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Journal of Chemistry
Volume 2013, Article ID 568907, 4 pages
http://dx.doi.org/10.1155/2013/568907
Research Article

Synthesis of Novel S-Glucosides Containing 5-Methylisoxazole Substituted 1,2,4-Triazole

Department of Chemistry, Xinxiang Medical University, Henan, Xinxiang 453003, China

Received 1 April 2012; Accepted 19 May 2012

Academic Editor: Lorenzo Cerretani

Copyright © 2013 Shujun Chao and Yingling Wang. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Nine new S-β-D-glucosides containing 4-aryl-5-(5-methylisoxazol-3-yl)-1,2,4-triazol-3-thiols have been synthesized by the direct glycosylation of 4-aryl-5-(5-methylisoxazol-3-yl)-1,2,4-triazol-3-thiols with 2,3,4,6-tetra-O-acetyl-α-D-glucopyranosyl bromide in ethanol in the presence of potassium hydroxide followed by deacetylation using dry ammonia in dry methanol. All the compounds synthesized have been characterized by their elemental analyses and spectral data.

1. Introduction

Much attention has been focused on 1,2,4-triazole derivatives for their broad-spectrum activities, such as antitumor [1], anticonvulsant [2], antifungal [3], herbicidal, and plant growth regulatory activities [4]. Up till now, many 1,2,4-triazole derivatives have been synthesized, and some of them have been patented for commercial uses. Similarly, 5-methylisoxazole derivatives have also shown biological effects such as antibacterial [5] and phytohormone effects [6].

Recently thioglycosides have received considerable attention, because they are widely employed as biological inhibitors, inducers, and ligands for affinity chromatography for carbohydrate processing-enzymes and proteins [7, 8]. In 1972, Witkoski et al. synthesized Ribavirin [9] and proved that it not only possesses inhibitory activity against a range of DNA and RNA viruses [10, 11] but also displays antitumor activity [12] in mice. After the recognized biological properties of Ribavirin, the synthesis and biological evaluation of N-glucosides [13] and C-glucosides [14] containing 1,2,4-triazole have been greatly emphasized, but only a few S-glucosides [15] containing 1,2,4-triazole have been reported. To the best of our knowledge, S-glucosides containing 5-methylisoxazole substituted 1,2,4-triazole have not been reported to date. In view of these observations and our interests in the synthesis of biologically active heterocyclic compounds, herein we describe the synthesis of novel S-glucosides containing 5-methylisoxazole substituted 1,2,4-triazole from 4-aryl-5-(5-methylisoxazol-3-yl)-1,2,4-triazol-3-thiols and 2,3,4,6-tetra-O-acetyl-α-D–glucopyranosyl bromide (Scheme 1).

568907.sch.001
Scheme 1: 4-Aryl-5-(5-methylisoxazol-3-yl)-1,2,4-triazol-3-thiols (1a-1i) were synthesized according to the literature [16, 17].

2. Experimental

Melting points were determined on an X-4 microscopic melting point apparatus and were uncorrected. 1H NMR spectra were determined on a Varian Mercury-300 MHz spectrometer at room temperature using TMS as internal standard, coupling constants (J) were measured in Hz. Elemental analysis were performed by Elementar Vario EL apparatus. Commercially available reagents were used throughout without further purification unless otherwise stated.

General procedure for Preparation of 3-S-(2′,3′,4′,6′-tetra-O-acetyl-β-D-glucopyranosyl)-4-aryl-5-(5-methylisoxazol-3-yl)-1,2,4-triazoles(2a~2i).

To a solution of KOH (2 mmol) in ethanol (25 mL) was added 1a-1i (2 mmol). After the mixture was stirred for 30 min at room temperature, 2,3,4,6-tetra-O-acetyl-α-D-glucopyranosyl bromide (2 mmol) was added to the solution. The reaction was stirred for an appropriate time and monitored by TLC until the final conversion. The mixture was filtered and washed with water. The crude product was purified by silica gel column chromatography using petroleum ether/ethyl acetate as eluent to afford the pure product.(2a)Yield 74%. Mp 172-173°C. 4° (c 1, CH2Cl2). 1H NMR (300 MHz, CDCl3): δ 1.96 (s, 3H, CH3C=O), 1.97 (s, 3H, CH3C=O), 1.98 (s, 3H, CH3C=O), 1.99 (s, 3H, CH3C=O), 2.42 (s, 3H, Het-CH3), 3.82 (m, 1H), 4.07 (dd, J = 12.6, 2.1 Hz, 1H), 4.21 (dd, J = 12.6, 4.2 Hz, 1H), 5.04–5.11 (m, 2H), 5.25 (t, J = 9.3 Hz, 1H), 5.57 (d, J = 10.5 Hz, 1H), 6.55 (s, 1H, HetH), 6.85–7.51 (m, 5H, ArH). Anal. Calcd. for C26H28N4O10S: C, 53.06; H, 4.79; N, 9.52. Found: C, 52.89; H, 4.67; N, 9.25.(2b)Yield 72%. Mp 152–154°C. 5° (c 1, CH2Cl2). 1H NMR (300 MHz, CDCl3): δ 1.94 (s, 3H, CH3C=O), 1.96 (s, 3H, CH3C=O), 1.97 (s, 3H, CH3C=O), 2.00 (s, 3H, CH3C=O), 2.02 (s, 3H, CH3), 2.41 (s, 3H, Het-CH3), 3.80–3.85 (m, 1H), 4.03–4.14 (m, 1H), 4.20–4.29 (m, 1H), 5.05–5.14 (m, 2H), 5.25–5.32 (m, 1H), 5.64–5.76 (m, 1H), 6.56 (s, 1H, HetH), 6.87 (d, J = 7.5 Hz, 1H, ArH), 6.99–7.46 (m, 3H, ArH). Anal. Calcd. for C27H30N4O10S: C, 53.81; H, 5.02; N, 9.30. Found: C, 53.45; H, 4.95; N, 8.92.(2c)Yield 66%. Mp 146-147°C. 3° (c 1, CH2Cl2). 1H NMR (300 MHz, CDCl3): δ 1.94 (s, 3H, CH3C=O), 1.95 (s, 3H, CH3C=O), 1.96 (s, 3H, CH3C=O), 1.97 (s, 3H, CH3C=O), 2.31 (s, 3H, CH3), 2.42 (s, 3H, Het-CH3), 3.75–3.80 (m, 1H), 4.02–4.06 (m, 1H), 4.21 (dd, J = 12.9, 4.5 Hz, 1H), 5.02–5.10 (m, 2H), 5.23 (t, J = 9.3Hz, 1H), 5.57 (d, J = 10.8 Hz, 1H), 6.54 (s, 1H, HetH), 6.86 (d, J = 7.8 Hz, 1H, ArH), 6.94–7.47 (m, 3H, ArH). Anal. Calcd. for C27H30N4O10S: C, 53.81; H, 5.02; N, 9.30. Found: C, 53.66; H, 5.12; N, 9.07.(2d)Yield 78%. Mp 88–90°C. −9° (c 1, CH2Cl2). 1H NMR (300 MHz, CDCl3): δ 1.99 (s, 3H, CH3C=O), 2.00 (s, 3H, CH3C=O), 2.01 (s, 3H, CH3C=O), 2.03 (s, 3H, CH3C=O), 2.41 (s, 3H, Het-CH3), 3.65 (s, 3H, CH3O), 3.75–3.82 (m, 1H), 4.02–4.10 (m, 1H), 4.20–4.30 (m, 1H), 5.03–5.14 (m, 2H), 5.22–5.30 (m, 1H), 5.53–5.58 (m, 1H), 6.56 (s, 1H, HetH), 6.87 (d, J = 6.9 Hz, 1H, ArH), 6.96–7.49 (m, 3H, ArH). Anal. Calcd. for C27H30N4O11S: C, 52.42; H, 4.89; N, 9.06. Found: C, 52.60; H, 4.93; N, 9.31.(2e)Yield 64%. Mp 86–88°C. −5° (c 1, CH2Cl2). 1H NMR (300 MHz, CDCl3): δ 1.99 (s, 3H, CH3C=O), 2.00 (s, 3H, CH3C=O), 2.02 (s, 3H, CH3C=O), 2.04 (s, 3H, CH3C=O), 2.41 (s, 3H, Het-CH3), 3.78–3.82 (m, 1H), 4.03–4.13 (m, 1H), 4.22–4.27 (m, 1H), 5.03–5.17 (m, 2H), 5.27 (t, J = 9.3 Hz, 1H), 5.58 (d, J = 9.9 Hz, 1H), 6.63 (s, 1H, HetH), 6.87–7.47 (m, 4H, ArH). Anal. Calcd. for C26H27BrN4O10S: C, 46.78; H, 4.08; N, 8.39. Found: C, 46.48; H, 3.97; N, 8.51.(2f)Yield 55%. Mp 98–100°C. 3° (c 1, CH2Cl2). 1H NMR (300 MHz, CDCl3): δ 2.00 (s, 3H, CH3C=O), 2.02 (s, 3H, CH3C=O), 2.04 (s, 3H, CH3C=O), 2.05 (s, 3H, CH3C=O), 2.44 (s, 3H, Het-CH3), 3.77–3.82 (m, 1H), 4.08–4.13 (m, 1H), 4.24 (dd, J = 12.9, 4.8 Hz, 1H), 5.07–5.16 (m, 2H), 5.28 (t, J = 9.3 Hz, 1H), 5.54 (d, J = 10.5 Hz, 1H), 6.60 (s, 1H, HetH), 6.84–7.51 (m, 4 H, ArH). Anal. Calcd. for C26H27BrN4O10S: C, 46.78; H, 4.08; N, 8.39. Found: C, 46.45; H, 3.83; N, 8.20.(2g)Yield 62%. Mp 90–92°C. −6° (c 1, CH2Cl2). 1H NMR (300 MHz, CDCl3): δ 1.95 (s, 3H, CH3C=O), 1.97 (s, 3H, CH3C=O), 1.98 (s, 3H, CH3C=O), 2.00 (s, 3H, CH3C=O), 2.42 (s, 3H, Het-CH3), 3.75–3.80 (m, 1H), 3.99–4.09 (m, 1H), 4.17–4.22 (m, 1H), 4.99–5.12 (m, 2H), 5.24 (t, J = 9.0 Hz, 1H), 5.49–5.55 (m, 1H), 6.64 (s, 1H, HetH), 6.86–7.54 (m, 4 H, ArH). Anal. Calcd. for C26H27ClN4O10S: C, 50.12; H, 4.37; N, 8.99. Found: C, 49.75; H, 4.10; N, 8.65.(2h)Yield 59%. Mp 157-158°C. 1° (c 1, CH2Cl2). 1H NMR (300 MHz, CDCl3): δ 1.98 (s, 3H, CH3C=O), 2.00 (s, 3H, CH3C=O), 2.01 (s, 3H, CH3C=O), 2.03 (s, 3H, CH3C=O), 2.43 (s, 3H, Het-CH3), 3.75–3.80 (m, 1H), 4.09 (dd, J = 12.3, 1.8 Hz, 1H), 4.22 (dd, J = 12.3, 4.5 Hz, 1H), 5.04–5.14 (m, 2H), 5.26 (t, J = 9.0 Hz, 1H), 5.52 (d, J = 9.9 Hz, 1H), 6.61 (s, 1H, HetH), 6.86 (d, J = 8.1 Hz, 1H, ArH), 7.05–7.63 (m, 3H, ArH). Anal. Calcd. for C26H27ClN4O10S: C, 50.12; H, 4.37; N, 8.99. Found: C, 49.91; H, 4.21; N, 8.66.(2i)Yield 54%. Mp 170-171°C. 1° (c 1, CH2Cl2). 1H NMR (300 MHz, CDCl3): δ 2.00 (s, 3H, CH3C=O), 2.01 (s, 3H, CH3C=O), 2.02 (s, 3H, CH3C=O), 2.03 (s, 3H, CH3C=O), 2.43 (s, 3H, Het-CH3), 3.77–3.83 (m, 1H), 4.08–4.12 (m, 1H), 4.23 (dd, J = 12.3, 4.8 Hz, 1H), 5.07–5.15 (m, 2H), 5.28 (t, J = 9.0 Hz, 1H), 5.57 (d, J = 10.2 Hz, 1H), 6.60 (s, 1H, HetH), 6.88 (d, J = 7.5 Hz, 1H, ArH), 7.05–7.46 (m, 3H, ArH). Anal. Calcd. for C26H27ClN4O10S: C, 50.12; H, 4.37; N, 8.99. Found: C, 49.88; H, 4.06; N, 8.73.General procedure for Preparation of 3-S-(2′,3′,4′,6′-tetrahydroxy-β-D-glucopyranosyl)-4-aryl-5-(5-methylisoxazol-3-yl)-1,2,4-triazoles(3a~3i).

Dry gaseous ammonia was passed at 0°C for about 1 h into a solution of 2a~2i(1 mmol) in dry MeOH. Then, the mixture was stirred at 25°C, and the reaction was monitored by TLC. The solution was concentrated, and the analytical pure product was obtained directly by recrystallization from methanol or methanol-petroleum ether.(3a) Yield 91.5%. Mp 134-135°C. −46° (c 1, CH3OH). 1H NMR (300 MHz, D2O): δ 2.36 (s, 6H, Ph-CH3 and Het-CH3), 3.29–3.39 (m, 3H), 3.41–3.47 (m, 1H), 3.57–3.63 (m, 1H), 3.76 (d, J = 12.3 Hz, 1H), 4.83–4.86 (m, 1H), 6.33 (s, 1H, HetH), 6.99–7.53 (m, 5H, ArH). Anal. Calcd. for C18H20N4O6S: C, 51.42; H, 4.79; N, 13.33. Found: C, 51.14; H, 4.66; N, 12.94.(3b): Yield 85%. Mp 122-123°C. −45° (c 1, CH3OH). 1H NMR (300 MHz, D2O): δ 1.92 (s, 3H, Ar-CH3), 2.36 (s, 3H, Het-CH3), 3.29–3.37 (m, 4H), 3.60–3.66 (m, 1H), 3.76 (t, J = 12.3 Hz, 1H), 4.95–4.99 (m, 1H), 6.34 (s, 1H, HetH), 7.00–7.20 (m, 4H, ArH). Anal. Calcd. for C19H22N4O6S: C, 52.52; H, 5.10; N, 12.90. Found: C, 52.29; H, 5.01; N, 12.56.(3c) Yield 94%. Mp 148–150°C.  −44° (c 1, CH3OH). 1H NMR (300 MHz, D2O): δ 2.36 (s, 6H, Het-CH3), 3.25–3.35 (m, 3H), 3.41–3.47 (m, 1H), 3.55–3.60 (m, 1H), 3.72 (d, J = 11.7 Hz, 1H), 4.87 (d, J = 9.9 Hz, 1H), 6.31 (s, 1H, HetH), 6.96–7.56 (m, 4H, ArH). Anal. Calcd. for C19H22N4O6S: C, 52.52; H, 5.10; N, 12.90. Found: C, 52.34; H, 5.02; N, 12.77.(3d) Yield 89%. Mp 125–127°C.  −48° (c 1, CH3OH). 1H NMR (300 MHz, D2O): δ 2.34 (s, 3H, Het-CH3), 3.24–3.48 (m, 7H), 3.57–3.63 (m, 1H), 3.68 (s, 3H, CH3O), 3.70–3.76 (m, 1H), 4.83–4.90 (m, 1H), 6.34 (s, 1H, HetH), 6.96–7.54 (m, 4H, ArH). Anal. Calcd. for C19H22N4O7S: C, 50.66; H, 4.92; N, 12.44. Found: C, 50.38; H, 5.04; N, 12.11.(3e) Yield 93%. Mp 145–147 °C.   −57° (c 1, CH3OH). 1H NMR (300 MHz, D2O): δ 2.36 (s, 3H, Het-CH3), 3.26–3.44 (m, 4H), 3.57–3.62 (m, 1H), 3.69–3.76 (m, 1H), 6.42 (s, 1H, HetH), 6.99–7.71 (m, 4H, ArH). Anal. Calcd. for C18H19BrN4O6S: C, 43.30; H, 3.84; N, 11.22. Found: C, 43.48; H, 4.15; N, 11.03.(3f) Yield 91%. Mp 140–142 °C. −29° (c 1, CH3OH). 1H NMR (300 MHz, D2O): δ 2.35 (s, 3H, Het-CH3), 3.29–3.39 (m, 3H), 3.41–3.47 (m, 1H), 3.57–3.63 (m, 1H), 3.76 (d, J = 12.3 Hz, 1H), 4.83–4.86 (m, 1H), 6.42 (s, 1H, HetH), 7.03–7.38 (m, 4H, ArH). Anal. Calcd. for C18H19BrN4O6S: C, 43.30; H, 3.84; N, 11.22. Found: C, 43.48; H, 4.08; N, 3.52.(3g) Yield 83%. Mp 144–146 °C.  −73° (c 1, CH3OH). 1H NMR (300 MHz, D2O): δ 2.33 (s, 3H, Het-CH3), 3.21–3.37 (m, 3H), 3.39–3.48 (m, 1H), 3.52–3.61 (m, 1H), 3.67–3.75 (m, 1H), 6.43 (s, 1H, HetH), 6.95–7.63 (m, 4H, ArH). Anal. Calcd. for C18H19ClN4O6S: C, 47.53; H, 4.21; N, 12.32. Found: C, 47.81; H, 4.36; N, 12.08.(3h) Yield 90%. Mp 130–132 °C. −44° (c 1, CH3OH). 1H NMR (300 MHz, D2O): δ 2.35 (s, 3H, Het-CH3), 3.30–3.34 (m, 3H), 3.41–3.47 (m, 1H), 3.55–3.61 (m, 1H), 3.74 (d, J = 11.1 Hz, 1H), 4.83 (d, J = 10.2 Hz, 1H), 6.42 (s, 1H, HetH), 7.02–7.44 (m, 4H, ArH). Anal. Calcd. for C18H19ClN4O6S: C, 47.53; H, 4.21; N, 12.32. Found: C, 47.65; H, 4.34; N, 12.10.(3i) Yield 92%. Mp 138–140 °C. −40° (c 1, CH3OH). 1H NMR (300 MHz, D2O): δ 2.35 (s, 3H, Het-CH3), 3.28–3.36 (m, 3H), 3.41–3.43 (m, 1H), 3.56–3.62 (m, 1H), 3.75 (d, J = 12.3 Hz, 1H), 6.42 (s, 1H, HetH), 7.02–7.44 (m, 4H, ArH). Anal. Calcd. for C18H19ClN4O6S: C, 47.53; H, 4.21; N, 12.32. Found: C, 47.33; H, 4.29; N, 12.02.

3. Results and Discussion

5-Methylisoxazole-3-carbohydrazide, which is required as a starting material, was prepared according to the literature [16]. As shown in Scheme 1, 4-aryl-5-(5-methylisoxazol-3-yl)-1,2,4-triazol-3-thiols (1a-1i) were prepared via the reaction of 5-methylisoxazole-3-carbohydrazide with arylisothiocyanates and then cyclization in the presence of 2 mol/L aqueous potassium carbonate solution.

S-β-D-acetylglucosides (2a-2i) were obtained with the improved Koenigs-Knorr method. We use potassium hydroxide as the base to avoid the use of more expensive or toxic reagents as prometers, such as phase transfer catalyst (BnEt3N+ Br) [18] or heavy metal salts (Hg(CN)2) [13]. The coupling reaction of 4-aryl-5-(5-methylisoxazol-3-yl)-1,2,4-triazol-3-thiols with 2,3,4,6-tetra-O-acetyl-α-D-glucopyranosyl bromide was conducted in ethanol in the presence of potassium hydroxide, and nine new S-β-D-acetylglucosides were afforded. The results showed that the reaction is a typical SN2 reaction and a convenient method to stereoselectively synthesis of only the single β-anomer.

The classical method of deacetylation of the sugar moiety employing a catalytic amount of sodium methoxide in methanol is described by Zemplén and Kuntz [19]. However, the Zemplén deacetylation is not suitable for the deprotection of carbohydrates containing 5-methylisoxazole-substituted 1,2,4-triazole due to the instability of the isoxazole ring under strong basic condition. Finally, the removal of the protecting groups was easily achieved by treatment with dry ammonia gas in dry methanol. The final desired S-glucosides containing 5-methylisoxazole-substituted 1,2,4-triazole (3a-3i) were successfully obtained in good yields.

The structures of 2a-2i and 3a-3i were confirmed by elemental analyses and spectral data. The 1H NMR spectral data of compounds 2a-2i showed the presence of four acetyl groups through the four singlets in the region of 1.94–2.05 ppm. In addition, seven hydrogen atoms of the sugar moiety were also observed in these spectra. They exhibited multiplets at 3.75–5.58 ppm. Only β-anomer was obtained as judged by a doublet at δ 5.52–5.58 (JH1,H2  = 9.9–10.8 Hz) of the anomeric proton (H-1) in the sugar moiety. Compounds 2a-2i showed two singlets at δ 2.41–2.44 and 6.54–6.64, which were assigned to the protons of methyl and isoxazole ring, respectively.

The 1H NMR spectra of 3a-3i provided support to successful deacetylation reaction by the disappearance of the four sharp singlets in the region of 1.94–2.05 ppm as observed in the spectra of 2a-2i. The aryl groups of compounds 2a-2i and 3a-3i were found in the region of 6.84–7.71 ppm. The other 1H NMR spectral data was found approximately the same as observed in the case of the corresponding acetylated glucosides. The elemental analysis of these compounds was good agreement with calculated values.

Compounds 3a-3i were screened for their antibacterial activity against Escherichia coli and Staphylococcus aureus. The results showed that most of the compounds were inactive against these microorganisms. Further investigation on biological activities is in progress.

Acknowledgment

The authors gratefully acknowledge the financial support from Xinxiang Medical University.

References

  1. R. Romagnoli, P. G. Baraldi, O. Cruz-Lopez et al., “Synthesis and antitumor activity of 1,5-disubstituted 1,2,4-triazoles as cis-restricted combretastatin analogues,” Journal of Medicinal Chemistry, vol. 53, no. 10, pp. 4248–4258, 2010. View at Publisher · View at Google Scholar · View at Scopus
  2. J. Chen, X. Y. Sun, K. Y. Chai et al., “Synthesis and anticonvulsant evaluation of 4-(4-alkoxylphenyl)-3-ethyl-4H-1,2,4-triazoles as open-chain analogues of 7-alkoxyl-4,5-dihydro[1,2,4]triazolo[4,3-a]quinolines,” Bioorganic and Medicinal Chemistry, vol. 15, no. 21, pp. 6775–6781, 2007. View at Publisher · View at Google Scholar
  3. J. Xu, Y. Cao, J. Zhang et al., “Design, synthesis and antifungal activities of novel 1,2,4-triazole derivatives,” European Journal of Medicinal Chemistry, vol. 46, no. 7, pp. 3142–3148, 2011. View at Publisher · View at Google Scholar · View at Scopus
  4. Y. M. Ma, R. H. Liu, X. Y. Gong et al., “Synthesis and Herbicidal Activity of N,N-Diethyl-3-(arylselenonyl)-1H-1,2,4-triazole-1-carboxamide,” Journal of Agricultural and Food Chemistry, vol. 54, no. 20, pp. 7724–7728, 2006. View at Publisher · View at Google Scholar
  5. X. P. Hui, L. M. Zhang, Z. Y. Zhang, Q. Wang, and F. Wang, “Synthesis and biological activity of 1,3,4-oxadiazole, 1,3,4-thiadiazole and 1,2,4-triazole derivatives of 5-methylisoxazole,” Indian Journal of Chemistry B, vol. 38, article 679, 1999. View at Google Scholar
  6. X. P. Hui, L. M. Zhang, Z. Y. Zhang, Q. Wang, and F. Wang, “Synthesis and antibacterial activity of s-Triazoles, s-Triazolo[3,4-b]-1,3,4-thiadiazines and s-Triazolo[3,4-b]-1,3,4-thiadiazoles of 5-Methylisoxazole,” Journal of the Chinese Chemical Society, vol. 47, article 535, 2000. View at Google Scholar
  7. Y. L. Gao, G. L. Zhao, M. Liu, Y. L. Wang, W. R. Xu, and J. W. Wang, “Thiadiazole-based thioglycosides as sodium-glucose co-transporter 2 (SGLT2) inhibitors,” Chinese Journal of Chemistry, vol. 28, no. 4, pp. 605–612, 2010. View at Publisher · View at Google Scholar
  8. V. Liska, J. E. Dyr, J. Suttnar, I. Hirsch, and V. Vonka, “Production and simple purification of a protein encoded by part of the gag gene of HIV-1 in the Escherichia coli HB101F+ expression system inducible by lactose and isopropyl-β-d-thiogalactopyranoside,” Journal of Chromatography B, vol. 656, no. 1, pp. 127–133, 1994. View at Publisher · View at Google Scholar
  9. J. T. Witkoski, R. K. Robins, R. W. Sidwell, and L. N. Simon, “Design, synthesis, and broad spectrum antiviral activity of 1-.beta.-D-ribofuranosyl-1,2,4-triazole-3-carboxamide and related nucleosides,” Journal of Medicinal Chemistry, vol. 15, no. 11, pp. 1150–1154, 1972. View at Publisher · View at Google Scholar
  10. R. A. Smith and W. Kirkpatrick, Eds., Ribavirin, A Broad Spectrum Antiviral Agent, Academic Press, New York, NY, USA, 1980.
  11. R. A. Smith, V. Knight, and J. A. D. Smith, Clinical Applications of Ribavirin, Academic Press, New York, NY, USA, 1984.
  12. G. D. Kini, R. K. Robins, and T. L. Avery, “Synthesis and antitumor activity of ribavirin imidates. New facile synthesis of ribavirin amidine (1-.beta.-D-ribofuranosyl-1,2,4-triazole-3-carboxamidine hydrochloride),” Journal of Medicinal Chemistry, vol. 32, no. 7, pp. 1447–1449, 1989. View at Publisher · View at Google Scholar
  13. K. Zamani, K. Faghihi, and R. Iqbal, “Synthesis and structure determination of some new N-glycosides of 4,5-disubstituted-1,2,4-triazole-3-thiones,” Journal of the Chinese Chemical Society, vol. 49, no. 6, pp. 1041–1044, 2002. View at Google Scholar
  14. N. A. Hassan, “Syntheses of acyclic C-glycosidic derivatives of 1,2,4-triazoles by cycloadditions of 1-aza-2-azoniaallene salts to D-glucononitrile-2,3,4,5,6-pentaacetate,” Journal of Heterocyclic Chemistry, vol. 44, no. 4, pp. 933–936, 2007. View at Publisher · View at Google Scholar
  15. W. A. El-Sayed, R. E. Abdel Megeid, and H. S. Abbas, “Synthesis and antimicrobial activity of new 1-[(tetrazol-5-yl)methyl] indole derivatives, their 1,2,4-triazole thioglycosides and acyclic analogs,” Archives of Pharmacal Research, vol. 34, no. 7, pp. 1085–1096, 2011. View at Publisher · View at Google Scholar
  16. C. S. Marvel, “Studies on acyl thiosemicarbazides and related heterocycles (V)—syntheses of 1-isonicotinoyl-4-aryl thiosemicarbazides and related nitrogen, sulfur, oxygen 5-membered heterocycles,” Organic Syntheses, vol. 1, article 238, 1951. View at Google Scholar
  17. Z. Y. Zhang, K. X. Yang, and F. L. Zeng, Chemical Journal of Chinese Universities, vol. 9, p. 239, 1988.
  18. Z. F. Wang, G. L. Zhao, W. Liu et al., “Design, synthesis and anti-diabetic activity of thiadiazole-based thioglycosides as SGLT2 inhibitors,” Chinese Journal of Organic Chemistry, vol. 30, no. 6, pp. 849–859, 2010. View at Google Scholar
  19. G. Zemplén and A. Kuntz, “Studien über Amygdalin, IV: Synthese des natürlichen l-Amygdalins,” Berichte der Deutschen Chemischen Gesellschaft B, vol. 57, no. 8, pp. 1357–1359, 1924. View at Publisher · View at Google Scholar