Synthesis of a tetrasaccharide repeating unit of O-antigenic polysaccharide of Salmonella enteritidis by use of unique and odorless dodecyl thioglycosyl donors

Abstract

General Procedures: All chemicals were purchased as reagent grade and used without further purification whereas N-iodosuccinimide (NIS) was recrystallized by 1,4-dioxane and diethyl ether (1:1, v/v) before use. Dichloromethane (CH 2 Cl 2 ) and 1,2-dichloroethane were distilled over calcium hydride (CaH 2 ). Molecular sieves (MS) used for glycosylation were 4Å, which were activated at 200 ˚C under reduced pressure prior to use. Reactions were monitored by thin-layer chromatography (TLC) on a pre-coated plate of silica gel 60F 254 (layer thickness, 0.25 mm; E. Merck, Germany). Spots were detected under UV (254 nm) and/or by spraying with p-methoxybenzaldehyde-H 2 SO 4 -MeOH (1:2:17, v/v/v) and heated for a few minutes. Silica gel 60 with 0.043-0.2 mm (E. Merck, Germany) was used for open column chromatography.Size exclusion column chromatography was performed on Sephadex G-15 (Pharmacia Biotech AB, Uppsala, Sweden) and deionized water as the eluent.1 H and 13 C NMR spectra were recorded with a Bruker ASX 300 (300 and 75.1 MHz, respectively) and JEOL ECA 600 (600 and 125 MHz). Chemical shifts (in ppm) were referenced to tetramethylsilane (δ = 0 ppm) in deuterated chloroform (CDCl 3 ). Coupling constant are given in Hertz. 13 C NMR spectra were obtained by using the same NMR spectrometers and were calibrated with CDCl 3 (δ = 77.00 ppm). Splitting patterns are indicated as s, singlet; d, doublet; t, triplet; q, quartet; m, multiplet; brd, broad doublet for 1 H NMR data. ESI-HR mass spectra were measured on a JEOL JMS-T100LCP and FAB-HR mass was carried out using a JEOL JMS-HX100.

Reversal of Anomeric Selectivity with O‐Glycosyl Trichloroacetimidates as Glycosyl Donors and Thiols as Acceptors Under Acid/Base Catalysis

“…Other acceptors, such as propanethiol ( B ), dodecanethiol ( C ), cyclohexanethiol ( D ) and methyl 2,3,4‐tri‐ O ‐benzyl‐6‐deoxy‐6‐mercapto‐α‐ D ‐glucopyranoside ( E ),11 showed similar strong preferences for the β anomers 1B β ,12 1C β ,13 1D β 14 and 1E β , respectively (entries 9–12). Also, other glycosyl donors, such as lactosyl trichloroacetimidate 2 α ,6 2‐azido‐α‐ D ‐glucopyranosyl trichloroacetimidate 3 α 15 and α‐ D ‐galactosyl trichloroacetimidate 4 α ,16 gave under the standard reaction conditions mainly β products ( 2A β – 2C β , 3A β – 3C β , 4A β , 4B β ,10 4C β 17 and 4E β ; entries 13–22). Hence, the envisaged reversal of anomeric selectivity in comparison with the more common glycosidation procedures (entries 1 and 3) was confirmed, thus strongly supporting the initial formation of an adduct between PhBF 2 and the thiol group and subsequent S N 2‐type reaction with the glycosyl donor.…”

Synthetic Glycans to Improve Current Glycoconjugate Vaccines and Fight Antimicrobial Resistance

“…Both structures present a rare tyvelose monosaccharide which was shown to play an important role in pathogenesis . The first synthesis of the α- d -Gal-(1–2)-[α- d -Tyv-(1–3)]-α- d -Man-(1–4)-α- l -Rha tetrasaccharide repeating unit was achieved by using a key dodecylthioglycosyl donor . Recently, Huang’s group reported the synthesis of the tetrasaccharide frameshift α- d -Tyv-(1–3)-α- d -Man-(1–4)-α- l -Rhap-(1–3)-α- d -Gal ( 107 ) following a [2+2] glycosylation strategy.…”

“…339 The first synthesis of the α-D-Gal-(1−2)-[α-D-Tyv-(1−3)]-α-D-Man-(1−4)-α-L-Rha tetrasaccharide repeating unit was achieved by using a key dodecylthioglycosyl donor. 340 Recently, Huang's group reported the synthesis of the tetrasaccharide frameshift α-D-Tyv-(1−3)-α-D-Man-(1−4)-α-L-Rhap-(1−3)-α-D-Gal (107) following a [2+2] glycosylation strategy. The tetrasaccharide conjugated to Qβ (108) proved to be immunogenic in mice and rabbits, suggesting that one repeating unit is sufficient to produce anti-OPS antibodies.…”

Synthesis of and molecular dynamics simulations on a tetrasaccharide corresponding to the repeating unit of the capsular polysaccharide from Salmonella enteritidis

“…9 After we had completed the synthesis and during the analysis of the molecular dynamics (MD) simulations, a different synthesis of the same tetrasaccharide appeared. 10 NIS-promoted glycosylation at -30 • C with methyl 2,3-Oisopropylidene-a-L-rhamnopyranoside (3) 12 gave the desired disaccharide 4 in 92% yield. Debenzoylation, followed by a second NIS-promoted a-glycosylation with ethyl 2,3,4,6-tetra-O-benzyl-1-thio-b-D-galactopyranoside (6) 13 as donor in diethyl ether at -30 • C, gave protected trisaccharide 7 exclusively, in 85% yield.…”