[(1S,3R)-3-[(tert-butyldimethylsilyl)oxy]-1-hydroxy-4-methylene]cyclohexanecarboxylic acid methyl ester | 1246364-46-4

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: [(1S,3R)-3-[(tert-butyldimethylsilyl)oxy]-1-hydroxy-4-methylene]cyclohexanecarboxylic acid methyl ester
• 英文别名: methyl (1S,3R)-3-[tert-butyl(dimethyl)silyl]oxy-1-hydroxy-4-methylidenecyclohexane-1-carboxylate
• CAS: 1246364-46-4
• 化学式: C₁₅H₂₈O₄Si
• 分子量: 300.47
• InChiKey: QHFLXTIGUONNCT-DOMZBBRYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.02
• 重原子数：
  20
• 可旋转键数：
  5
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.8
• 拓扑面积：
  55.8
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  [(1S,3R)-3-[(tert-butyldimethylsilyl)oxy]-1-hydroxy-4-methylene]cyclohexanecarboxylic acid methyl ester 在 sodium periodate 、 二异丁基氢化铝 作用下， 以 甲醇 、 二氯甲烷 、 水 为溶剂， 反应 4.0h， 生成 (R)-3-[(tert-butyldimethylsilyl)oxy]-4-methylene-cyclohexanone
  参考文献：
  名称：

  1-Desoxy-2-Methylene-19-Nor-Vitamin D Analogs and Their Uses

  摘要：

  这项发明揭示了1-去氧-2-亚甲基-19-去氧维生素D类似物，具体包括(20S)-25-羟基-1-去氧-2-亚甲基-19-去氧维生素D3及其药用。这种化合物表现出相对较高的结合活性，并在阻止未分化细胞的增殖并诱导它们分化为单核细胞方面具有显著活性，因此显示出作为抗癌剂的用途，特别是用于治疗或预防白血病、结肠癌、乳腺癌、皮肤癌或前列腺癌。

  公开号：

  US20110082121A1
• 作为产物：
  描述：

  quinic acid 在 重铬酸吡啶 、 偶氮二异丁腈 、 potassium tert-butylate 、 三正丁基氢锡 、 对甲苯磺酸 作用下， 以 四氢呋喃 、 N,N-二甲基甲酰胺 、 甲苯 、 乙腈 、 苯 为溶剂， 反应 98.0h， 生成 [(1S,3R)-3-[(tert-butyldimethylsilyl)oxy]-1-hydroxy-4-methylene]cyclohexanecarboxylic acid methyl ester
  参考文献：
  名称：

  1-Desoxy-2-Methylene-19-Nor-Vitamin D Analogs and Their Uses

  摘要：

  这项发明揭示了1-去氧-2-亚甲基-19-去氧维生素D类似物，具体包括(20S)-25-羟基-1-去氧-2-亚甲基-19-去氧维生素D3及其药用。这种化合物表现出相对较高的结合活性，并在阻止未分化细胞的增殖并诱导它们分化为单核细胞方面具有显著活性，因此显示出作为抗癌剂的用途，特别是用于治疗或预防白血病、结肠癌、乳腺癌、皮肤癌或前列腺癌。

  公开号：

  US20110082121A1

文献信息

• 2-METHYLENE-VITAMIN D ANALOGS AND THEIR USES
  申请人：WISCONSIN ALUMNI RESEARCH FOUNDATION

  公开号：US20130102573A1

  公开（公告）日：2013-04-25

  This invention discloses 2-methylene-vitamin D analogs, and specifically (20S)-25-hydroxy-2-methylene-vitamin D 3 and (20R)-25-hydroxy-2-methylene-vitamin D 3 , as well as pharmaceutical uses therefor. These compounds exhibit relatively high binding activity and pronounced activity in arresting the proliferation of undifferentiated cells and inducing their differentiation to the monocyte thus evidencing use as an anti-cancer agent especially for the treatment or prevention of osteosarcoma, leukemia, colon cancer, breast cancer, skin cancer or prostate cancer. These compounds also have relatively high calcemic activities evidencing use in the treatment of bone diseases.

  本发明公开了2-亚甲基-维生素D类似物，特别是(20S)-25-羟基-2-亚甲基-维生素D3和(20R)-25-羟基-2-亚甲基-维生素D3，以及它们的药物用途。这些化合物具有相对较高的结合活性和显著的抑制未分化细胞增殖并诱导其向单核细胞分化的活性，因此可用作抗癌剂，特别用于治疗或预防骨肉瘤、白血病、结肠癌、乳腺癌、皮肤癌或前列腺癌。这些化合物还具有相对较高的升高血钙作用，表明可用于治疗骨骼疾病。
• Synthesis and Biological Activity of 25-Hydroxy-2-methylene-vitamin D₃ Analogues Monohydroxylated in the A-ring
  作者：Izabela K. Sibilska、Rafal R. Sicinski、Justin T. Ochalek、Lori A. Plum、Hector F. DeLuca

  DOI：10.1021/jm500750b

  日期：2014.10.23

  The 20R- and 20S-isomers of 25-hydroxy-2-methylene-vitamin D3 and 3-desoxy-1α,25-dihydroxy-2-methylene-vitamin D3 have been synthesized. Two alternative synthetic routes were devised for preparation of the required A-ring synthons, starting from the chiral compound derived from the (−)-quinic acid and, alternatively, from the commercially available achiral precursor, monoprotected 1,4-cyclohexanedione

  合成了25-羟基-2-亚甲基维生素D 3和3-脱氧-1α，25-二羟基-2-亚甲基维生素D 3的20 R-和20 S-异构体。从衍生自（-）-奎尼酸的手性化合物以及可商购的非手性前体单保护的1,4-环己二酮开始，设计了两种替代的合成路线来制备所需的A环合成子。A环dienynes是由园头过程加上相应的C，d-环片段，从受保护的（20衍生的烯醇三氟甲磺酸酯[R ） -或（20小号）-25-羟基格伦德曼酮。所有四种化合物在体内均具有重要的作用活性对骨钙动员和肠道钙运输的影响。2-亚甲基的存在提高了所有四个类似物的肠钙转运活性，高于天然激素1α，25-二羟基维生素D 3的肠钙转运活性。与此相反，动员骨钙是等于由1α，25-二羟基维生素d产生3具有（20种化合物在小号） -构型或减少到十分之一1α，25-二羟基维生素d的3与化合物（20 R）-配置。
• 1-Desoxy analog of 2MD: Synthesis and biological activity of (20S)-25-hydroxy-2-methylene-19-norvitamin D3
  作者：Izabela Sibilska、Katarzyna M. Barycka、Rafal R. Sicinski、Lori A. Plum、Hector F. DeLuca

  DOI：10.1016/j.jsbmb.2010.03.063

  日期：2010.7

  During our ongoing structure-activity studies in the vitamin D area, we obtained (20S)-1 alpha,25-dihydroxy-2-methylene-19-norvitamin D-3 (5). This analog, designated 2MD, is characterized by a significantly enhanced calcemic activity and is currently evaluated as a potential drug for osteoporosis. Therefore, it was of interest to synthesize also its 1-desoxy analog and to evaluate its biological action. These studies were aimed at solving an intriguing problem: can such a vitamin also be hydroxylated in vivo at the allylic C-1 position despite lack of the exomethylene moiety at C-10? The Wittig-Horner coupling of the known protected (20S)-25-hydroxy Grundmann ketone 17 and the phosphine oxides 16 and 33, differing in their hydroxyls protection, provided the target 1-desoxy-2MD (6) after removal of the silyl protecting groups. Two synthetic paths have been elaborated leading to the desired A-ring synthons and starting from commercially available compounds:1,4-cyclohexanedione monoethylene acetal (7) and (-)-quinic acid (19). The biological activity in vitro of the synthesized 1-desoxy-2MD (6) was evaluated and this analog was found to have an affinity for the vitamin D receptor (VDR) similar as its parent compound 2MD (5) while being much less active in the transcriptional assay. The results of the biological tests in vivo are also discussed. (C) 2010 Published by Elsevier Ltd.