Solid-phase Parallel Synthesis of 4-β-D-Ribofuranosylpyrazolo[4,3-d]pyrimidine Nucleosides.

Autor: Ramasamy, KandaS., Amador, RobertoB., Habib, Qazi, Rong, Frank, Han, Xiaogang, Li, DavidY., Huang, Jingfan, Hong, Zhi, An, Haoyun
Předmět:
Zdroj: Nucleosides, Nucleotides & Nucleic Acids; Oct2005, Vol. 24 Issue 10-12, p1947-1970, 24p, 7 Diagrams, 3 Charts, 1 Graph
Abstrakt: 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. [ABSTRACT FROM AUTHOR]
Databáze: Complementary Index
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