A Click Ligation Based on SuFEx for the Metal‐Free Synthesis of Sugar and Iminosugar Clusters

Abstract

Although the preparation of anomeric glycosylsulfonyl fluoride was unsuccessful, a tetra‐O‐acetylated C‐glucosylpropanesulfonyl fluoride was synthesized starting from the corresponding thioacetate via sulfonate formation as the key intermediate. This sulfonyl fluoride was a bench‐stable product that reacted promptly with primary and secondary alkylamines at 80 °C to give the corresponding sulfonamides in good yield. On the other hand, the same fluoride was inert toward arylamines whereas its precursor, the sulfonyl chloride, showed good reactivity. Another limitation of the acetylated sugar sulfonyl fluoride was its lack of reactivity with a multivalent aminated calixarene, this being due to acetyl transfer from the carbohydrate moiety to the amino groups of the scaffold. Fortunately, the tetra‐O‐benzylated C‐glucosylpropanesulfonyl fluoride, prepared by the same reaction sequence employed for the synthesis of the acetylated analogue, reacted with the tetra‐aminopropyl‐calix[4]arene to afford the corresponding sulfonamide‐linked sugar cluster in high isolated yield. A similar approach to the synthesis of calixarene‐based iminosugar clusters was unsuccessful because 1‐deoxynojirimycin sulfonyl fluoride derivatives could not be generated. However, a tetra‐propylsulfonyl fluoride calixarene, obtained from the free‐OH calix[4]arene through a three‐step reaction sequence, underwent clean coupling with both C‐glucosylpropylamine and N‐aminopentyl‐1‐deoxy‐deoxynojirimycin derivatives to give the corresponding tetravalent sugar and iminosugar clusters. This metal‐free click reaction may constitute a valuable tool in the arsenal of ligation tools for the synthesis of multivalent carbohydrate architectures.

SuFEx-enabled, agnostic discovery of covalent inhibitors of human neutrophil elastase

“…click chemistry | SuFEx | agnostic | covalent inhibitor | elastase S ulfur fluoride exchange (SuFEx)-the new-generation click chemistry, since first introduced in 2014 (1), has quickly found diverse applications across an array of fields (DOI: 10.1039/C8CS00960K), including chemical synthesis (2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12), material science (13)(14)(15)(16)(17)(18)(19), chemical biology (20)(21)(22)(23)(24)(25)(26)(27)(28)(29)(30)(31)(32), and drug discovery (33,34). SuFEx creates robust intermolecular links between modules.…”

A Broad-Spectrum, Catalytic Amidation of Sulfonyl Fluorides and Fluorosulfates

“…Flash column chromatography was performed on 200-300 mesh silica gel (Huanghai, China). 2-(diphenylphosphanyl)-5-methylbenzenesulfonyl fluoride (1a), [1] 4-methylbenzenesulfonyl fluoride (1c), [2] 4-methoxybenzenesulfonyl fluoride (1e), [2] 2-methylbenzenesulfonyl fluoride (1f), [3] 4-(trifluoromethyl)benzenesulfonyl fluoride (1g), [3] 4-fluorobenzenesulfonyl fluoride (1h), [4] benzenesulfonyl fluoride (1i), [4] 4-(tert-butyl)benzenesulfonyl fluoride (1l), [2] naphthalene-1-sulfonyl fluoride (1m), [2] ((1S,4R)-7,7-dimethyl-2-oxobicyclo[2.2.1]heptan-1-yl)methanesulfonyl fluoride (1n), [2] 4-methoxyphenyl fluorosulfate (4b), [5] 4-isopropylphenyl fluorosulfate (4d), [6] 4-iodophenyl fluorosulfate (4e), [7] 3,5-dimethylphenyl fluorosulfate (4f), [8] benzo [d] [1,3]dioxol-5-yl fluorosulfate (4g), [3] phenyl fluorosulfate (4h), [5] phenyl fluorosulfate, [3] 4-bromophenyl fluorosulfate (4i), [9] [1,1'biphenyl]-4-yl fluorosulfate (4j), [3] (8R,9S,13S,14S)-13-methyl-17-oxo- 7,8,9,11,12,13,14,15,16,17-decahydro-6H-cyclopenta[a]phenanthren-3-yl fluorosulfate (4n), [10] (8R,9S,13S,14S,17R)-17-ethynyl-17-hydroxy-13-methyl- 7,8,9,11,12,13,14,15,16,17-decahydro-6H-cyclopenta[a]phenanthren-3-yl fluorosulfate (4o), [3] 3-nitrobenzenesulfonyl fluoride (8), [3] 4-(2-(pyrrolidin-1-yl)ethoxy)aniline (12), [11] 1H-benzo [d] [1,2,3]triazol-1-yl benzenesulfonate (16),…”

“…1 [16] 10.0 equiv none DMF (0.1 M) 80 C 2 [16] 10.0 equiv 20.0 equiv TEA DMF (0.1 M) 80 C 3 [3] 1.1 equiv 2.5 equiv MgO CH3CN/H2O = 1:1 (0.5 M) 80 C 4 [17] 1.1 equiv 2.5 equiv Cs2CO3 CH3CN (0.3 M) 25 C 5 [18] 3.0 equiv none DCM (0.4 M) 25 C 6 [19] 1.0 equiv 1.0 equiv DMAP DMSO (0.2 M) 80 C 7 [20] 2.0 equiv 1.0 equiv Ca(NTf2)2 t-amylOH (0.2 M) 60 C 8 [21] 2.0 equiv 0.3 equiv DBU Neat 25 C 9 [21] 2.0 equiv 0.3 equiv DBU THF (0.02 M) 25 C 10 1.0 equiv 1.0 equiv DBU DMSO (0.2 M) 80 C 11 1.0 equiv 1.0 equiv DBU DMF (0.2 M) 80 C…”

Glycosyl disulfides: importance, synthesis and application to chemical and biological systems

“…Synthesis of symmetrical glycosyl disulfides is typically achieved by oxidation of the corresponding glycosyl thiol with iodine, [12][13][14][15] hydrogen peroxide, [15][16][17] diethylazodicarboxylate…”