表骨化三醇 | 66791-71-7

• 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
• 中文名称: 表骨化三醇
• 英文名称: 1,25-Dihydroxyvitamin D3
• 英文别名: 1α,25-dihydroxyvitamin D₃；1α,25-dihydroxyvitamin D3；1,25(OH)₂D₃；BML-DM200-0050；1beta-Calcitriol；(1R,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-1,3-diol
• CAS: 66791-71-7
• 化学式: C₂₇H₄₄O₃
• 分子量: 416.645
• InChiKey: GMRQFYUYWCNGIN-PEJFXWBPSA-N

物化性质

• 沸点：
  565.0±50.0 °C(Predicted)
• 密度：
  1.06±0.1 g/cm3(Predicted)
• 溶解度：
  可溶于氯仿（少许）、甲醇（少许）

计算性质

• 辛醇/水分配系数(LogP)：
  5.1
• 重原子数：
  30
• 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：
  60.7
• 氢给体数：
  3
• 氢受体数：
  3

制备方法与用途

生物活性方面，Impurity B of Calcitriol 是 Calcitriol 的一种杂质。Calcitriol 是维生素 D3 的活性代谢物，能够激活维生素 D 受体。

反应信息

• 作为反应物：
  描述：

  表骨化三醇 生成 1α-Hydroxy-25-fluorvitamin D(3)
  参考文献：
  名称：

  The synthesis and activity in vitro of 25-masked-1α-hydroxylated vitamin D3 analogs

  摘要：

  1alphaHydroxylated-25-masked-vitamin D3 and analogs were synthesized as probes to help evaluate the role of 25-hydroxyl group in hormone-receptor interactions of 1alpha,25-dihydroxyvitamin D3 (13a). Synthetic work on model systems showed that the steroidal 25-hydroxyl group could be easily fluorinated in high yield with diethylaminosulfur trifluoride. Treatment of 25-fluoro compound with acetic acid resulted in both elimination and displacement of fluorine by acetate. The desired 1alpha-hydroxy-25-fluoro-vitamin D3 (14b) was obtained efficiently by fluorination and subsequent deacetylation of 1alpha,25-dihydroxyvitamin D3 1,3-diacetate (13b). Also obtained was a mixture of 1alpha-hydroxyvitamin D3-24- and 25-enes (15b). Both 14b and 15b were 300-400 times less active than 13a in the chick intestinal cytosol protein binding assay, making these analogs similar in potency to 1alpha-hydroxyvitamin D3 in vitro. The essentially equivalent activity of 14b and 15b with 1alpha-hydroxyvitamin D3 indicates that in the absence of a 25-hydroxyl group some alterations to the side chain carbons of 13a may be tolerated without further weakening analog-protein interactions. The fluoroanalog 14b was also about 250 times less potent than 13a in stimulating bone resorption in vitro. These compounds should prove to be valuable tools in aiding understanding of the salient structural features of the vitamin D3 metabolites.

  DOI：

  10.1016/0039-128x(78)90058-2
• 作为产物：
  描述：

  (3R,5R)-oct-1-en-7-yn-3,5-diol 在 2,6-二甲基吡啶 、 tris-(dibenzylideneacetone)dipalladium(0) 、 camphor-10-sulfonic acid 、 三乙胺 、 三苯基膦 作用下， 以 甲醇 、 二氯甲烷 、 甲苯 为溶剂， 反应 6.0h， 生成 表骨化三醇
  参考文献：
  名称：

  一种新颖实用的途径，用于1个α，25-二羟基维生素D3类似物的A环烯炔合子：1个α，25-二羟基维生素D2和3-甲基-1,25-二羟基维生素D3的A环非对映异构体的合成。

  摘要：

  开发了一种新颖而实用的通往A环烯炔合子（2）的途径，该途径可用于多种1α，25-二羟基维生素D3（1）的A环类似物。这种新方法改进了1的A环非对映异构体，化合物13-15的合成，以及新的类似物2-甲基-1,25-二羟基维生素D3（4）及其所有可能的非对映异构体的合成。对2-甲基类似物的生物学评估表明，α-α-β-异构体的效力比1。

  DOI：

  10.1016/s0960-894x(97)10204-9

文献信息

• Efficient synthesis and biological evaluation of all a-ring diastereomers of 1α,25-dihydroxyvitamin D3 and its 20-epimer
  作者：Toshie Fujishima、Katsuhiro Konno、Kimie Nakagawa、Mayuko Kurobe、Toshio Okano、Hiroaki Takayama

  DOI：10.1016/s0968-0896(99)00262-x

  日期：2000.1

  An improved synthesis of the diastereomers of 1alpha,25-dihydroxyvitamin D3 (1) was accomplished utilizing our practical route to the A-ring synthon. We applied this procedure to synthesize for the first time all possible A-ring diastereomers of 20-epi-1alpha,25-dihydroxyvitamin D3 (2). Ten-step conversion of 1-(4-methoxyphenoxy)but-3-ene (6), including enantiomeric introduction of the C-3 hydroxyl

  利用我们通往A环合成子的实用途径，完成了1α，25-二羟基维生素D3（1）非对映异构体的合成。我们应用此程序首次合成了20-epi-1alpha，25-dihydroxyvitamin D3（2）的所有可能的A环非对映异构体。1-（4-甲氧基苯氧基）丁-3-烯（6）的十步转化，包括通过Sharpless不对称二羟基化将C-3羟基对映体引入烯烃，提供了A环烯炔的所有四种可能的立体异构体（3）。即（3R，5R）-，（3R，5S）-，（3S，5R）-和（3S，5S）-双[（叔丁基二甲基甲硅烷基）氧基] oct-1-en-7-yne总产量。钯催化的A环合成子与20-epi CD环部分的交叉偶联（5），（E）-（20S）-de-A，B-8-（溴亚甲基）胆甾醇25-ol，然后解除保护，提供了必需的20-epi-1alpha，25-二羟基维生素D3非对映异构体（2）。根据对维生素D受体（VDR）和维生素
• Plasminogen Activator Inhibitor-1 Inhibitors and Methods of Use Thereof to Modulate Lipid Metabolism
  申请人：Lawrence Daniel A.

  公开号：US20100137194A1

  公开（公告）日：2010-06-03

  The invention relates to plasminogen activator-1 (PAI-1) inhibitor compounds and uses thereof in the treatment of any disease or condition associated with elevated PAI-1. The invention includes, but is not limited to, the use of such compounds to modulate lipid metabolism and treat conditions associated with elevated PAI-1, cholesterol, or lipid levels.

  本发明涉及纤溶酶原激活剂-1（PAI-1）抑制剂化合物及其在治疗任何与升高的PAI-1相关的疾病或病状中的应用。本发明包括但不限于使用这些化合物来调节脂质代谢并治疗与升高的PAI-1、胆固醇或脂质水平相关的病症。
• 1-Hydroxyvitamin D derivatives
  申请人：NISSHIN FLOUR MILLING CO., LTD.

  公开号：EP0506388A1

  公开（公告）日：1992-09-30

  1-Hydroxyvitamin D esters of vitamin A acid are useful for preventing and treating osteoporosis, cutaneous ulcer and tumour.

  维生素 A 酸的 1-羟基维生素 D 酯可用于预防和治疗骨质疏松症、皮肤溃疡和肿瘤。
• Characterization of rat and human CYP2J enzymes as Vitamin D 25-hydroxylases
  作者：Isamu Aiba、Tomoaki Yamasaki、Toshimasa Shinki、Shunsuke Izumi、Keiko Yamamoto、Sachiko Yamada、Hiroaki Terato、Hiroshi Ide、Yoshihiko Ohyama

  DOI：10.1016/j.steroids.2006.04.009

  日期：2006.10

  Vitamin D is 25-hydroxylated in the liver, before being activated by 1 alpha-hydroxylation in the kidney. Recently, the rat cytochrome P450 2J3 (CYP2J3) has been identified as a principal vitamin D 25-hydroxylase in the rat [Yamasaki T, Izumi S, Ide H, Ohyama Y Identification of a novel rat microsomal vitamin D-3 25-hydroxylase. J Biol Chem 2004;279(22):22848-56]. In this study, we examine whether human CYP2J2 that exhibits 73% amino acid homology to rat CYP2J3 has similar catalytic properties. Recombinant human CYP2J2 was overexpressed in Escherichia coli, purified, and assayed for vitamin D 25-hydroxylation activity. We found significant 25-hydroxylation activity toward vitamin D-3 (turnover number, 0.087 min(-1)), vitamin D-2 (0.16 min(-1)), and 1 alpha-hydroxyvitamin D-3 (2.2 min(-1)). Interestingly, human CYP2J2 hydroxylated vitamin D-2, an exogenous vitamin D, at a higher rate than it did vitamin D-3, an endogenous vitamin D, whereas, rat CYP2J3 hydroxylated vitamin D-3 (1.4 min(-1)) more efficiently than vitamin D-2 (0.86 min(-1)). Our study demonstrated that human CYP2J2 exhibits 25-hydroxylation activity as well as rat CYP2J3, although the activity of human CYP2J2 is weaker than rat CYP2J3. CYP2J2 and CYP2J3 exhibit distinct preferences toward vitamin D-3 and D-2. (c) 2006 Elsevier Inc. All rights reserved.
• New Convergent Synthesis of 1α,25-Dihydroxyvitamin D₃ and Its Analogues by Suzuki−Miyaura Coupling between A-Ring and C,D-Ring Parts
  作者：Takeshi Hanazawa、Akiko Koyama、Kunio Nakata、Sentaro Okamoto、Fumie Sato

  DOI：10.1021/jo0353435

  日期：2003.12.1

  A new convergent method for the synthesis of 1alpha,25-dihydroxyvitamin D-3 and its analogues has been developed that involves efficient preparation of the A-ring part la, (Z)-(3S,5R)-1-bromomethylene-3,5-bis(tert-butyldimethylsilyloxy)-2-methylenecyclohexane, starting from epichlorohydrin (4) and its Suzuki-Miyaura coupling reaction with the C,D-ring part 12. Thus, (R)-4 was converted to (3S,5R)-5-(tert-butyldimethylsilyloxy)-8-(trimethylsilyl)-oct-1-en-7-yn-3-ol (3a) through a ten-step reaction sequence in 49% overall yield. Compound 3a thus obtained was treated with a Ti(O-i-Pr)(4)/2 i-PrMgCl reagent and then with NBS to afford (Z)-(1S,2S,5R)-2-bromomethyl-3-[bromo(trimethylsilyl)methylene]-5-(tert-butyldimethylsilyloxy)cyclohexanol (10a) in 51% yield, from which la was obtained in 87% yield by sequential treatment with TBSCl/imidazole, DBU, and Cs2CO3. The resulting A-ring intermediate la was reacted with alkenylboronate 12 in the presence of a PdCl2(dppf) catalyst to furnish 1alpha,25-dihydroxyvitamin D-3 in 82% yield after protodesilylation. Similarly, all of the other three possible stereoisomers of A-ring parts 1b, 1c, and 1d were prepared, from which 1-epi-, 3-epi-, and 1,3-di-epi-1alpha,25-dihydroxyvitamin D-3 were synthesized by coupling with 12 in excellent yield, respectively. Starting from la and 1c, des-C,D-I(x,25-dihydroxyvitamin D-3 analogues, retiferol 13 and its 3-epi derivative, were also prepared, respectively.