Thio-sugar motif of functional CARB-pharmacophore for antineoplastic activity. Part 2

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

“…[104,107,[111][112][113][114] Moreover, promising anti-cancer activities were also described for some of them. [28][29][30] In 1995, Witczak described the synthesis of two α(1!4) thiodisaccharides via Michael addition, one of them bearing a GlcNAc moiety. Particularly, the authors synthesised α-S-Fuc (1!4)-3-deoxy-Glc 220 and α-S-Fuc(1!4)-3-deoxy-GlcNAc 221 from αFucSH 215 and levoglucosenone 216 (Scheme 41).…”

“…[24,25] In this respect, it is noteworthy that it has been described the synthesis of a variety of thiodisaccharides having cytotoxic activity against different human cancer cell lines, reason why they have been proposed as anti-cancer drugs. [27][28][29][30] Our research is focused on glycomimetics, particularly thiodisaccharides, bearing N-acetylhexosamine (HexNAc) residues (mainly N-acetylglucosamine, GlcNAc and N-acetylgalactosamine, GalNAc), as these are fundamental monosaccharides, which are constituent of a wide range of glycans, involved in numerous biological processes. [31] These sugars are part of the N-and O-glycosidic chains of glycoproteins and so, they play important roles in intracellular signalling, cell-cell and cell-pathogen interactions.…”

Design and synthesis of glycomimetics: Recent advances

“…In a recent screening of various classes of sugars (thio‐, anhydro‐, and sulfamido‐sugars and myo‐inositol oxide), synthesized and studied for cytotoxicity against human cancer cell lines, some sulfur‐containing compounds were found to be promising for future developments due to antineoplastic activity . In particular, compound 87 to 90 (Figure ) were assessed for cytotoxicity and apoptosis against human cancer cell lines (A549, LoVo, MCF‐7, and HeLa) . Compound 87 was more active against MCF‐7 cells (an estrogen‐dependent breast cancer line), while the other thiodisaccharides showed strongest activity against A549 cells (a lung adenocarcinoma line).…”

Synthesis and Evaluation of Oligomeric Thioether-Linked Carbacyclic β-(1→3)-Glucan Mimetics

“…The reaction was quenched by adding MeOH and the mixture was concentrated under reduced pressure. Chromatographic purification (14% acetone/hexanes) afforded the title compound as a colorless oil (32, 11.8 47,72.5,72.21,72.19,66.6,55.2 (2 Cs),55.1,41.9,41.7,41.2,40.9,40.7,40.6 (2 Cs),38.6,38.5,37.8,37.0,36.92,36.85,36.3,36.2,35.5,32.2,24.0,15. 1R,3R,5R)-3-(((1S,3R,5R)-3-(((1S,3R,5S) To a stirred solution of 32 (10.5 mg, 0.02 mmol) in pyridine (0.25 mL) at room temperature was added methanesulfonyl chloride (6.7 μL, 0.09 mmol). The reaction mixture was stirred at the same temperature for 11 h before it was diluted with ethyl acetate, washed with 1 N HCl and brine, dried over Na 2 SO 4 , and concentrated under reduced pressure.…”

“…42 We found both 6 and 7 to display significant affinity for Dectin-1 and CR3, and hypothesized that this arises from the enhanced hydrophobicity of the α-face arising from removal of the C2-hydroxyl group, and replacement of the ring oxygen by a methylene group. Building on this hypothesis, and informed by the previous development of the monothioglucoside analogs 3-5 by the Ferrières laboratory, 33 and by the frequently observed enhancement of protein-small molecule and protein-carbohydrate interactions on replacement of ether units by thioethers, [43][44][45][46][47][48][49][50][51][52] we designed and prepared the di-, tri-and tetrameric 1,5-dithia analogs 8-10 ( Fig 3), and were again rewarded by the observation of significant affinity for Dectin-1 and CR3, particularly for the trimer 9. 53 Pursuing this line of investigation further, and noting the extensive history of carbacyclic motifs as carbohydrate analogs, [54][55][56][57][58][59] we now report the synthesis and evaluation of the thioether-linked carbasugar glucan mimetics 11-13 that incorporate features of the hydroxylamines 6 and 7, the dithiaglucans 8-10, and the 4-deoxyglucopyranose moiety in 2.…”