Synthetic, Structural, and Anticancer Activity Evaluation Studies on Novel Pyrazolylnucleosides

Yadav, Yogesh; Sharma, Deepti; Kaushik, Kumar; Kumar, Vineet; Jha, Amitabh; Prasad, Ashok K.; Len, Christophe; Malhotra, Sanjay V.; Wengel, Jesper; Parmar, Virinder S.

A solution of 3-cyanomethyl-5-arylpyrazole (1a-e, 15 mmol) in acetonitrile (190 mL) was added into a stirred mixture of sodium hydride (22.5 mmol) in acetonitrile (30 mL) under a nitrogen atmosphere at 30-35 • C, and continuously stirred for 30 min. The reaction mixture was cooled to 0 • C and 1-α-chloro-3,5-di-O-toluoyl-1,2-dideoxyribose (2, 15 mmol) was added and the contents stirred at 0 • C for 2.5 to 3 h. The progress of the reaction was monitored by using silica gel TLC. On completion, the reaction mixture was poured over ice-cold water and extracted with ethyl acetate (3 × 50 mL). The combined organic layer was washed with water (2 × 50 mL), dried over anhydrous sodium sulfate, the solvent was removed under reduced pressure, and the residue thus obtained was column chromatographed over silica gel with ethyl acetate (8-10%) in petroleum ether as the eluent to afford the pyrazolyl nucleosides 3a-e and 4a-e in 31 to 35% and 24 to 29% yields, respectively. 13 13 was suspended in dry methanol (18 mL), then a mixture of NaOMe and MeOH (10 mL, 1:3, v/v) was added to the resulting solution, and the contents stirred at room temperature for 3-4 h. The progress of the reaction was monitored by using silica gel TLC. On completion, NH 4 Cl was added to the reaction mixture to adjust the pH to 8. One-third of the solvent was removed under reduced pressure and the reaction mixture was poured in water and extracted with ethyl acetate (3 × 30 mL), the organic layer was dried over anhydrous sodium sulfate, the solvent was removed under reduced pressure, and the residue thus obtained was subjected to column chromatography over silica gel with methanol (2-2.5%) in chloroform as the eluent to afford 2 -deoxy-1 -(3-cyanomethyl-5-aryl)pyrazolyl-β-d-ribofuranose (5a-e) and 2 -deoxy-1 -(3-aryl-5-cyanomethyl)pyrazolyl-β-d-ribofuranose (6a-e).