(3R,5R)-3,5-bis-[(tert-butyldimethylsilyl)oxy]-4-[(trimethylsilyl)oxy]cyclohexanone | 141404-09-3

• 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-butyldimethylsilyl)oxy]-4-[(trimethylsilyl)oxy]cyclohexanone
• 英文别名: (3R,5R)-3,5-bis<(tert-butyldimethylsilyl)oxy>-4-<(trimethylsilyl)oxy>cyclohexanone；(3R,5R) [3,5-Bis (tert.-butyldimethylsilyloxy)-4-tri-methylsilyloxy]-1-cyclohexanone；(3R,5R)-3,5-bis-[(t-butyldimethylsilyl)oxy]-4-[(trimethylsilyl)oxy]-cyclohexanone；(3R,5R)-3,5-bis[[tert-butyl(dimethyl)silyl]oxy]-4-trimethylsilyloxycyclohexan-1-one
• CAS: 141404-09-3
• 化学式: C₂₁H₄₆O₄Si₃
• 分子量: 446.85
• InChiKey: GAXPOBFIIBZPRB-QZTJIDSGSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.35
• 重原子数：
  28
• 可旋转键数：
  8
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.95
• 拓扑面积：
  44.8
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  (3R,5R)-3,5-bis-[(tert-butyldimethylsilyl)oxy]-4-[(trimethylsilyl)oxy]cyclohexanone 在 palladium on activated charcoal 咪唑 、 sodium tetrahydroborate 、 正丁基锂 、 草酰氯 、 氢气 、 sodium hydride 、 二异丁基氢化铝 、 溶剂黄146 、 二甲基亚砜 、 三乙胺 、 lithium diisopropyl amide 作用下， 以 四氢呋喃 、 乙醇 、 正己烷 、 二氯甲烷 、 水 、 N,N-二甲基甲酰胺 、 甲苯 为溶剂， 反应 39.5h， 生成 (3R,5R)-[3,5-bis-[(tert-butyldimethylsilyl)oxy]-4-[2-(tert-butyldimethylsilyl)oxyethyl]cyclohexylidene]ethanol
  参考文献：
  名称：

  Synthesis and biological activities of new 1α,25-dihydroxy-19-norvitamin D3 analogs with modifications in both the A-ring and the side chain

  摘要：

  In a series of studies on structure-activity relationships of 2-substituted 19-norvitamin D analogs, we found that 1 alpha,25-dihydroxy-19-norvitamin D-3 analogs with 2 beta-hydroxyethoxy or 2E-hydroxyethylidene moieties show strong binding affinity for the vitamin D receptor (VDR) as well as marked transcriptional activity. To further examine the effects of side chain structure on the activity of 2-substituted 19-norvitamin D analogs, we have synthesized new 19-norvitamin D3 analogs with modifications in both the A-ring at the C(2) position and the side chain. The side chains of these analogs contained a double bond between C(22) and C(23) or an oxygen atom at C(22). The biological activity of the analogs was evaluated in vitro. All the side chain-modified analogs were less active than 1 alpha,25-dihydroxyvitamin D-3 1e and the parent compounds 3-6e possessing a natural 20R-configuration in binding to the VDR, but, except for the (20R)-22-oxa analogs 3-6d, were significantly more potent in transcriptional activity. Of the side-chain-modified analogs 4 and 5, the 2 beta-hydroxyethoxy- and 2E-hydroxyethylidene-22,24-diene-24a,26a,27a-trihorno analogs showed markedly higher transcriptional activity (25- and 17.5-fold, respectively) compared with le. Elongation of the side chain at the C-24, C-26, and C-27 positions and introduction of a 22,24-diene moiety strongly increased transcriptional activity, as seen in the 20-epi analogs 3-6f. (c) 2006 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2006.01.061
• 作为产物：
  描述：

  methyl 4,6-O-benzylidene-2-deoxy-α-D-glucopyranoside 在 palladium on activated charcoal 吡啶 、 lithium aluminium tetrahydride 、 三氯化铝 、 草酰氯 、 四丁基氟化铵 、 水 、 氢气 、 碘 、 silver fluoride 、 L-Selectride 、 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-butyldimethylsilyl)oxy]-4-[(trimethylsilyl)oxy]cyclohexanone
  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。
• New derivatives of 1α,25-dihydroxy-19-norvitamin D3 with two substituents at C-2: synthesis and biological activity
  作者：Masato Shimizu、Yukiko Iwasaki、Mika Shimazaki、Youhei Amano、Keiko Yamamoto、Wolfgang Reischl、Sachiko Yamada

  DOI：10.1016/j.bmcl.2004.12.090

  日期：2005.3

  To examine the effect of 2,2-disubstitution on the biological activities of 19-norvitamin D analogs, novel 2,2-disubstituted-(20R)- and (20S)-1alpha,25-dihydroxy-19-norvitamin D3 analogs were prepared and their biological activities were studied. All the synthesized analogs possessing hydrophobic 2alpha-substituents were more active than the corresponding 2beta-isomers both in binding to the vitamin

  为了检查2,2-二取代对19-norvitamin D类似物的生物学活性的影响，制备了新型2,2-二取代-（（20R）-和（20S）-1alpha，25-dihydroxy-19-norvitamin D3类似物并对其生物学活性进行了研究。所有具有疏水性2α-取代基的合成类似物在与维生素D受体结合和激活基因转录方面都比相应的2β-异构体更具活性。发现2α-甲基-2β-羟基类似物9b具有比天然配体1a显着更高的转录活性（32倍），尽管两者对维生素D受体具有相同的结合亲和力。据我们所知，该类似物是最有效的19-维生素D类似物之一。
• 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。
• EP1559708
  申请人：——

  公开号：——

  公开（公告）日：——
• 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.