(23S,25R)-23,25,26-trihydroxyvitamin D₃ | 83198-41-8

• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 类固醇和类固醇衍生物
• 英文名称: (23S,25R)-23,25,26-trihydroxyvitamin D₃
• 英文别名: (23S,25R)-23,25,26-trihydroxycalciol；(2R,4S,6R)-6-[(1R,3aS,4E,7aR)-4-[(2Z)-2-[(5S)-5-hydroxy-2-methylidenecyclohexylidene]ethylidene]-7a-methyl-2,3,3a,5,6,7-hexahydro-1H-inden-1-yl]-2-methylheptane-1,2,4-triol
• CAS: 83198-41-8
• 化学式: C₂₇H₄₄O₄
• 分子量: 432.644
• InChiKey: GDIBDBUYVICGLY-CLKUJDLHSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4
• 重原子数：
  31
• 可旋转键数：
  7
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.78
• 拓扑面积：
  80.9
• 氢给体数：
  4
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  (23S,25R)-23,25,26-trihydroxyvitamin D₃ 在 adrenodoxin 、 乙二胺四乙酸 、 adrenodoxin reductase 、 recombinant CYP₂₄A₁ 、 还原型辅酶II(NADPH)四钠盐 作用下， 以 aq. buffer 为溶剂， 反应 0.5h， 生成 (23S,25R)-25-Hydroxyvitamin D3-26,23-lactone
  参考文献：
  名称：

  Elucidation of metabolic pathways of 25-hydroxyvitamin D3 mediated by CYP24A1 and CYP3A using Cyp24a1 knockout rats generated by CRISPR/Cas9 system

  摘要：

  CYP24A1-deficient (Cyp24a1 KO) rats were generated using the CRISPER/Cas9 system to investigate CYP24A1-dependent or -independent metabolism of 25(OH)D3, the prohormone of calcitriol. Plasma 25(OH)D3 concentrations in Cyp24a1 KO rats were approximately twofold higher than in wild-type rats. Wild-type rats showed five metabolites of 25(OH)D3 in plasma following oral administration of 25(OH)D3, and these metabolites were not detected in Cyp24a1 KO rats. Among these metabolites, 25(OH)D3-26,23-lactone was identified as the second major metabolite with a significantly higher Tmax value than others. When 23S,25(OH)2D3 was administered to Cyp24a1 KO rats, neither 23,25,26(OH)3D3 nor 25(OH)D3-26,23-lactone was observed. However, when 23S,25R,26(OH)3D3 was administered to Cyp24a1 KO rats, plasma 25(OH)D3-26,23-lactone was detected. These results suggested that CYP24A1 is responsible for the conversion of 25(OH)D3 to 23,25,26(OH)3D3 via 23,25(OH)2D3, but enzyme(s) other than CYP24A1 may be involved in the conversion of 23,25,26(OH)3D3 to 25(OH)D3-26,23-lactone. Enzymatic studies using recombinant human CYP species and the inhibitory effects of ketoconazole suggested that CYP3A plays an essential role in the conversion of 23,25,26(OH)3D3 into 25(OH)D3-26,23-lactone in both rats and humans. Taken together, our data indicate that Cyp24a1 KO rats are valuable for metabolic studies of vitamin D and its analogs. In addition, long-term administration of 25(OH)D3 to Cyp24a1 KO rats at 110 μg/kg body weight/day resulted in significant weight loss and ectopic calcification. Thus, Cyp24a1 KO rats could represent an important model for studying renal diseases originating from CYP24A1 dysfunction.

  DOI：

  10.1016/j.jbc.2021.100668
• 作为产物：
  描述：

  在 lithium aluminium tetrahydride 、 碘 、 三正丁基氢锡 作用下， 以 四氢呋喃 、 乙二醇二甲醚 、 氯仿 为溶剂， 反应 14.41h， 生成 (23S,25R)-23,25,26-trihydroxyvitamin D₃
  参考文献：
  名称：

  Stereoselective synthesis of (23S,25R)-23,25,26-trihydroxyvitamin D3 and (23S,25R)-25-hydroxyvitamin D3 26,23-lactol, presumed vitamin D3 metabolites

  摘要：

  DOI：

  10.1021/jo00145a033

文献信息

• Elucidation of metabolic pathways of 25-hydroxyvitamin D3 mediated by CYP24A1 and CYP3A using Cyp24a1 knockout rats generated by CRISPR/Cas9 system
  作者：Kaori Yasuda、Miyu Nishikawa、Kairi Okamoto、Kyohei Horibe、Hiroki Mano、Mana Yamaguchi、Risa Okon、Kimie Nakagawa、Naoko Tsugawa、Toshio Okano、Fumihiro Kawagoe、Atsushi Kittaka、Shinichi Ikushiro、Toshiyuki Sakaki

  DOI：10.1016/j.jbc.2021.100668

  日期：2021.1

  CYP24A1-deficient (Cyp24a1 KO) rats were generated using the CRISPER/Cas9 system to investigate CYP24A1-dependent or -independent metabolism of 25(OH)D3, the prohormone of calcitriol. Plasma 25(OH)D3 concentrations in Cyp24a1 KO rats were approximately twofold higher than in wild-type rats. Wild-type rats showed five metabolites of 25(OH)D3 in plasma following oral administration of 25(OH)D3, and these metabolites were not detected in Cyp24a1 KO rats. Among these metabolites, 25(OH)D3-26,23-lactone was identified as the second major metabolite with a significantly higher Tmax value than others. When 23S,25(OH)2D3 was administered to Cyp24a1 KO rats, neither 23,25,26(OH)3D3 nor 25(OH)D3-26,23-lactone was observed. However, when 23S,25R,26(OH)3D3 was administered to Cyp24a1 KO rats, plasma 25(OH)D3-26,23-lactone was detected. These results suggested that CYP24A1 is responsible for the conversion of 25(OH)D3 to 23,25,26(OH)3D3 via 23,25(OH)2D3, but enzyme(s) other than CYP24A1 may be involved in the conversion of 23,25,26(OH)3D3 to 25(OH)D3-26,23-lactone. Enzymatic studies using recombinant human CYP species and the inhibitory effects of ketoconazole suggested that CYP3A plays an essential role in the conversion of 23,25,26(OH)3D3 into 25(OH)D3-26,23-lactone in both rats and humans. Taken together, our data indicate that Cyp24a1 KO rats are valuable for metabolic studies of vitamin D and its analogs. In addition, long-term administration of 25(OH)D3 to Cyp24a1 KO rats at 110 μg/kg body weight/day resulted in significant weight loss and ectopic calcification. Thus, Cyp24a1 KO rats could represent an important model for studying renal diseases originating from CYP24A1 dysfunction.
• Stereoselective synthesis of (23S,25R)-23,25,26-trihydroxyvitamin D3 and (23S,25R)-25-hydroxyvitamin D3 26,23-lactol, presumed vitamin D3 metabolites
  作者：Sachiko Yamada、Keiko Nakayama、Hiroaki Takayama

  DOI：10.1021/jo00145a033

  日期：1982.11