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.

The structural identification of the isomeric disubstituted pyrazolyl nucleosides, based on their 1 H NMR spectral data (See Supplementary Materials), has been reported in the literature [46] [47] [48] . It has been observed that the anomeric protons in the isomeric pyrazolyl nucleosides exhibit different proton chemical shifts. The anomeric proton adjacent to N-1 of the pyrazole compounds 3a-e and 5a-e would appear downfield when compared to the anomeric proton adjacent to N-2 of the pyrazole compounds 4a-e and 6a-e [46] [47] [48] . In addition to using 1 H NMR chemical shifts, extensive NOE and 2D NMR experiments have been employed to confirm the structures of the isomeric pyrazolyl nucleosides. Using 1 H and 13 C NMR studies, we confirmed the positional assignments of the isomeric pyrazolyl nucleosides synthesized in the present work (Tables 1-3 ). The anomeric proton of the analogues 5a-e generally appeared at 0.14-0.19 ppm upfield when compared to the corresponding proton in the 1 H NMR spectra of its corresponding 6 series isomers. This is in agreement with observations for other 1,5-and 1,3-disubstituted pyrazole nucleosides [46] [47] [48] . We Pyrazoles with no substitution on either of the two N ring atoms can be alkylated to produce two regioisomers under strongly basic conditions. The anion generated produces the two resonance forms that react with chlorosugar 2 in the glycosidation step, leading to mixtures of two regioisomeric pyrazolyl nucleosides (i.e., 3a-e and 4a-e) (Scheme 2). Pyrazoles with no substitution on either of the two N ring atoms can be alkylated to produce two regioisomers under strongly basic conditions. The anion generated produces the two resonance forms that react with chlorosugar 2 in the glycosidation step, leading to mixtures of two regioisomeric pyrazolyl nucleosides (i.e., 3a-e and 4a-e) (Scheme 2).