[(R)-3'-[(tert-butyldimethylsilyl)oxy]-4'-methylene-cyclohexylidene] acetic acid methyl ester | 1279708-92-7

• 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: [(R)-3'-[(tert-butyldimethylsilyl)oxy]-4'-methylene-cyclohexylidene] acetic acid methyl ester
• 英文别名: methyl 2-[(3R)-3-[tert-butyl(dimethyl)silyl]oxy-4-methylidenecyclohexylidene]acetate
• CAS: 1279708-92-7
• 化学式: C₁₆H₂₈O₃Si
• 分子量: 296.482
• InChiKey: IMSXIMKTDVJFEW-CQSZACIVSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.22
• 重原子数：
  20
• 可旋转键数：
  5
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.69
• 拓扑面积：
  35.5
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  [(R)-3'-[(tert-butyldimethylsilyl)oxy]-4'-methylene-cyclohexylidene] acetic acid methyl ester 在 正丁基锂 、 双氧水 、 二异丁基氢化铝 、 苯基锂 作用下， 以 四氢呋喃 、 二氯甲烷 、 水 为溶剂， 生成 tert-butyldimethyl(((R,E)-5-(2-((1R,3aS,7aR,E)-7a-methyl-1-((S)-6-methyl-6-((triethylsilyl)oxy)heptan-2-yl)octahydro-4H-inden-4-ylidene)ethylidene)-2-methylenecyclohexyl)oxy)silane
  参考文献：
  名称：

  1-Desoxy analog of 2MD: Synthesis and biological activity of (20S)-25-hydroxy-2-methylene-19-norvitamin D3

  摘要：

  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.

  DOI：

  10.1016/j.jsbmb.2010.03.063
• 作为产物：
  描述：

  (1S,5R)-1-hydroxy-6-oxa-bicyclo[3.2.1]octane-4,7-dione 在 sodium periodate 、 potassium tert-butylate 、 二异丁基氢化铝 作用下， 以 四氢呋喃 、 甲醇 、 二氯甲烷 、 水 、 苯 为溶剂， 反应 69.0h， 生成 [(R)-3'-[(tert-butyldimethylsilyl)oxy]-4'-methylene-cyclohexylidene] acetic 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

• 1-Desoxy-2-Methylene-19-Nor-Vitamin D Analogs and Their Uses
  申请人：DeLuca Hector F.

  公开号：US20110082121A1

  公开（公告）日：2011-04-07

  This invention discloses 1-desoxy-2-methylene-19-nor-vitamin D analogs, and specifically (20S)-25-hydroxy-1-desoxy-2-methylene-19-nor-vitamin D 3 and pharmaceutical uses therefor. This compound exhibits 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 leukemia, colon cancer, breast cancer, skin cancer or prostate cancer.

  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。
• 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.