Stereoselective Synthesis of 24-Fluoro-25-Hydroxyvitamin D(3) Analogues and Their Stability to hCYP24A1-Dependent Catabolism

Two 24-fluoro-25-hydroxyvitamin D(3) analogues (3,4) were synthesized in a convergent manner. The introduction of a stereocenter to the vitamin D(3) side-chain C24 position was achieved via Sharpless dihydroxylation, and a deoxyfluorination reaction was utilized for the fluorination step. Comparison...

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Autores principales: Kawagoe, Fumihiro, Mototani, Sayuri, Yasuda, Kaori, Mano, Hiroki, Sakaki, Toshiyuki, Kittaka, Atsushi
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
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Article
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8584271/
https://www.ncbi.nlm.nih.gov/pubmed/34769295
http://dx.doi.org/10.3390/ijms222111863
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author Kawagoe, Fumihiro
Mototani, Sayuri
Yasuda, Kaori
Mano, Hiroki
Sakaki, Toshiyuki
Kittaka, Atsushi
author_facet Kawagoe, Fumihiro
Mototani, Sayuri
Yasuda, Kaori
Mano, Hiroki
Sakaki, Toshiyuki
Kittaka, Atsushi
author_sort Kawagoe, Fumihiro
collection PubMed
description Two 24-fluoro-25-hydroxyvitamin D(3) analogues (3,4) were synthesized in a convergent manner. The introduction of a stereocenter to the vitamin D(3) side-chain C24 position was achieved via Sharpless dihydroxylation, and a deoxyfluorination reaction was utilized for the fluorination step. Comparison between (24R)- and (24S)-24-fluoro-25-hydroxyvitamin D(3) revealed that the C24-R-configuration isomer 4 was more resistant to CYP24A1-dependent metabolism than its 24S-isomer 3. The new synthetic route of the CYP24A1 main metabolite (24R)-24,25-dihydroxyvitamin D(3) (6) and its 24S-isomer (5) was also studied using synthetic intermediates (30,31) in parallel.
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spelling pubmed-85842712021-11-12 Stereoselective Synthesis of 24-Fluoro-25-Hydroxyvitamin D(3) Analogues and Their Stability to hCYP24A1-Dependent Catabolism Kawagoe, Fumihiro Mototani, Sayuri Yasuda, Kaori Mano, Hiroki Sakaki, Toshiyuki Kittaka, Atsushi Int J Mol Sci Article Two 24-fluoro-25-hydroxyvitamin D(3) analogues (3,4) were synthesized in a convergent manner. The introduction of a stereocenter to the vitamin D(3) side-chain C24 position was achieved via Sharpless dihydroxylation, and a deoxyfluorination reaction was utilized for the fluorination step. Comparison between (24R)- and (24S)-24-fluoro-25-hydroxyvitamin D(3) revealed that the C24-R-configuration isomer 4 was more resistant to CYP24A1-dependent metabolism than its 24S-isomer 3. The new synthetic route of the CYP24A1 main metabolite (24R)-24,25-dihydroxyvitamin D(3) (6) and its 24S-isomer (5) was also studied using synthetic intermediates (30,31) in parallel. MDPI 2021-11-01 /pmc/articles/PMC8584271/ /pubmed/34769295 http://dx.doi.org/10.3390/ijms222111863 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Kawagoe, Fumihiro
Mototani, Sayuri
Yasuda, Kaori
Mano, Hiroki
Sakaki, Toshiyuki
Kittaka, Atsushi
Stereoselective Synthesis of 24-Fluoro-25-Hydroxyvitamin D(3) Analogues and Their Stability to hCYP24A1-Dependent Catabolism
title Stereoselective Synthesis of 24-Fluoro-25-Hydroxyvitamin D(3) Analogues and Their Stability to hCYP24A1-Dependent Catabolism
title_full Stereoselective Synthesis of 24-Fluoro-25-Hydroxyvitamin D(3) Analogues and Their Stability to hCYP24A1-Dependent Catabolism
title_fullStr Stereoselective Synthesis of 24-Fluoro-25-Hydroxyvitamin D(3) Analogues and Their Stability to hCYP24A1-Dependent Catabolism
title_full_unstemmed Stereoselective Synthesis of 24-Fluoro-25-Hydroxyvitamin D(3) Analogues and Their Stability to hCYP24A1-Dependent Catabolism
title_short Stereoselective Synthesis of 24-Fluoro-25-Hydroxyvitamin D(3) Analogues and Their Stability to hCYP24A1-Dependent Catabolism
title_sort stereoselective synthesis of 24-fluoro-25-hydroxyvitamin d(3) analogues and their stability to hcyp24a1-dependent catabolism
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8584271/
https://www.ncbi.nlm.nih.gov/pubmed/34769295
http://dx.doi.org/10.3390/ijms222111863
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