Synthesis and Antiviral Evaluation of Novel 2,3-Dihydroxypropyl Nucleosides from 2- and 4-Thiouracils |
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Authors: | Adel A-H Abdel-Rahman Abd-Allah SH El-Etrawy Ahmed E-S Abdel-Megied Ibrahim F Zeid El Sayed H El Ashry |
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Institution: | 1. Chemistry Department, Faculty of Science , Menoufia University , Shebin El-Koam, Egypt;2. Chemistry Department, Faculty of Science , Alexandria University , Alexandria, Egypt |
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Abstract: | Regioselective alkylation of 2-thiouracils 1a–c and 4-thiouracils 7a,b with 2,3-O-isopropylidene-2,3-dihydroxypropyl chloride (2) afforded 2-{(2,2-Dimethyl-1,3-dioxolan-4-yl) methyl]thio}pyrimidin-4(1H)-ones 3a–c and 4-{(2,2-Dimethyl-1,3-dioxolan-4-yl)methyl]thio} pyrimidin-2(1H)-ones 8a,b, respectively. Further alkylation with 2 and/or 2,3-O-isopropylidine-1-O-(4-toluenesulfonyl)-glycerol (4) gave the acyclo N-nucleosides 5a–c and 9a,b whose deprotection afforded 6a–c and 10a,b. 2-(Methylthio)pyrimidin-4(1H)-ones 11a–c and 4-(methylthio)pyrimidin-2(1H)-ones 14a,b were treated with 2 and/or 4 to give 12a–c and 15a,b which were deprotected to give 13a–c and 16a,b. Pyrimidine-2,4(1H,3H)-dithiones 17a–c were treated with two equivalents of 2 to give 2,4-bis{(2,2-dimethyl-1,3-dioxolan-4-yl)methyl]thio}pyrimidines 18a–c. Deprotection of compounds 18a–c gave 2,4-bis(2,3-dihydroxypropyl)thio]pyrimidines 19a-c. The activity of the deprotected nucleosides against Hepatitis B virus was evaluated and showed moderate inhibition activity against HBV with mild cytotoxicity. |
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Keywords: | Acyclic nucleosides 2 3-dihydroxypropyl nucleosides 2-(methylthio) pyrimidin-4(1H)-ones 4-(methylthio)pyrimidin-2(1H)-ones antiviral agents hepatitis B |
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