(3R,5R)-3,5-bis[tert-butyl(dimethyl)silyloxy]-4-hydroxycyclohexanone | 141404-08-2

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: (3R,5R)-3,5-bis[tert-butyl(dimethyl)silyloxy]-4-hydroxycyclohexanone
• 英文别名: (3R,5R) [3,5-Bis(tert.-butyldimethylsilyloxy), 4-hydroxy]-1-cyclohexanone；(3R,5R)-3,5-bis[[tert-butyl(dimethyl)silyl]oxy]-4-hydroxycyclohexan-1-one
• CAS: 141404-08-2
• 化学式: C₁₈H₃₈O₄Si₂
• 分子量: 374.668
• InChiKey: WXSHSLZNMIOUPW-HUUCEWRRSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.49
• 重原子数：
  24
• 可旋转键数：
  6
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.94
• 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：

  (3R,5R)-3,5-bis[tert-butyl(dimethyl)silyloxy]-4-hydroxycyclohexanone 在 ruthenium trichloride sodium periodate 、 正丁基锂 、 双氧水 、 lithium diisopropyl amide 作用下， 以 四氢呋喃 、 四氯化碳 、 正己烷 、 二氯甲烷 、 水 、 乙腈 为溶剂， 反应 33.03h， 生成 [2-[(3'R,5'R)-3',5'-bis[(tert-butyldimethylsilyl)oxy]-4'-ethylidenecyclohexylidene]ethyl]diphenylphosphine oxide
  参考文献：
  名称：

  1alpha，25-dihydroxy-19-norvitamin D（3）的2-乙基和2-亚乙基类似物：合成，构象分析，生物活性，和对接的模型rVDR配体结合域。

  摘要：

  制备新型的19-nor类似物1alpha，25-dihydroxyvitamin D（3），并在C-2处被亚乙基取代。合成途径是通过相应的A环膦氧化物与受保护的25-羟基Grundmann酮的Wittig-Horner偶联进行的。2-亚乙基类似物的选择性催化氢化提供了2α-和2β-乙基化合物。与亚乙基部分具有甲基的2-亚乙基-19-nor化合物与C（6）-C（7）键（E-异构体）成反式关系，比相应的Z-异构体和天然化合物更有效激素与维生素D受体结合。（20S）-2-亚乙基-19-norvitamin D（3）的两个几何异构体（E和Z）和2α-乙基-19-norvitamins的两个几何异构体（在20R和20S系列中）均具有更高的HL-60区分度活性比1alpha，25-（OH）（2）D（3）大。2-亚乙基维生素的两种E-异构体（20R和20S）的特征是大鼠的钙化活性非常高。还报告了大鼠维生

  DOI：

  10.1021/jm020007m
• 作为产物：
  描述：

  methyl 3,4,6-tri-O-acetyl-2-deoxy-α-D-arabino-hexopyranoside 在 palladium on activated charcoal 吡啶 、 甲醇 、 lithium aluminium tetrahydride 、 三氯化铝 、 草酰氯 、 四丁基氟化铵 、 水 、 氢气 、 碘 、 sodium methylate 、 silver fluoride 、 L-Selectride 、 对甲苯磺酸 、 二甲基亚砜 、 三苯基膦 、 palladium dichloride 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 乙醚 、 乙醇 、 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 生成 (3R,5R)-3,5-bis[tert-butyl(dimethyl)silyloxy]-4-hydroxycyclohexanone
  参考文献：
  名称：

  Novel synthesis of 2-Substituted 19-norvitamin D A-ring phosphine oxide from d-glucose as a building block

  摘要：

  19-Norvitamin D A-ring phosphine oxide 5 was synthesized by a new sequence mode starting from D-glucose as a chiral template. Transformation of the pyranoside ring into the A-ring carbocycle was achieved by the Pd-catalyzed Ferrier rearrangement. The phosphine oxide 5 was obtained in an 18% overall yield by this novel cost-effective method. (C) 2003 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0960-894x(03)00005-2

文献信息

• Synthesis of a-ring synthon of 19-nor-1alpha,25-dihydroxyvitamin D3 from (D)-glucose
  申请人：——

  公开号：US20040133026A1

  公开（公告）日：2004-07-08

  The present invention provides a method for the synthesis of an A-ring synthon phosphine oxide used in the preparation of 19-nor vitamin D compounds, and to novel synthetic intermediates formed during the synthesis. The new method prepares the phosphine oxide from (D)-glucose.

  本发明提供了一种合成A环合成子膦氧化物的方法，该方法用于制备19-去甲维生素D化合物，并且提供了在合成过程中形成的新型合成中间体。这种新方法是从（D）-葡萄糖制备膦氧化物。
• 19-Nor-vitamin D.sub.3 compounds with substitutent at 2-position
  申请人：Wisconsin Alumni Research Foundation

  公开号：US05536713A1

  公开（公告）日：1996-07-16

  The 2.alpha. and 2.beta.-hydroxy as well as the 2.alpha.(3'-hydroxypropoxy)- and 2.beta.(3'-hydroxypropoxy)- and 2.alpha.(benzyloxy)- analogs of 19-nor-1.alpha.,25-dihydroxyvitamin D.sub.3 are disclosed. The two 2-hydroxy analogs showed in vivo calcium transport with little or no bone calcium mobilization; the 2.beta.- more than the 2.alpha.- analog. Both analogs induced differentiation of malignant cells. The two analogs thus show promise in the treatment of osteoporosis. The 2.alpha.-hydroxypropoxy analog showed a selective activity profile, combining high potency in inducing differentiation of malignant cells with very low or no bone calcification activity, a possible use in the treatment of malignancies.

  本文介绍了19-去甲基-1α，25-二羟基维生素D3的2.alpha.和2.beta.羟基以及2.alpha.（3'-羟基丙氧基）-和2.beta.（3'-羟基丙氧基）-和2.alpha.（苄氧基）类似物。两种2-羟基类似物在体内显示出钙转运的作用，几乎不会引起骨钙动员；2.beta.类似物比2.alpha.类似物更有效。两种类似物都能诱导恶性细胞分化。因此，这两种类似物在骨质疏松症的治疗方面显示出潜力。2.alpha.-羟基丙氧基类似物显示出选择性活性，结合了在诱导恶性细胞分化方面的高效率和非常低或没有骨化作用的特点，可能在恶性肿瘤的治疗中有用。
• 2-Methylene 19-nor-25-dehydro-1α-hydroxyvitamin D3 26,23-lactones: Synthesis, biological activities and molecular basis of passive antagonism
  作者：Nobuko Yoshimoto、Yuka Inaba、Sachiko Yamada、Makoto Makishima、Masato Shimizu、Keiko Yamamoto

  DOI：10.1016/j.bmc.2007.09.017

  日期：2008.1

  To investigate the molecular mechanism of vitamin D receptor (VDR) antagonists having no structurally bulky group interfering with helix 12 of the ligand-binding domain of the VDR, we have synthesized four diastereomers at C(20) and C(23) of 19-nor-1 alpha-hydroxyvitamin D-3 25-methylene-26,23-lactone bearing a 2MD-type A-ring. All four analogs showed significant VDR affinity. Transactivation was tested by using Cos7 cells and HEK293 cells. In both types of cells, LAC67a showed little transactivation potency and inhibited the activation induced by the natural hormone concentration-dependently, indicating that LAC67a works as an antagonist for the VDR in these cells. LAC67b, LAC82a and LAC82b similarly acted as VDR antagonists in Cos7 cells, but in HEK293 cells they behaved as potent VDR agonists. Docking of four lactones into the VDR-LBD, followed by structural analysis, demonstrated that each lactone lacks the hydrophobic interaction with helix12 necessary for maintaining the active conformation of the VDR, indicating that these lactones are passive-type antagonists. Furthermore, each docking structure explained the characteristic transactivation profiles of the four lactones. On the basis of our present findings, we suggest that the ligand acts as an agonist if there are appropriate coactivators in the cells to bind to the looser VDR-ligand complex, and as an antagonist if there are no such appropriate coactivators. The molecular basis of the passive antagonism is discussed in detail. (c) 2007 Elsevier Ltd. All rights reserved.
• Synthesis and Biological Activity of 2-Hydroxy and 2-Alkoxy Analogs of 1.alpha.,25-Dihydroxy-19-norvitamin D3
  作者：Rafal R. Sicinski、Kato L. Perlman、Hector F. DeLuca

  DOI：10.1021/jm00048a009

  日期：1994.10

  1 alpha,2 alpha,25 Trihydroxy-19-norvitamin D-3, 1 alpha,2 beta,25-trihydroxy-19-norvitamin D-3, and their alkoxy analogs were efficiently prepared in a convergent synthesis, starting with (-)-quinic acid and a Windaus-Grundmann type ketone. Configurations of the A-ring fragment substituents were determined by H-1,H-1 COSY 2D spectra and H-1 NOE difference spectroscopy. The new analogs exhibited selective activity in stimulating intestinal calcium transport while having little or no activity in mobilizing bone calcium. They also showed HL-60-differentiating activity equal to or 10 times lower than that of 1 alpha,25-dihydroxyvitamin D-3.