Synthesis of certain pyrazolo[3,4‐d]pyrimidin‐3‐one nucleosides

Abstract

Synthesis of the pyrazolo[3,4‐d]pyrimidin‐3‐one congeners of guanosine, adenosine and inosine is described. Glycosylation of 3‐methoxy‐6‐methylthio‐1H‐pyrazolo[3,4‐d]pyrimidin‐4(5H)‐one (13) with 1‐O‐acetyl‐2,3,5‐tri‐O‐benzoyl‐D‐ribofuranose (16) in the presence of boron trifluoride etherate gave 3‐methoxy‐6‐methylthio‐1‐(2,3,5‐tri‐O‐benzoyl‐β‐D‐ribofuranosyl)pyrazolo[3,4‐d]pyrimidin‐4(5H)‐one (17) which, after successive treatments with 3‐chloroperoxybenzoic acid and methanolic ammonia, afforded 6‐amino‐3‐methoxy‐1‐β‐D‐ribofuranosylpyrazolo[3,4‐d]pyrimidin‐4(5H)one (18). The guanosine analog, 6‐amino‐1‐β‐D‐ribofuranosylpyrazolo[3,4‐d]pyrimidine‐3,4(2H,5H)‐dione (21), was made by sodium iodide‐chlorotrimethylsilane treatment of 6‐amino‐3‐methoxy‐1‐(2,3,5‐tri‐O‐acetyl‐β‐D‐ribofuranosyl)pyrazolo[3,4‐d]pyrimidin‐4(5H)one (19), followed by sugar deprotection. Treatment of the adenine analog, 4‐amino‐1H‐pyrazolo[3,4‐d]pyrimidin‐3(2H)‐one (11), according to the high temperature glycosylation procedure yielded a mixture of N‐1 and N‐2 ribosyl‐attached isomers. Deprotection of the individual isomers afforded 4‐amino‐3‐hydroxy‐1‐βribofuranosylpyrazolo‐[3,4‐d]pyrimidine (26) and 4‐amino‐2‐β‐D‐ribofuranosylpyrazolo[3,4‐d]pyrimidin‐3(7H)‐one (27). The structures of 26 and 27 were established by single crystal X‐ray diffraction analysis. The inosine analog, 1‐β‐D‐ribofuranosylpyrazolo[3,4‐d]pyrimidine‐3,4(2H,5H)‐dione (28), was synthesized enzymatically by direct ribosylation of 1H‐pyrazolo[3,4‐d]pyrimidine‐3,4(2H,5H)‐dione (8) with ribose‐1‐phosphate in the presence of purine nucleoside phosphorylase, and also by deamination of 26 with adenosine deaminase.

Crystal structure of 3-(6-(5-amino-1-phenyl-1H-pyrazol-3-yl)pyridin-2-yl)-1-phenyl-1H-pyrazol-5-amine – dioxan (2/1), C25H23N7O

“…Pyrazole and fused heterocyclic pyrazole derivatives constute an interesting class of heterocycles due to their synthetic versatility and e ective biological activities [4]. Pyrazolo [3,4-d]pyridine derivatives have been found to possess antitumor and antileukemia activity [5]. On the other hand, a number of new 6-substituted 3-(pyridine-4-yl) 1,2,4-triazole [3,4-b] [1,3,4]thiadiazoles were synthesized and evaluated for their pharmacological activity.…”

Synthesis and Biological Activities of Novel 1,7-dihydropyrazolo[3,4-d]imidazo[1,2-f]pyrimidines

“…Spectra IR were recorded on a Perkin-Elmer PARAGON FT-IR spectrometer covering field 400-4000 cm -1 . The spectra of 1 H NMR and 13 C NMR was recorded in solution in CDCl 3 or in dimethylsulfoxide (DMSO-d 6 ) on a Bruker spectrometer ( 1 H at 400 MHz, 13 C at 100 MHz) and High resolution mass spectrometry (HRMS). The chemical shifts are expressed in parts per million (ppm) by using tetramethylsilane (TMS) as internal reference.…”

“…The product was filtered, washed with diethyl ether then purified by recrystallization (ethanol). 13 C RMN (δ ppm, DMSO-d 6 ): 114.14 (C-3a), 124.27 (C-2' and C-6'), 129.00 (C-4'), 129.58 (C-3' and C-5'), 130.04 (C-3), 136.94 (C-1'), 141.36 (C-7a), 149.83 (C-6), 156.84 (C-4); HRMS Calculated for C 11 (C-3a); 114.14 (C-3"), 114.49 (C-5"), 121.79 (C-5), 121.86 (C-3' and C-5'), 122.67 (C-6), 127.27 (C-1"), 127.38 (C-4'), 128.73 (C-2" and C-6"), 129.36 (C-2' and C-6'), 133.02 (C-3), 138.13 (C-1'), 139.06 (C-8), 139.95 (C-4a), 144.87 (C-9a), 159.79 (C-4"); HRMS Calculated for C 20 …”

“…The 5-amino-4-cyano-N 1 -phenylpyrazole 2, used as a starting material, was prepared in two steps following a similar method reported by Petrie and al [12][13][14]. The first step involves acid catalyzed condensation of orthoester with malonate to form ethoxymethylene malononitrile 1.…”

SYNTHESIS, CHARACTERIZATION AND ANTIOXIDANT STUDY OF 6-METHYL-2H-PYRAZOLO[3,4-d]PYRIMIDINE-3,4-DIAMINE AND ITS DERIVATIVES.

“…After lot of literature survey we came to know that pyrazolopyrimidines and related fused heterocycles attracted organic chemist very much due to their broad spectrum biological and chemotherapeutic importance. They are known to exhibit widespread pharmacological importance [3][4] and were reported to posses antibacterial [5], antifungal [6], anti-inflammatory [7], antiviral [8], analgesic [9], antitumor [10], CNS-depressant [11][12], neuroleptic [13], tuberculostatic [14], protein kinase inhibitors [15], HIV reverse transcriptase inhibitors [16], non-narcotic analgesic activities [17]. More over pyrazolo [3,4-d]pyrimidines identifies as general class of adenosine receptors [18][19][20].…”