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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2021
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oai:doaj.org-article:2fbcff291b1f4b25a493701f37d86ed82021-11-11T17:17:16ZStereoselective Synthesis of 24-Fluoro-25-Hydroxyvitamin D<sub>3</sub> Analogues and Their Stability to hCYP24A1-Dependent Catabolism10.3390/ijms2221118631422-00671661-6596https://doaj.org/article/2fbcff291b1f4b25a493701f37d86ed82021-11-01T00:00:00Zhttps://www.mdpi.com/1422-0067/22/21/11863https://doaj.org/toc/1661-6596https://doaj.org/toc/1422-0067Two 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.Fumihiro KawagoeSayuri MototaniKaori YasudaHiroki ManoToshiyuki SakakiAtsushi KittakaMDPI AGarticlehuman CYP24A1synthesisvitamin D<sub>3</sub> metabolite24-fluoro-25-hydroxyvitamin D<sub>3</sub> analoguesSharpless dihydroxylationBiology (General)QH301-705.5ChemistryQD1-999ENInternational Journal of Molecular Sciences, Vol 22, Iss 11863, p 11863 (2021) |
| institution |
DOAJ |
| collection |
DOAJ |
| language |
EN |
| topic |
human CYP24A1 synthesis vitamin D<sub>3</sub> metabolite 24-fluoro-25-hydroxyvitamin D<sub>3</sub> analogues Sharpless dihydroxylation Biology (General) QH301-705.5 Chemistry QD1-999 |
| spellingShingle |
human CYP24A1 synthesis vitamin D<sub>3</sub> metabolite 24-fluoro-25-hydroxyvitamin D<sub>3</sub> analogues Sharpless dihydroxylation Biology (General) QH301-705.5 Chemistry QD1-999 Fumihiro Kawagoe Sayuri Mototani Kaori Yasuda Hiroki Mano Toshiyuki Sakaki Atsushi Kittaka Stereoselective Synthesis of 24-Fluoro-25-Hydroxyvitamin D<sub>3</sub> Analogues and Their Stability to hCYP24A1-Dependent Catabolism |
| description |
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. |
| format |
article |
| author |
Fumihiro Kawagoe Sayuri Mototani Kaori Yasuda Hiroki Mano Toshiyuki Sakaki Atsushi Kittaka |
| author_facet |
Fumihiro Kawagoe Sayuri Mototani Kaori Yasuda Hiroki Mano Toshiyuki Sakaki Atsushi Kittaka |
| author_sort |
Fumihiro Kawagoe |
| title |
Stereoselective Synthesis of 24-Fluoro-25-Hydroxyvitamin D<sub>3</sub> Analogues and Their Stability to hCYP24A1-Dependent Catabolism |
| title_short |
Stereoselective Synthesis of 24-Fluoro-25-Hydroxyvitamin D<sub>3</sub> Analogues and Their Stability to hCYP24A1-Dependent Catabolism |
| title_full |
Stereoselective Synthesis of 24-Fluoro-25-Hydroxyvitamin D<sub>3</sub> Analogues and Their Stability to hCYP24A1-Dependent Catabolism |
| title_fullStr |
Stereoselective Synthesis of 24-Fluoro-25-Hydroxyvitamin D<sub>3</sub> Analogues and Their Stability to hCYP24A1-Dependent Catabolism |
| title_full_unstemmed |
Stereoselective Synthesis of 24-Fluoro-25-Hydroxyvitamin D<sub>3</sub> Analogues and Their Stability to hCYP24A1-Dependent Catabolism |
| title_sort |
stereoselective synthesis of 24-fluoro-25-hydroxyvitamin d<sub>3</sub> analogues and their stability to hcyp24a1-dependent catabolism |
| publisher |
MDPI AG |
| publishDate |
2021 |
| url |
https://doaj.org/article/2fbcff291b1f4b25a493701f37d86ed8 |
| work_keys_str_mv |
AT fumihirokawagoe stereoselectivesynthesisof24fluoro25hydroxyvitamindsub3subanaloguesandtheirstabilitytohcyp24a1dependentcatabolism AT sayurimototani stereoselectivesynthesisof24fluoro25hydroxyvitamindsub3subanaloguesandtheirstabilitytohcyp24a1dependentcatabolism AT kaoriyasuda stereoselectivesynthesisof24fluoro25hydroxyvitamindsub3subanaloguesandtheirstabilitytohcyp24a1dependentcatabolism AT hirokimano stereoselectivesynthesisof24fluoro25hydroxyvitamindsub3subanaloguesandtheirstabilitytohcyp24a1dependentcatabolism AT toshiyukisakaki stereoselectivesynthesisof24fluoro25hydroxyvitamindsub3subanaloguesandtheirstabilitytohcyp24a1dependentcatabolism AT atsushikittaka stereoselectivesynthesisof24fluoro25hydroxyvitamindsub3subanaloguesandtheirstabilitytohcyp24a1dependentcatabolism |
| _version_ |
1718432109177077760 |