Stereoselective Synthesis of 24-Fluoro-25-Hydroxyvitamin D<sub>3</sub> Analogues and Their Stability to hCYP24A1-Dependent Catabolism
Two 24-fluoro-25-hydroxyvitamin D<sub>3</sub> analogues (<b>3</b>,<b>4</b>) were synthesized in a convergent manner. The introduction of a stereocenter to the vitamin D<sub>3</sub> side-chain C24 position was achieved via Sharpless dihydroxylation, and...
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| Autores principales: | , , , , , |
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| Formato: | article |
| Lenguaje: | EN |
| Publicado: |
MDPI AG
2021
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| Materias: | |
| Acceso en línea: | https://doaj.org/article/2fbcff291b1f4b25a493701f37d86ed8 |
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| Sumario: | Two 24-fluoro-25-hydroxyvitamin D<sub>3</sub> analogues (<b>3</b>,<b>4</b>) were synthesized in a convergent manner. The introduction of a stereocenter to the vitamin D<sub>3</sub> side-chain C24 position was achieved via Sharpless dihydroxylation, and a deoxyfluorination reaction was utilized for the fluorination step. Comparison between (24<i>R</i>)- and (24<i>S</i>)-24-fluoro-25-hydroxyvitamin D<sub>3</sub> revealed that the C24-<i>R</i>-configuration isomer <b>4</b> was more resistant to CYP24A1-dependent metabolism than its 24<i>S</i>-isomer <b>3</b>. The new synthetic route of the CYP24A1 main metabolite (24<i>R</i>)-24,25-dihydroxyvitamin D<sub>3</sub> (<b>6</b>) and its 24<i>S</i>-isomer (<b>5</b>) was also studied using synthetic intermediates (<b>30</b>,<b>31</b>) in parallel. |
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