Application of the Michaelis–Arbusov reaction to the synthesis of internucleoside 3′-S-phosphorothiolate inkages
| Autor: | Gerard K. Scott, Anthony David Baxter, Joseph S. Vyle, Roger John Taylor, Xiang Li, Richard Cosstick |
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| Rok vydání: | 1994 |
| Předmět: | |
| Zdroj: | J. Chem. Soc., Perkin Trans. 1. :2123-2129 |
| ISSN: | 1364-5463 0300-922X |
| DOI: | 10.1039/p19940002123 |
| Popis: | The 5′-O-monomethoxytrityl-3′-S-(aryldisulfanyl)-3′-deoxythymidines 7 and 8 have been prepared by the reaction of 5′-O-monomethoxytrityl-3′-thiothymidine with the appropriate arenesulfenyl chloride. These disulfides undergo a Michaelis–Arbusov reaction with simple trialkyl phosphites to yield 5′-O-monomethoxytrityl-3′-thiothymidin-3′-yl O,O-dialkyl phosphorothiolates. More interestingly, 3′-deoxy-3′-S-(2, 4-dinitrophenylsulfanyl)-5′-O-monomethoxytritylthymidine 8 reacts with a variety of thymidin-5′-yl dialkyl phosphites to give dithymidine phosphorothiolate triesters with the phosphorothiolate group protected with either a methyl or a 2-cyanoethyl group.3′-O-(tert-Butyldimethylsilyl)thymidin-5′-yl triethylammoniumphosphonate 17 is converted into the corresponding bis-(O-trimethylsilyl) phosphite by treatment with bis(trimethylsilyl)trifluoroacetamide. in situ Reaction of this phosphate with disulfide 8 gives, after work-up, the dithymidine phosphorothiolate diester directly. Methylation of compound 17 with methyl chloromethanoate, followed by silylation and subsequent reaction with disulfide 8, gives the methyl-protected dithymidine phosphorothiolate triester. |
| Databáze: | OpenAIRE |
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