[2H]-Pre-1,25-D3 | 57102-09-7

• 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: [2H]-Pre-1,25-D3
• 英文别名: 1α,25-Dihydroxyprevitamin D₃；1α,25-dihydroxyprevitamin D3；1α,25-(OH)2-previtamin D3；1(S)25-dihydroxy previtamin D3；pre-calcitriol；1Alpha,25-Dihydroxyprevitamin D3；(1R,3S)-5-[(Z)-2-[(1R,3aR,7aR)-1-[(2R)-6-hydroxy-6-methylheptan-2-yl]-7a-methyl-1,2,3,3a,6,7-hexahydroinden-4-yl]ethenyl]-4-methylcyclohex-4-ene-1,3-diol
• CAS: 57102-09-7
• 化学式: C₂₇H₄₄O₃
• 分子量: 416.645
• InChiKey: DOIZGAFWGREMOD-MGCFMLCTSA-N

物化性质

• 熔点：
  >76°C (dec.)
• 沸点：
  564.5±50.0 °C(Predicted)
• 密度：
  1.119±0.06 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)：
  4.8
• 重原子数：
  30
• 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：
  60.7
• 氢给体数：
  3
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  [2H]-Pre-1,25-D3 反应 2.0h， 生成 骨化三醇
  参考文献：
  名称：

  有效合成1α，25-二羟基维生素D 3

  摘要：

  据报道，基于25-OH原维生素D 3（）的三唑啉Diels-Alder加合物的C-1功能化，可以有效合成标题化合物。

  DOI：

  10.1016/s0040-4020(01)83478-5
• 作为产物：
  描述：

  (1R,3aR,7aR)-1-[(1R)-1,5-二甲基-5-[(三乙基硅烷基)氧基]己基]八氢-7a-甲基-4H-茚-4-酮 在 Lindlar's catalyst 、 二乙酰二(三苯基膦)钯 喹啉 、 copper(l) iodide 、 正丁基锂 、 四丁基氟化铵 、 氢气 、 二乙胺 、 二异丙胺 作用下， 以 四氢呋喃 、 正己烷 、 乙酸乙酯 、 乙腈 、 正戊烷 为溶剂， 反应 265.75h， 生成 [2H]-Pre-1,25-D3
  参考文献：
  名称：

  CD环修饰反式十氢化萘1α，25-二羟基维生素D类似物的合成，生物学活性和构象分析。

  摘要：

  1,25-二羟基维生素D3（维生素D3的激素活性代谢物）的新型类似物系列，其特征在于存在转融合的十氢化萘CD-环系统，具有令人惊讶的生物学活性，并且在柔性部位具有特定的结构修饰与天然的氢化茚衍生物相比时 （1）在20个异构体的反式十氢化萘类似物之间观察到生物学活性差异很大，其规律与通常观察到的天然环大小相反。（2）在seco-B环区域修饰的几种反式十氢化萘类似物，包括维生素原衍生物，具有明显的维生素D样活性，而相应的氢化茚衍生物则没有活性。这种行为的分子起源仍在研究中。

  DOI：

  10.1039/b209147j

文献信息

• 14-Epi Stereoisomers of 25-Hydroxy- and 1.alpha.,25-Dihydroxyvitamin D3: Synthesis, Isomerization to Previtamins, and Biological Studies
  作者：David F. Maynard、William G. Trankle、Anthony W. Norman、William H. Okamura

  DOI：10.1021/jm00041a017

  日期：1994.7

  25-dihydroxyvitamin D3 (5), were synthesized, and their isomerization via [1,7]-sigmatropic hydrogen shifts to the corresponding previtamin forms (4' and 5', respectively) was studied. The activation parameters of the [1,7]-sigmatropic hydrogen shifts were found to be similar to those of other vitamin D analogues, although epimerization at C-14 shifts the equilibrium of the triene chromophore to the previtamin form

  合成了维生素D，14-epi-25-羟基维生素D3（4）和14-epi-1α，25-二羟基维生素D3（5）的C-14差向异构体，并通过[1,7]-σ异构化研究了氢转变为相应的维生素原形式（分别为4'和5'）。发现[1,7]-σ氢位移的活化参数与其他维生素D类似物的活化参数相似，尽管C-14的差向异构化将三烯生色团的平衡转变为维生素原形式。确定了小鸡中4、4'，5和5'引起肠道钙吸收和骨钙动员的体内生物活性。这些维生素D类似物是在C-14位置修饰的天然类固醇系列中的第一个，基本上没有活性。确定了在体外测定中得出的反映这些类似物结合小鸡肠核受体能力的相对竞争指数（RCI）。与天然配体1α，25-二羟基维生素D3（3）相比，类似物4、4'，5和5'的RCI值分别为0.08、0.01、15和1.6。 。因此，体内和体外数据有些差异，特别是对于5，其显着结合到小鸡肠受体。还进行了与人血清维生素D结合
• Versatile and Functionalised Intermediates for the Synthesis of Vitamin D and Novel Vitamin D Derivatives
  申请人：ENDOTHERM GMBH

  公开号：US20150344421A1

  公开（公告）日：2015-12-03

  Novel intermediates for the complete synthesis of vitamin D are provided that allow a great versatility of functional groups in the final vitamin derivatives. Vitamin derivatives that are epimeric in position 3 and vitamin derivatives with a wide range of functionalities in position 18, including compounds with isotopic labelling are provided.

  提供了用于完全合成维生素D的新型中间体，这些中间体允许在最终维生素衍生物中具有极大的功能性基团多样性。提供了在3号位置外消旋的维生素衍生物和在18号位置具有广泛功能性的维生素衍生物，包括具有同位素标记的化合物。
• VERSATILE AND FUNCTIONALISED INTERMEDIATES FOR THE SYNTHESIS OF VITAMIN D AND NOVEL VITAMIN D DERIVATIVES
  申请人：Endotherm GmbH

  公开号：EP2933246A1

  公开（公告）日：2015-10-21

  Versatile and functionalised intermediates for the synthesis of vitamin D and novel vitamin D derivatives. The invention provides novel intermediates for the complete synthesis of vitamin D and allows a great versatility of functional groups in the final vitamin derivatives. The invention also provides vitamin derivatives that are epimeric in position 3 and vitamin derivatives with a wide range of functionalities in position 18, including compounds with isotopic labeling

  用于合成维生素 D 和新型维生素 D 衍生物的多功能官能化中间体。本发明为维生素 D 的完全合成提供了新型中间体，并使最终维生素衍生物中的官能团具有极大的多样性。本发明还提供了在第 3 位上具有二聚体的维生素衍生物，以及在第 18 位上具有多种官能团的维生素衍生物，包括具有同位素标记的化合物。
• Studies of vitamin D (calciferol) and its analogs. 45. Studies on the A-ring diastereomers of 1.alpha.,25-dihydroxyvitamin D3
  作者：K. Raman Muralidharan、Angel R. De Lera、Shawn D. Isaeff、Anthony W. Norman、William H. Okamura

  DOI：10.1021/jo00059a048

  日期：1993.3

  The three A-ring diastereomers 3b (compound HL), 4a (compound HJ), and 4b (compound HH), of the steroid hormone 1alpha,25-dihydroxyvitamin D3 (1alpha,25-(OH)2-D3, 3a, compound C) have been synthesized and biologically evaluated. (R)-Carvone was converted in seven steps to the enantiomerically pure A-ring enyne 7a. Palladium-catalyzed cross-coupling of the latter with the CD-ring triflate 8 resulted in silyloxy dienyne 10, which was converted in three steps to 1beta,25-(OH)2-3-epi-D3 (4b). Oxidation of the latter with Dess-Martin reagent afforded trienone 6c, which upon reduction with sodium borohydride followed by thermolysis generated the 1alpha-epimer 4a. An identical sequence converted 1alpha,25-(OH)2-D3 to its 1beta-epimer 3b via trienone 5c. Reduction of the latter with sodium triacetoxyborohydride followed by thermal isomerization regenerated the hormone 3a. Relative competitive indices (RCls) of these analogues, which reflect their ability to bind to the chick intestinal nuclear receptor under in vitro conditions, were determined. Analogues 3b, 4a, and 4b had RCI values of 0.8 +/- 0.1 %, 24.0 +/- 4.5 %, and 0.22 +/- 0.01 %, respectively, in comparison to 1alpha,25-(OH)2-D3 whose value is 100% by definition. In addition, in vivo biological evaluation of these analogues was performed to determine their ability to induce intestinal calcium absorption (ICA) and bone calcium mobilization (BCM) in vitamin D deficient chicks. Analogue 4a was effective in stimulating ICA and BCM whereas analogues 3b and 4b exhibited little potency in eliciting these biological effects.
• Vitamin D (calciferol) and its analogs. 40. 1.alpha.,25-Dihydroxyprevitamin D3: synthesis of the 9,14,19,19,19-pentadeuterio derivative and a kinetic study of its [1,7]-sigmatropic shift to 1.alpha.,25-dihydroxyvitamin D3
  作者：Michael L. Curtin、William H. Okamura

  DOI：10.1021/ja00018a038

  日期：1991.8

  The hormonally active steroid 1-alpha, 25-dihydroxyvitamin D3 (3) exists in equilibrium with its previtamin form 5. In an attempt to further understand the significance of this previtamin and previtamin D's in general, the pentadeuterio analogue of 5 was synthesized. Accordingly, 9, 14, 19, 19, 19-pentadeuterio-1-alpha, 25-dihydroxyprevitamin D3 (6) was prepared from the readily available, optically active synthons (S)-(+)-carvone (10) and the Inhoffen-Lythgoe diol (9). A general method was developed to regioselectively deuteriate beta-methyl-alpha,beta-unsaturated aldehydes via their Schiff bases and was used in the synthesis to convert aldehyde 16a to its deuteriated analogue 16b. Thermolysis of 6 afforded 9, 9, 14, 19, 19-pentadeuterio-1-alpha,25-dihydroxyvitamin D3 (24). A kinetic investigation of the [1, 7]-sigmatropic hydrogen (deuterium) shifts which convert previtams 5 and 6 to vitamins 3 and 24, respectively, revealed that at 25-degrees-C the process proceeds with a relatively normal primary kinetic isotope effect, k(H)/k(D), of 5.5.