(1β,2α,3α,5Z,7E,20R)-9,10-secocholesta-5,7,10(19)-triene-1,2,3,25-tetrol

• 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: (1β,2α,3α,5Z,7E,20R)-9,10-secocholesta-5,7,10(19)-triene-1,2,3,25-tetrol
• 英文别名: 1α,2β,3β,25-tetrahydroxy-9.10-secocholesta-5,7,10(19)-triene；1α,2β,25(OH)₃D₃；1alpha,2beta,25-trihydroxy vitamin D3；(1R,2R,3R,5Z)-5-[(2E)-2-[(1R,3aS,7aR)-1-[(2R)-6-hydroxy-6-methylheptan-2-yl]-7a-methyl-2,3,3a,5,6,7-hexahydro-1H-inden-4-ylidene]ethylidene]-4-methylidenecyclohexane-1,2,3-triol
• 化学式: C₂₇H₄₄O₄
• 分子量: 432.644
• InChiKey: JGIYYEHLYUOKSD-FQKVRLMOSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.1
• 重原子数：
  31
• 可旋转键数：
  6
• 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

• 作为产物：
  描述：

  (1R,3aR,7aR)-1-{(1R)-1,5-dimethyl-5-[(trimethylsilyl)oxy]hexyl}-7a-methyloctahydro-4H-inden-4-one 在 四(三苯基膦)钯 四丁基氟化铵 、 sodium hexamethyldisilazane 、 三乙胺 作用下， 以 四氢呋喃 、 甲苯 为溶剂， 反应 2.0h， 生成 (1β,2α,3α,5Z,7E,20R)-9,10-secocholesta-5,7,10(19)-triene-1,2,3,25-tetrol
  参考文献：
  名称：

  Synthesis of putative metabolites of 1α,25-dihydroxy-2β-(3-hydroxypropoxy)vitamin D3 (ED-71)

  摘要：

  1 alpha,25-Dihydroxy-2 beta-(3-hydroxypropoxy)vitamin D-3 (ED-71), an analog of active vitamin D-3, 1 alpha,25-dihydroxyvitamin D-3 [1,25(OH)(2)D-3] is under phase III clinical trials in Japan for the treatment of osteoporosis and bone fracture prevention. Since ED-71 has a substituent at the 2 beta-position of the A-ring, it is recognized that the metabolic pathway of ED-71 might be more complicated than 1,25(OH)(2)D-3 because of metabolism at the 2 beta-position substituent in addition to the inherent metabolism of the side chain. To clarify the metabolism of hydroxypropoxy substituent of the 2 beta-positon and a combination of metabolism between side chain and 2 beta-positon, four putative metabolites of ED-71 have been prepared as authentic samples. The metabolites at the 2 beta-positon, the methyl ester derivative considered as an ester standard of the oxidized metabolite and the tetraol derivative as the truncated metabolite were synthesized from alpha-epoxide, a key intermediate of ED-71 synthesis. The combination metabolites between side chain and 2 beta-positon, the 24(S)- and 24(R)-pentaols were synthesized using Trost's convergent method. (c) 2006 Elsevier Inc. All rights reserved.

  DOI：

  10.1016/j.steroids.2005.11.001

文献信息

• Parallel Synthesis of a Vitamin D₃ Library in the Solid-Phase
  作者：Ichiro Hijikuro、Takayuki Doi、Takashi Takahashi

  DOI：10.1021/ja003976k

  日期：2001.4.1

  introduction of the side chain and cleavage from resin with a Cu(I)-catalyzed Grignard reagent. Parallel synthesis of the vitamin D(3) analogues was accomplished by a split and pool methodology utilizing radio frequency encoded combinatorial chemistry, and a manual parallel synthesizer for side chain diversification and deprotection. Additionally, we demonstrated the synthesis of various A-rings in a similar

  描述了在固体支持物上高效合成维生素 D(3) 系统。开发了两种用于固相合成维生素 D(3) 的合成策略。一种用于 11-羟基类似物，另一种用于大多数其他合成类似物。在后一种策略中，磺酸盐连接的 CD 环 58 最初固定在 PS-DES 树脂上，得到固体负载的 CD 环 63（方案 10）。类似地，通过将​​ CD 环 10 连接到氯磺酸树脂 64 上来制备固体负载的 CD 环 63。维生素 D(3) 系统是通过 A 环氧化膦的 Horner-Wadsworth-Emmons 反应合成的固体支持的 CD 环，然后同时引入侧链并用 Cu(I) 催化的格氏试剂从树脂上裂解。维生素 D(3) 类似物的并行合成是通过使用射频编码组合化学的拆分和池方法以及用于侧链多样化和脱保护的手动并行合成器来完成的。此外，我们展示了在类似的协议中合成各种 A 环，以有效地制备积木。
• Human hepatic metabolism of the anti‐osteoporosis drug eldecalcitol involves sterol C4‐methyl oxidase
  作者：Kaori Yasuda、Yuasa Iwanaga、Kazuaki Ogawa、Hiroki Mano、Sera Ueno、Shutaro Kimoto、Miho Ohta、Masaki Kamakura、Shinichi Ikushiro、Toshiyuki Sakaki

  DOI：10.1002/prp2.120

  日期：2015.3

  the activity in human liver microsomes by only 36%, suggesting that other enzymes could be involved in ED-71 metabolism. Because metabolism was dramatically inhibited by cyanide, we assumed that sterol C4-methyl oxidase like gene product (SC4MOL) might contribute to the metabolism of ED-71. It is noted that SC4MOL is physiologically essential for cholesterol synthesis. Recombinant human SC4MOL expressed

  使用体外系统研究了维生素D3活性形式的2β-羟基丙氧基化类似物Eldecalcitol（ED-71）的代谢。ED-71在人小肠和肝微粒体内代谢为1α，2β，25-三羟基维生素D3（1α，2β，25（OH）3D3）。为了鉴定参与该代谢的酶，我们通过属于CYP1、2和3家族的重组P450亚型检查了NADPH依赖性代谢，并揭示了CYP3A4具有这种活性。但是，CYP3A4特异性抑制剂酮康唑使人肝微粒体的活性仅降低36％，表明其他酶可能参与ED-71代谢。因为新陈代谢被氰化物显着抑制，所以我们认为固醇C4-甲基氧化酶样基因产物（SC4MOL）可能有助于ED-71的新陈代谢。应当指出，SC4MOL对于胆固醇合成是生理必需的。在COS7，酿酒酵母或大肠杆菌细胞中表达的重组人SC4MOL将ED-71转化为1α，2β，25（OH）3D3。此外，我们评估了重组CYP24A1对ED-71的代谢，该CYP24A
• Synthesis of putative metabolites of 1α,25-dihydroxy-2β-(3-hydroxypropoxy)vitamin D3 (ED-71)
  作者：Yoshiyuki Ono、Hiroyoshi Watanabe、Ikuo Taira、Keisuke Takahashi、Jun Ishihara、Susumi Hatakeyama、Noboru Kubodera

  DOI：10.1016/j.steroids.2005.11.001

  日期：2006.7

  1 alpha,25-Dihydroxy-2 beta-(3-hydroxypropoxy)vitamin D-3 (ED-71), an analog of active vitamin D-3, 1 alpha,25-dihydroxyvitamin D-3 [1,25(OH)(2)D-3] is under phase III clinical trials in Japan for the treatment of osteoporosis and bone fracture prevention. Since ED-71 has a substituent at the 2 beta-position of the A-ring, it is recognized that the metabolic pathway of ED-71 might be more complicated than 1,25(OH)(2)D-3 because of metabolism at the 2 beta-position substituent in addition to the inherent metabolism of the side chain. To clarify the metabolism of hydroxypropoxy substituent of the 2 beta-positon and a combination of metabolism between side chain and 2 beta-positon, four putative metabolites of ED-71 have been prepared as authentic samples. The metabolites at the 2 beta-positon, the methyl ester derivative considered as an ester standard of the oxidized metabolite and the tetraol derivative as the truncated metabolite were synthesized from alpha-epoxide, a key intermediate of ED-71 synthesis. The combination metabolites between side chain and 2 beta-positon, the 24(S)- and 24(R)-pentaols were synthesized using Trost's convergent method. (c) 2006 Elsevier Inc. All rights reserved.