Sialic acid C-glycosides with aromatic residues: Investigating enzyme binding and inhibition of Trypanosoma cruzi trans-sialidase

Sebastian Meinke, Andreas Schroven, Joachim Thiem
2011 Organic and biomolecular chemistry  
Commercially available starting materials were used without further purification. Solvents were dried according to standard methods. TLC was performed on precoated aluminium plates (Silica Gel 60 F254, Merck 5554) employing UV-absorption and charring with 10% H 2 SO 4 in ethanol for visualisation. For column chromatography Silica Gel 60, 230-400 mesh, 40-63 µm (Merck) was used. 1 H NMR and 13 C NMR spectra were recorded on Bruker AMX-400 (400.25 MHz for 1 H, 100.65 MHz for 13 C), Bruker AV-400
more » ... 400.25 MHz for 1 H, 100.65 MHz for 13 C) and on Bruker DRX-500 (500.13 MHz for 1 H, 125.77 MHz for 13 C) at 300 K. Chemical shifts were calibrated to solvent residual peaks. [26] The signals were assigned by HH-COSY, HSQC, HMBC and if necessary NOESY experiments. J values are given in Hz. Optical rotations were measured using a Perkin Elmer 241 (546 nm) or a Krüss Optronic P8000 (589 nm) at 20 °C; [α] D values are given in 10 -1 deg cm 2 g -1 . Mass spectra were recorded on a Bruker Biflex III in positive reflector mode (MALDI-TOF), on a VG Analytical VG/70-250 F (FAB) and on a Thermo Finnigan MAT 95 XL mass spectrometer (ESI). Allyl C-sialosides 3, 6, 8 [10] and substituted styrenes 4b and 4c [12] were synthesised as described and the data were consistent with those published. The syntheses of C-sialosides 5a, 10, 11 and 33 were published before in a short communication. [11] General procedure for cross metathesis with styrenes (GP1): The allyl C-sialoside was dissolved under nitrogen in anhydrous dichloromethane to yield a 0.002 M solution and the styrene (8-10-fold excess) was added. After addition of the ruthenium catalyst, the reaction was stirred under reflux for 24 h. The removal of the solvent in vacuo and column chromatography on silica gel (toluene-acetone or pure ethyl acetate) yielded the product. General procedure for acetylation (GP2): The compound was dissolved in pyridine and an excess of acetic anhydride was added. The solution was stirred at room temperature until TLC indicated complete consumption of starting material. The solvent was removed in vacuo and the residue was coevaporated with toluene before column chromatography (silica gel, toluene/acetone or pure ethyl acetate).
doi:10.1039/c0ob01176b pmid:21528140 fatcat:52wnrxkunnhbfnunc5qudjck7a