Design,Synthesis, and Antiviral Evaluation of Some Polyhalogenated Indole C-nucleosides |
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| Authors: | Jiong J Chen Yuan Wei John D Williams John C Drach Leroy B Townsend |
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| Institution: | 1. Department of Chemistry , College of Literature, Sciences and the Arts, University of Michigan , Ann Arbor, Michigan, USA;2. Department of Medicinal Chemistry , College of Pharmacy, University of Michigan , Ann Arbor, Michigan, USA;3. Department of Medicinal Chemistry , College of Pharmacy, University of Michigan , Ann Arbor, Michigan, USA;4. Department of Biologic and Materials Sciences , School of Dentistry, University of Michigan , Ann Arbor, Michigan, USA;5. Department of Chemistry , College of Literature, Sciences and the Arts, University of Michigan , Ann Arbor, Michigan, USA |
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| Abstract: | 2,5,6-Trichloro-1-(β-D-ribofuranosyl)benzimidazole (TCRB), 2-bromo-5,6-dichloro-1-(β-D-ribofuranosyl)benzimidazole (BDCRB) and 2-benzylthio-5,6-dichloro-1-(β-D-ribofuranosyl)benzimidazole (BTDCRB) are benzimidazole nucleosides that exhibit strong and selective anti-HCMV activity. Polyhalogenated indole C-nucleosides were prepared as 1-deaza analogs of the benzimidazole nucleosides TCRB and BDCRB. A mild Knoevenagel coupling reaction between an indol-2-thione and a ribofuranose derivative was developed for the synthesis of 2-benzylthio-5,6-dichloro-3-(β-D-ribofuranosyl)indole (12). 3-(β-D-ribofuranosyl)-2,5,6-trichloroindole (16) was prepared from 12 in 4 steps. A Lewis acid-mediated glycosylation method was then developed to prepare the targeted 2-haloindole C-nucleoside 16 stereoselectively in four steps from the corresponding 2-haloindole aglycons. Only 12 was active against HCMV but it also was somewhat cytotoxic. |
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| Keywords: | Indole nucleoside C-Nucleoside Nucleoside analog Antiviral TCRB Human cytomegalovirus (HCMV) |
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