A convenient Synthesis of 6-amino-1-β-D-ribofuranosylpyrazolo[3,4-d] Pyrimidin-4-one and related 4,6-disubstltuted pyrazodopyrimidine nucleosldes

Abstract

The glycosylation of 4,6-dichloropyrazolo[3,4-d]pyrimidine and 4-chloro-6-methylthiopyrazolo[3,4-d]pyrimidine via the corresponding trimethylsilyl intermediate and tetra-O-acetyl-beta-D-ribofuranose in the presence of trimethylsilyl triflate as a catalyst, gave selective glycosylation at N1 as the only nucleoside product. The intermediates 4,6-dichloro-1-(2,3,5-tri-O-acetyl-beta-D-ribofuranosyl)pyrazolo [3,4-d]pyrimidine 7 and 4-chloro-6-methylthio-1-(2,3,5-tri-O-acetyl-beta-D-ribofuranosyl)pyrazolo [3,4-d]pyrimidine 13 gave new and convenient synthetic routes to the inosine analog 1, the guanosine analog 2, the adenosine analog 3, and the isoguanosine analog 16. Glycosylation of the trimethylsilyl derivative of 6-chloropyrazolo[3,4-d]pyrimidine-4-one unexpectedly gave the N2-glycosyl isomer 20 as the major product. A number of new 4,6-disubstituted pyrazolo[3,4-d]pyrimidine nucleosides were prepared from these glycosyl intermediates.

Pyrazolo[3,4-d]pyrimidine ribonucleosides related to 2-aminoadenosine and isoguanosine: synthesis, deamination and tautomerism

“…(ii) The glycosylation of 2,6-substituted 8-aza-7-deazapurines via the corresponding trimethylsilyl intermediates with tetra-Oacetyl-b-D-ribofuranose and trimethylsilyl triflate as catalyst. 31 (iii) Cottam et al (iv) Recently, Bookser and Raffaele 32 investigated the direct glycosylation of 8-aza-7-deazapurine with microwave assistance.…”

Polycytidylate and poly(7-deazaguanylate): A pair of complementary templates

“…Poly(C) was obtained from Sigma, polynucleotide phosphorylase (M. luteus) from Pharmacia; RNase T 1 (Asperigillus oryzae) from Boehringer; and inosine and 7-methyl guanosine (VI, 7-MEG) from Aldrich. We converted 7-deaza guanosine (III, cVG) Hasselmann 1980, 1981), 7-deaza-8-aza guanosine (IV, cTNSG) (Cottam et al 1983), 7-bromo-7-deaza-8-aza guanosine (V, 7-BrcYNSG) (Petrie III et al 1985), and 7-methyl-8-oxoguanosine (VII, 7-MeoSG) to their 5'-phosphoro(2-methyl)imidazolides by published procedures (Joyce et al 1984;Yoshikawa et al 1969). The purity of the products was assessed by thin-layer chromotography (TLC) (solvent: npropanol:ammonium hydroxide:water 55:10:35 by volume).…”

Synthesis and biological activity of 6-azacadeguomycin and certain 3,4,6-trisubstituted pyrazolo[3,4-d]pyrimidine ribonucleosides

“…This compound was identical in all respects with Id, prepared and reported recently from our laboratory. 25 3-Carbamoyl-6-thioxo-l,5,6,7-tetrahydropyrazolo[3,4-d']pyrimidin-4-one (13). A mixture of 5-aminopyrazole-3,4-di-carboxamide31 (12; 2.0 g, 12 mmol) and potassium ethyl xanthate (3.8 g, 24 mmol) in DMF (180 mL) was heated under reflux for 2 h. The reaction mixture was cooled in an ice bath and the precipitated product was collected by filtration.…”

“…The structural assignment of 7a was accomplished by debromination of 7a to provide the guanosine analogue Id, whose structure has been established previously from our laboratory. 25 In an effort to develop a synthetic procedure that would lead to guanosine analogues on a scale more suitable for preparative work, the use of other pyrazolo [3,4-d]pyrimidine bases for glycosylation studies was investigated. Thus, when 6-(methylthio)pyrazolo [3,4-d]pyrimidin-4-{5H)-one9 (5) was heated with bromine-water in the presence of sodium acetate (used as a buffer), 3-bromo-4(5H)-oxopyrazolo [3,4-d]pyrimidin-6-yl methyl sulfoxide (8) was obtained in 85% yields.…”