Enantiospecific Total Synthesis of l -2‘,3‘-Dideoxyisonucleosides via Regioselective Opening of Optically Active C2-Symmetric 1,4-Pentadiene Bis-epoxide1
| Autor: | Oliver Kretschik, Michael E. Jung |
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| Rok vydání: | 1998 |
| Předmět: | |
| Zdroj: | The Journal of Organic Chemistry. 63:2975-2981 |
| ISSN: | 1520-6904 0022-3263 |
| DOI: | 10.1021/jo9721655 |
| Popis: | A new method for the synthesis of l-2‘,3‘-dideoxyisonucleosides is described. The readily available, optically active C2-symmetric bis-epoxide (2S,4S)-1,2:4,5-diepoxypentane (5) was prepared by a short route from readily available starting materials. The key step of the new synthesis is the opening of 5 with nucleophiles, which proceeds highly regioselectively; e.g., reaction with sodium sulfide affords a 5:1 mixture of the tetrahydrothiophenediol 9a and the tetrahydrothiopyrandiol 14, and reaction with sodium hydroxide gives exclusively the tetrahydrofurandiol 9b via a preferred 5-exo cyclization. These five-membered diols 9a,b can be converted in only four steps into the modified dideoxyuridine and adenosine isonucleosides 4a−c, one of which (4c) has shown good antiviral activity. In addition, we have examined the opening of the analogous six-carbon bis-epoxide, (2S,5S)-1,2:5,6-diepoxyhexane (23), which affords a 3:1 mixture of the hexahydrothiepinediol 24 and the tetrahydrothiopyrandiol 25 with sodium ... |
| Databáze: | OpenAIRE |
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