Synthesis of Thiodisaccharides Bearing N‐Acetylhexosamine Residues: Challenges, Achievements and Perspectives

Abstract

Carbohydrate-protein interactions are involved in a myriad of biological processes. Thus, glycomimetics have arisen as one of the most promising synthetic targets to that end. Within the broad variety of glycomimetics, thiodisaccharides have proven to be excellent tools to study these processes, and even more, some of them unveiled interesting biological activities. This review brings together research made on the introduction of N-acetylhexosamine residues into thiodisaccharides to date, passing through classic substitution (as S N 2, thioglycosylation and ring-opening reactions) and addition (as thiol-ene coupling and Michael-type additions) reactions. Recent and interesting developments regarding addition reactions to vinyl azides, cross-coupling reactions and novel chemoenzymatic methods are also discussed.

Synthesis of Oligosaccharides Containing the S-Galp(α1 → 3)Galp Unit, Glycomimetic of the Epitope Recognized by Lytic Antibodies

“…Interestingly, the reaction did not occur in DMF but proceeded well when HMPA was used as the solvent. The addition of 15-crown ether did not produce any improvement as reported for other substrates . Thus, several conditions were evaluated in order to minimize the use of additives and HMPA, and a DMF:HMPA ratio of 6:1 was found to be most convenient (Table ).…”

“…6 Hz, H-4), 4.00 (1H, dd, J 4′,5′ 1.1 Hz, J 4′,3′ 3.6 Hz, H-4′), 3.78−3.70 (6H, m, H-6′a, H-6a, H-6b, OCH 3 ), 3.62 (1H, dd, J 6′b,5′ 1.9 Hz, J 6′b,6′a 12.2 Hz, H-6′b), 3.50 (1H, dd, H-3′), 3.39 (1H, ddd, J 5,6a 2.2 Hz, J 5,6b 3.7 Hz, H-5), 2.91 (1H, s.a., H-5′), 0.89 (9H, s, SiC(CH 3 ) 3 ), 0.04, −0.02 (6H, s, SiCH 3 × 2). 13 (26). To a solution of 25 (0.55 g, 0.52 mmol) in anhydrous THF (10 mL), TBAF (0.23 g, 0.87 mmol) and AcOH (76 μL, 1.33 mmol) were added, and the solution was stirred for 2 h at room temperature.…”

“…The synthesis of S -glycosides and their application in many biological systems have been review. − The most popular method to produce thiodisaccharides involves a classical S N 2 reaction where a nucleophilic 1-thio-glycopyranose displaces a good leaving group. It should be noted that the β-anomer of the 1-thio- S -galactopyranose precursor, needed to construct a β-thioglycosidic bond, is readily obtained from peracetyl galactopyranose by standard methods. , The α-anomer can be obtained from the β-anomer through an additional step of anomerization …”

Synthesis of thiodisaccharides related to 4-thiolactose. Specific structural modifications increase the inhibitory activity against E. coli β-galactosidase

“…[22][23][24][25][26] Therefore, the synthesis of thiooligosaccharides, and specifically thiodisaccharides, has attracted great attention and novel highly diastereoselective and efficient synthetic procedures have been developed. 27,28 In our laboratory, we have designed and carried out various strategies for the synthesis of thiodisaccharides, ranging from Michael conjugate addition [29][30][31][32][33] to three-membered ring-opening reactions (epoxides 34,35 or thiiranes 35,36 ) and even substitution reactions. 37 In most cases, the target enzyme to be inhibited was β-galactosidase from E. coli.…”

The disulfide bond as a key motif for the construction of multivalent glycoclusters

“…1–5 In this sense, the replacement of the interglycosidic oxygen by a sulfur atom has been extensively employed to obtain hydrolytically stable derivatives in biological media. 6,7 Thus, a variety of thioglycosides and thiodisaccharides have been synthesized and evaluated as ligands and inhibitors of carbohydrate-binding proteins as lectins, glycosidases and glycosyltransferases. 1,8,9 Moreover, their covalent attachment to multivalent scaffolds led to a complex family of glycomimetic-exposing multivalent ligands, showing in most cases, enhanced affinity to the corresponding target lectins.…”