Synthesis of Branched Dithiotrisaccharides via Ring-Opening Reaction of Sugar Thiiranes

Abstract

Satisfactory procedures are described for the synthesis of 5,6- and 3,4-thiirane derivatives from the respective hexofuranose or hexopyranose epoxide precursors. The controlled ring-opening reaction of thiiranes by 1-thioaldoses was successfully accomplished to afford, regio- and stereoselectively, β-S-(1→4)-3,4-dithiodisaccharides. For instance, the regioselective attack of per-O-acetyl-1-thioglucose (16) to C-4 of 2-propyl 2,6-di-O-acetyl-3,4-epithio-α-D-galactopyranoside (14) gave the derivative of Glcp-β-S-(1→4)-3,4-dithioGlcp-O-iPr (17). This thiodisaccharide was accompanied by the (1→3)-disulfide 18, formed between 16 and 17, and the symmetric (3→3)-disulfide 19, which resulted from the oxidative dimerization of 17. However, the S-acetyl derivative of 17 could be obtained in good yield (62%) by LiAlH(4) reduction of the crude mixture 17-19, followed by acetylation. The same sequence of reactions starting from 14 and the 1-thiolate of Galp afforded the per-O,S-acetyl derivative of Galp-β-S-(1→4)-3,4-dithio-α-D-Glcp-O-iPr (23), which was selectively S-deacetylated to give 25. The dithiosaccharides 17 and 25 are 3,4-di-S-analogues of derivatives of the natural disaccharides cellobiose and lactose, respectively. The ring-opening reaction of 5,6-epithiohexofuranoses of D-galacto (8) or L-altro (11) configuration with 1-thioaldoses was also regio- and stereoselective to give the respective β-S-(1→6)-linked 5,6-dithiodisaccharides 26 or 29 in excellent yields. Glycosylation of the free thiol group of 17, 25, or 26, using trichloroacetimidates as glycosyl donors, led to the corresponding branched dithiotrisaccharides. Some of them are sulfur analogues of derivatives of branched trisaccharides found in natural polysaccharides.

Synthesis of Thiodisaccharide Sulfoxides and Sulfones – Determination of the Configuration of the Sulfur Stereocentre

“…[7,22] The thiodisaccharides have S-(1Ǟ3)-or S-(1Ǟ4)-linkages, and have Glcp or Galp units at the non-reducing end. [7,22] The thiodisaccharides have S-(1Ǟ3)-or S-(1Ǟ4)-linkages, and have Glcp or Galp units at the non-reducing end.…”

Photoinitiated Thiol‐ene Reactions of Enoses: A Powerful Tool for Stereoselective Synthesis of Glycomimetics with Challenging Glycosidic Linkages

“…The most common approaches for S‐glycosylation include nucleophilic displacement of the anomeric leaving group of glycosyl donors by thiol nucleophiles (Scheme A) and utilization of glycosyl thiols in various base‐promoted reactions (Scheme B, a–c) . The classical nucleophilic substitution reaction at the anomeric carbon often proceeds, at least partly, through an oxocarbenium ion, resulting in complete loss of anomeric integrity of the donor, and leading to the formation of a mixture of α‐ and β‐glycosides (Scheme A) .…”

“…The most common approaches for S-glycosylation include nucleophilic displacement of the anomeric leaving group of glycosyld onors by thiol nucleophiles (Scheme 1A) [7][8][9][10] and utilization of glycosylt hiols in various base-promoted reactions (Scheme 1B,a -c). [11][12][13][14] The classical nucleophilic substitution reactiona tt he anomeric carbon often proceeds, at least partly, through an oxocarbenium ion, resulting in complete loss of anomeric integrity of the donor,a nd leading to the formation of am ixture of a-a nd b-glycosides (Scheme1A). [7,15] The a/b-stereoselectivity in these reactions fundamentally depends on the identitya nd protecting groups of the donora nd can be affected by the steric and stereoelectronic effectsa round the anomeric center.Although 1,2-trans glycosides can be efficiently prepared by anchimeric assistance of the carbonyl-based C2 protecting groups, this method has only limited efficacy in the stereoselective synthesis of 2-deoxy glycosides and1 ,2-cis glycosides.M oreover,t he anomeric effect, which can be exploited for the axial a-O-glycosylation, is subtle for S-glycosidesa nd its impact on thes tereochemical outcome of the glycosylationi s hardly to predict, further complicating the formation of the 1,2-cis a-S-glycosidic bond.…”

Convergent strategy for the synthesis of S-linked oligoxylans

“…Firstly, sulfur atoms are incompatible with catalytic hydrogenolysis [14] , which complicates the use of benzyl ethers as protective groups, and secondly, thiols easily form disulfides, both as glycosyl donors and acceptors. [15] Using a thiol as the acceptor facilitates the utilization of most of the known O-glycosylation methods and allows for the variation of the donor to find the right "match" for the thiol acceptor. However, only glycosylation methods using promoters that are not thiophilic can be employed, which disqualifies some of the O-glycosylation methods (e.g.…”