title: Solid-phase parallel synthesis of 4-beta-D-ribofuranosylpyrazolo[4,3-d]pyrimidine nucleosides.
abstract: The synthesis of pyrazolo[4,3-d]pyrimidine nucleoside library using solid-phase parallel synthesis methodology is described. Glycosylation of the trimethylsilyl (TMS) derivative of 1- and 2-(methyl)-1H and 2H-pyrazolo[4,3-d]pyrimidine-5,7-(4H, 6H)-dione (5) with 1-O-acetyl-2,3,5-tri-O-benzoyl-D-ribofuranose in the presence of TMS triflate provided two novel protected nucleosides 6 and 7. The structures of 6 and 7 were assigned by 1H and 2D NMR experiments. Nucleosides 6 and 7 were then transformed to the key intermediates 12 and 15 respectively. Reaction of 12 and 15 with MMTCl resin in the presence of 2,6-lutidine afforded the necessary scaffolds B and C. Different amines (96) were introduced selectively by nucleophilic substitution on scaffolds B and C using solid-phase parallel semi-automated synthesizer. Cleavage of the products from the solid support with 30% HFIP in a parallel fashion yielded nucleoside libraries simultaneously, and they were analyzed and characterized by high-throughput LC-MS.
authors.affiliation: R & D Division, Valeant Pharmaceuticals, Costa Mesa, California 92626, USA. kramasamy@valeant.com
authors.forename: Kanda S
authors.initials: KS
authors.lastname: Ramasamy
authors.forename: Roberto B
authors.initials: RB
authors.lastname: Amador
authors.forename: Qazi
authors.initials: Q
authors.lastname: Habib
authors.forename: Frank
authors.initials: F
authors.lastname: Rong
authors.forename: Xiaogang
authors.initials: X
authors.lastname: Han
authors.forename: David Y
authors.initials: DY
authors.lastname: Li
authors.forename: Jingfan
authors.initials: J
authors.lastname: Huang
authors.forename: Zhi
authors.initials: Z
authors.lastname: Hong
authors.forename: Haoyun
authors.initials: H
authors.lastname: An
mesh_terms: D000493:Allopurinol / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry; D015394:Molecular Structure; D012263:Ribonucleosides / Q000138:chemical synthesis* / Q000737:chemistry
chemical_list: D012263:Ribonucleosides; D000493:Allopurinol; C021958:allopurinol riboside