(23S,25R)-25-Hydroxyvitamin D3-26,23-lactone | 77714-47-7

• 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)-25-Hydroxyvitamin D3-26,23-lactone
• 英文别名: (23S,25R)-calcidiol lactone；(23S,25R)-25-hyroxyvitamin D₃, 26,23-lactone；(23S,25R)-25-Hydroxycholecalciferol-26,23-lactone；(23S,25R)-25-hydroxyvitamin D3 26,23-lactone/(23S,25R)-25-hydroxycholecalciferol 26,23-lactone；(3R,5S)-5-[(2R)-2-[(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]propyl]-3-hydroxy-3-methyloxolan-2-one
• CAS: 77714-47-7
• 化学式: C₂₇H₄₀O₄
• 分子量: 428.612
• InChiKey: IJNDMZIDDKVXHR-PDGVZUSRSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5
• 重原子数：
  31
• 可旋转键数：
  4
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.74
• 拓扑面积：
  66.8
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  (23S,25R)-25-Hydroxyvitamin D3-26,23-lactone 在 二异丁基氢化铝 作用下， 以 正己烷 、 甲苯 为溶剂， 反应 2.0h， 以1.67 mg的产率得到(23S,25R)-25-hydroxyvitamin D₃ 26,23-lactol
  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
• 作为产物：
  描述：

  (23S,25R)-Cholesta-5,7-diene-3β,25-diol-26,23-lactone 生成 (23S,25R)-25-Hydroxyvitamin D3-26,23-lactone
  参考文献：
  名称：

  维生素D 3的代谢产物25-羟基胆钙化固醇26,23-内酯的结构与合成

  摘要：

  合成了维生素D 3的新代谢产物25-羟基胆钙化固醇26- 23-内酯的四种可能的立体异构体。我们确定了天然产物具有23 R和25 S的立体化学，并且它在促进肠道钙吸收方面具有维生素D 3活性的<1％。

  DOI：

  10.1039/c39810000424

文献信息

• Structure and synthesis of 25-hydroxycholecalciferol-26,23-lactone, a metabolite of vitamin D3
  作者：David S. Morris、Dudley H. Williams、Alan F. Norris

  DOI：10.1039/c39810000424

  日期：——

  The four possible stereoisomers of a new metabolite of vitamin D3, 25-hydroxycholecalciferol-26, 23-lactone, have been synthesised; we establish that the natural product has the 23R, 25S stereochemistry, and that it has <1% of the activity of vitamin D3 in bringing about intestinal calcium absorption.

  合成了维生素D 3的新代谢产物25-羟基胆钙化固醇26- 23-内酯的四种可能的立体异构体。我们确定了天然产物具有23 R和25 S的立体化学，并且它在促进肠道钙吸收方面具有维生素D 3活性的<1％。
• Stereoselective synthesis and structure proof of a metabolite of vitamin D3, (23S,25R)-25-hydroxyvitamin D3 26,23-lactone (calcidiol lactone).
  作者：SACHIKO YAMADA、KEIKO NAKAYAMA、HIROAKI TAKAYAMA

  DOI：10.1248/cpb.29.2393

  日期：——

  Stereochemical configurations of biologically prepared 25-hydroxyvitamin D3 26, 23-lactone (calcidiol lactone) at C-23 and C-25 are determined to be S and R, respectively, by comparison of its high performance LC retention time with those of (23S, 25R)-and (23R, 25S)-25-hydroxyvitamin D3 26, 23-lactone which have been synthesized stereoselectively starting from C-22 steroid aldehyde and (R)-or (S)-citramalic acid.

  生物制备的 25-羟基维生素 D3 26, 23-内酯（钙二醇内酯）在 C-23 和 C-25 上的立体化学构型分别被确定为 S 和 R、通过比较(23S, 25R)-25-hydroxyvitamin D3 26, 23-内酯和(23R, 25S)-25-hydroxyvitamin D3 26, 23-内酯与(23S, 25R)-(23R, 25S)-25-hydroxyvitamin D3 26, 23-内酯的高效液相色谱保留时间，可以确定它们在 C-23 和 C-25 的立体化学构型分别为 S 和 R。
• Structure and synthesis of 25-hydroxycholecalciferol-26,23-lactone, a metabolite of vitamin D
  作者：David S. Morris、Dudley H. Williams、Alan F. Norris

  DOI：10.1021/jo00330a007

  日期：1981.8
• 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.
• Eguchi, Tadashi; Takatsuto, Suguru; Hirano, Yutaka, Heterocycles, 1982, vol. 17, p. 359 - 375
  作者：Eguchi, Tadashi、Takatsuto, Suguru、Hirano, Yutaka、Ishiguro, Masaji、Ikekawa, Nobuo

  DOI：——

  日期：——