Synthesis of 2,6-dioxatricyclo[3.3.1.0]nonanes by intramolecular haloetherification and/or transannular hydroxycyclization of alkenes in [4+3]-cycloadducts |
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Authors: | Ángel M Montaña Juan A Barcia Mercè Font-Bardía |
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Institution: | a Unidad de Química Orgánica Industrial y Aplicada, Departamento de Química Orgánica, Facultad de Química, Universidad de Barcelona, c/Martí i Franquès, 1-11, 08028 Barcelona, Spain b Crystallography Services, Department of Chemistry, University of Bath, Bath BA2 7AY, UK c Departamento de Cristalografía, Mineralogía y Depósitos Minerales, Universidad de Barcelona, Martí i Franquès s/n, 08028-Barcelona, Spain |
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Abstract: | The synthesis of new difunctionalized 2,6-dioxatricyclo3.3.1.03,7]nonanes is described. This type of structure is an interesting synthetic building block for potential bioactive molecules and it was prepared from 8-oxabicyclo3.2.1]oct-6-en-3-one having a NHBoc function on C-1. This precursor was obtained by a 4+3] cycloaddition reaction of 2-tert-butoxycarbonylaminofuran and the oxyallyl cation generated in situ from 2,4-dibromo-3-pentanone. Reduction of the carbonyl group at C-3 was accomplished in high yield and stereoselective manner to afford the corresponding axial alcohol at C-3 as a major product. Further intramolecular haloetherification of this type of alcohols with NBS and I(py)2BF4 led to the corresponding bromo and iodo-derivatives at C-8 of the 2,6-dioxatricyclo3.3.1.03,7]nonane framework, in high yield. Epoxidation of 8-oxabicyclo3.2.1]oct-6-en-3-ol followed by treatment with NaCN, NaN3, and/or NaOH in MeOH afforded 8-hydroxy-2,6-dioxatricyclo3.3.1.03,7]nonanes in high yield via a transannular hydroxycyclization mediated by a base and through an alkoxide intermediate. The new 2,6-dioxatricyclo3.3.1.03,7]nonanes were tested for biological activity against HIV-1 virus and MT-4 lymphoid cell line, showing a low anti-HIV activity and a high degree of cytotoxicity. |
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Keywords: | [4+3] Cycloaddition 8-Oxabicyclo[3 2 1]oct-6-en-3-one 2 6-Dioxatricyclo[3 3 1 03 7]nonanes Haloetherification Transannular hydroxycyclization |
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