar media. The conformational properties of these compounds in solution are explained in terms of stereoelectronic, steric, and solvent effects.

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Methyl 2,3,4-tri-O-acetyl-6-O-(2,3,4,6-tetra-O-acetyl-β-d-glucopyranosyl)-1-thio-β-d-glucopyranosideC27H38O17S[α]D = −7.9 (c 0.6, CHCl3)Source of chirality: β-Gentiobiose

Ethyl 2,3,4-tri-O-acetyl-6-O-(2,3,4,6-tetra-O-acetyl-β-d-glucopyranosyl)-1-thio-β-d-glucopyranosideC27H40O17S[α]D = −20.0 (c 0.6, CHCl3)Source of chirality: β-Gentiobiose

iso-Propyl l 2,3,4-tri-O-acetyl-6-O-(2,3,4,6-tetra-O-acetyl-d-glucopyranosyl)-1-thio-β-d-glucopyranosideC29H42O17S[α]D = −20.5 (c 0.4, CHCl3)Source of chirality: β-Gentiobiose

Cyclohexyl 2,3,4-tri-O-acetyl-6-O-(2,3,4,6-tetra-O-acetyl-β-d-glucopyranosyl)-1-thio-β-d-glucopyranosideC32H46O17S[α]D = −21.4 (c 0.6, CHCl3)Source of chirality: β-Gentiobiose

tert-Butyl 2,3,4-tri-O-acetyl-6-O-(2,3,4,6-tetra-O-acetyl-β-d-glucopyranosyl)-1-thio-β-d-glucopyranosideC30H44O17S[α]D = −12.8 (c 0.5, CHCl3)Source of chirality: β-Gentiobiose

(SS)-Methyl 2,3,4-tri-O-acetyl-6-O-(2,3,4,6-tetra-O-acetyl-β-d-glucopyranosyl)-1-thio-β-d-gluco-pyranoside S-oxideC27H38O18S[α]D = -7.1 (c 0.3, CHCl3)CD (CH3CN) λext (Δɛ): 223 (+4.4), 200 (−11.9)Source of chirality: β-Gentiobiose

(RS)-Methyl 2,3,4-tri-O-acetyl-6-O-(2,3,4,6-tetra-O-acetyl-β-d-glucopyranosyl)-1-thio-β-d-gluco-pyranoside S-oxideC27H38O18S[α]D = −50.8 (c 0.4, CHCl3)CD (CH3CN) λext (Δɛ): 218 (−8.6), 194 (+4.4)Source of chirality: β-Gentiobiose

(SS)-Ethyl 2,3,4-tri-O-acetyl-6-O-(2,3,4,6-tetra-O-acetyl-β-d-glucopyranosyl)-1-thio-β-d-gluco-pyranoside S-oxideC28H40O18S[α]D = −25.0 (c 0.7, CHCl3)CD (CH3CN) λext (Δɛ): 227 (+8.4), 201 (−17.9)Source of chirality: β-Gentiobiose

(RS)-Ethyl 2,3,4-tri-O-acetyl-6-O-(2,3,4,6-tetra-O-acetyl-β-d-glucopyranosyl)-1-thio-β-d-gluco-pyranoside S-oxideC28H40O18S[α]D = −46.1 (c 0.2, CHCl3)CD (CH3CN) λext (Δɛ): 220 (−10.8), 196 (+3.2)Source of chirality: β-Gentiobiose

(SS)-Isopropyl 2,3,4-tri-O-acetyl-6-O-(2,3,4,6-tetra-O-acetyl-β-d-glucopyranosyl)-1-thio-β-d-gluco-pyranoside S-oxideC29H42O18S[α]D = −1.7 (c 1.1, CHCl3)CD (CH3CN) λext (Δɛ): 229 (+7.6), 203 (−6.4)Source of chirality: β-Gentiobiose

(RS)-Isopropyl 2,3,4-tri-O-acetyl-6-O-(2,3,4,6-tetra-O-acetyl-β-d-glucopyranosyl)-1-thio-β-d-gluco-pyranoside S-oxideC29H42O18S[α]D = −50.0 (c 0.5, CHCl3)CD (CH3CN) λext (Δɛ): 222 (−9.4), 198 (+2.9)Source of chirality: β-Gentiobiose

(SS)-tert-Butyl 2,3,4-tri-O-acetyl-6-O-(2,3,4,6-tetra-O-acetyl-β-d-glucopyranosyl)-1-thio-β-d-gluco-pyranoside S-oxideC30H44O18S[α]D = +8.3 (c 0.6, CHCl3)CD (CH3CN) λext (Δɛ): 230 (+7.9), 203 (−6.8)Source of chirality: β-Gentiobiose

(RS)-tert-Butyl 2,3,4-tri-O-acetyl-6-O-(2,3,4,6-tetra-O-acetyl-β-d-glucopyranosyl)-1-thio-β-d-gluco-pyranoside S-oxideC30H44O18S[α]D = −51.1 (c 0.4, CHCl3)CD (CH3CN) λext (Δɛ): 224 (−8.2), 204.5 (+8.4)Source of chirality: β-Gentiobiose