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立体选择性合成 24-氟-25-羟基维生素 D 类似物及其对 hCYP24A1 依赖性代谢的稳定性。

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

机构信息

Faculty of Pharmaceutical Sciences, Teikyo University, 2-11-1 Kaga, Tokyo 173-8605, Japan.

Faculty of Engineering, Toyama Prefectural University, Imizu 939-0398, Japan.

出版信息

Int J Mol Sci. 2021 Nov 1;22(21):11863. doi: 10.3390/ijms222111863.

DOI:10.3390/ijms222111863
PMID:34769295
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8584271/
Abstract

Two 24-fluoro-25-hydroxyvitamin D analogues (,) were synthesized in a convergent manner. The introduction of a stereocenter to the vitamin D side-chain C24 position was achieved via Sharpless dihydroxylation, and a deoxyfluorination reaction was utilized for the fluorination step. Comparison between (24)- and (24)-24-fluoro-25-hydroxyvitamin D revealed that the C24--configuration isomer was more resistant to CYP24A1-dependent metabolism than its 24-isomer . The new synthetic route of the CYP24A1 main metabolite (24)-24,25-dihydroxyvitamin D () and its 24-isomer () was also studied using synthetic intermediates (,) in parallel.

摘要

两种 24-氟-25-羟基维生素 D 类似物（、）通过汇聚方式合成。通过 Sharpless 双羟化反应在维生素 D 侧链 C24 位置引入手性中心，并用脱氟氟化反应进行氟化步骤。（24）-和（24）-24-氟-25-羟基维生素 D 的比较表明，C24--构型异构体比其 24-异构体更能抵抗 CYP24A1 依赖性代谢。使用合成中间体（、）平行研究了 CYP24A1 主要代谢物（24）-24,25-二羟基维生素 D ()及其 24-异构体 ()的新合成途径。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/98c9/8584271/73c5ef39001b/ijms-22-11863-sch005.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/98c9/8584271/c5845761f108/ijms-22-11863-g002.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/98c9/8584271/73c5ef39001b/ijms-22-11863-sch005.jpg

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