(8S,20S)-des-A,B-20-(cyanomethyl)-8β-[(triethylsilyl)oxy]pregnane | 1335097-25-0

• 分子结构分类: 有机化合物 - 有机金属化合物 - 有机类金属化合物
• 英文名称: (8S,20S)-des-A,B-20-(cyanomethyl)-8β-[(triethylsilyl)oxy]pregnane
• 英文别名: (8S,20S)-des-A,B-8-[(triethylsilyl)oxy]-20-(cyanomethyl)pregnane；(3S)-3-[(1R,3aR,4S,7aR)-7a-methyl-4-triethylsilyloxy-1,2,3,3a,4,5,6,7-octahydroinden-1-yl]butanenitrile
• CAS: 1335097-25-0
• 化学式: C₂₀H₃₇NOSi
• 分子量: 335.605
• InChiKey: HAHIWTWHPXVQKI-LJDSDSDDSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.14
• 重原子数：
  23
• 可旋转键数：
  7
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.95
• 拓扑面积：
  33
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  (8S,20S)-des-A,B-20-(cyanomethyl)-8β-[(triethylsilyl)oxy]pregnane 在 palladium 10% on activated carbon 正丁基锂 、 氢气 、 二异丁基氢化铝 、 二异丙胺 作用下， 以 四氢呋喃 、 甲醇 、 乙醚 、 正己烷 、 二氯甲烷 为溶剂， 反应 66.0h， 生成 (8S,20R)-des-A,B-22,22-dimethyl-cholestane-8β,25-diol
  参考文献：
  名称：

  (20S)-2-METHYLENE-19-NOR-22-DIMETHYL-1alpha,25-DIHYDROXYVITAMIN D3 AND (20R)-2-METHYLENE-19-NOR-22-DIMETHYL-1alpha,25-HYDROXYVITAMIN D3

  摘要：

  提供了具有公式I的化合物，其中X1、X2和X3分别选择自H或羟基保护基团。这些化合物可用于制备药物组合物，并可用于治疗各种生物条件。

  公开号：

  US20110237556A1
• 作为产物：
  描述：

  (S)-2-((3R,3aR,7S,7aR)-octahydro-7-hydroxy-3a-methyl-1H-inden-3-yl)propyl 4-methylbenzenesulfonate 在 吡啶 、 2,6-二甲基吡啶 、 sodium tetrahydroborate 、 四丁基氢氧化铵 、 碳酸氢钠 、 二甲基亚砜 作用下， 以 乙醇 、 二氯甲烷 、 水 、 二甲基亚砜 为溶剂， 反应 24.25h， 生成 (8S,20S)-des-A,B-20-(cyanomethyl)-8β-[(triethylsilyl)oxy]pregnane
  参考文献：
  名称：

  (20S)-2-METHYLENE-19-NOR-22-DIMETHYL-1alpha,25-DIHYDROXYVITAMIN D3 AND (20R)-2-METHYLENE-19-NOR-22-DIMETHYL-1alpha,25-HYDROXYVITAMIN D3

  摘要：

  提供了具有公式I的化合物，其中X1、X2和X3分别选择自H或羟基保护基团。这些化合物可用于制备药物组合物，并可用于治疗各种生物条件。

  公开号：

  US20110237556A1

文献信息

• DIASTEREOMERS OF 2-METHYLENE-19-NOR-22-METHYL-1ALPHA,25-DIHYDROXYVITAMIN D3
  申请人：DeLuca Hector F.

  公开号：US20110237557A1

  公开（公告）日：2011-09-29

  Compounds of formula I are provided where X 1 , X 2 , and X 3 are independently selected from H or hydroxy protecting groups. Such compounds may be used in preparing pharmaceutical compositions and are useful in treating a variety of biological conditions.

  提供了公式I的化合物，其中X1、X2和X3分别选自H或羟基保护基团。这些化合物可用于制备药物组合物，并可用于治疗各种生物状况。
• A 20<i>S</i> Combined with a 22<i>R</i> Configuration Markedly Increases both in Vivo and in Vitro Biological Activity of 1α,25-Dihydroxy-22-methyl-2-methylene-19-norvitamin D₃
  作者：Agnieszka Flores、Rafal R. Sicinski、Pawel Grzywacz、James B. Thoden、Lori A. Plum、Margaret Clagett-Dame、Hector F. DeLuca

  DOI：10.1021/jm300187x

  日期：2012.5.10

  Six new analogues of 1 alpha,25-dihydroxy-19-norvitamin D-3 (3a-4b, 5, and 6) were prepared by a convergent synthesis applying the Wittig-Horner reaction as a key step. The influence of methyl groups at C-22 on their biological activity was examined. It was established that both in vitro and in vivo activity is strongly dependent on the configuration of the stereogenic centers at C-20 and C-22. Introduction of the second methyl group at C-22 (analogues 5 and 6) generates the compounds that are slightly more potent than 1 alpha,25-(OH)(2)D-3 in the in vitro tests but much less potent in vivo. The greatest in vitro and in vivo biological activity was achieved when the C-20 is in the S configuration and the C-22 is in the R configuration. The building blocks for the synthesis, the respective (20R,22R)-, (20R,22S)-, (20S,22R)-, and (20S,22S)-diols, were obtained by fractional crystallization of mixtures of the corresponding diastereomers. Structures and absolute configurations of the diols 21a, 21b, and 22a as well as analogues 3a, 5, and 6 were confirmed by the X-ray crystallography.
• A Methylene Group on C-2 of 24,24-Difluoro-19-nor-1α,25-dihydroxyvitamin D₃ Markedly Increases Bone Calcium Mobilization in Vivo
  作者：Agnieszka Flores、Ilaria Massarelli、James B. Thoden、Lori A. Plum、Hector F. DeLuca

  DOI：10.1021/acs.jmedchem.5b01564

  日期：2015.12.24

  Four side chain fluorinated analogues of 1 alpha,25-dihydroxy-19-norvitamin D have been prepared in convergent syntheses using the Wittig-Homer reaction as a key step. Structures and absolute configurations of analogues 3 and 5 were confirmed by X-ray crystallography. All analogues showed high potency in HL-60 cell differentiation and vitamin D-24-hydroxylase (24-OHase) transcription as compared to 1 alpha,25-dihydroxyvitamin D-3 (1). Most important is that all of the 20S-configured derivatives (4 and 6) had high bone mobilizing activity in vivo. However, in the 20R series, a 2-methylene group was required for high bone mobilizing activity. A change in positioning of the 20R molecule in the vitamin D receptor when the 2-methylene group is present may provide new insight into the molecular basis of bone calcium mobilization induced by vitamin D.