(3S,5S)-3-tert-butylcarbonyloxy-5-(tert-butyldimethylsilanyloxy)-cyclohexan-1-one | 332097-64-0

• 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: (3S,5S)-3-tert-butylcarbonyloxy-5-(tert-butyldimethylsilanyloxy)-cyclohexan-1-one
• 英文别名: (1S,3S)-2,2-dimethyl-propionic acid 3-(tert-butyl-dimethyl-silanyloxy)-5-oxo-cyclohexyl ester；[(1S,3S)-3-[tert-butyl(dimethyl)silyl]oxy-5-oxocyclohexyl] 2,2-dimethylpropanoate
• CAS: 332097-64-0
• 化学式: C₁₇H₃₂O₄Si
• 分子量: 328.524
• InChiKey: GDYHXPSDTBQJIJ-ZIAGYGMSSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.09
• 重原子数：
  22
• 可旋转键数：
  6
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.88
• 拓扑面积：
  52.6
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  、 (3S,5S)-3-tert-butylcarbonyloxy-5-(tert-butyldimethylsilanyloxy)-cyclohexan-1-one 在 lithium hexamethyldisilazane 作用下， 以 四氢呋喃 为溶剂， 反应 3.5h， 生成 1α-(tert-butyldimethylsilyloxy)-25-(methoxymethoxy)-19-norvitamin D₃ 3-pivaloyl ester 、 1α-(pivaloyloxy)-25-(methoxymethoxy)-19-norvitamin D₃ 3-(tert-butyldimethylsilyl) ether
  参考文献：
  名称：

  Crystal Structures of Hereditary Vitamin D-Resistant Rickets-Associated Vitamin D Receptor Mutants R270L and W282R Bound to 1,25-Dihydroxyvitamin D₃ and Synthetic Ligands

  摘要：

  The vitamin D receptor (VDR), a member of the nuclear receptor superfamily, functions as a ligand-dependent transcription factor for various genes. Hereditary vitamin D-resistant rickets (HVDRR), an autosomal recessive disease, is caused by mutations in the VDR In particular, the missense mutations R274L and W286R in the ligand-binding domain of the VDR can severely reduce or even eliminate natural hormone responsiveness. Here, we report a crystal structure analysis of the R270L and W282R mutants of rat VDR (human R274L and W286R, respectively) in complex with the natural hormone and synthetic ligands. We also studied the folding properties of the mutant proteins by using circular dichroism spectra. Our study indicates that these mutations result in only local structural modifications. We discuss why these mutations disrupt the VDR function and provide clues to develop effective ligands for the treatment of HVDRR

  DOI：

  10.1021/jm400537h
• 作为产物：
  描述：

  all-cis-5-(tert-butyldimethyl-silanyloxy)-cyclohexane-1,3-diol 在 碳酸氢钠 2,2,6,6-tetramethyl-piperidine-N-oxyl 、 sodium hypochlorite 、 Lipase QL 、 偶氮二甲酸二异丙酯 、 potassium carbonate 、 三苯基膦 、 potassium bromide 作用下， 以 四氢呋喃 、 甲醇 、 二氯甲烷 、 水 、 乙酸乙酯 为溶剂， 反应 56.0h， 生成 (3S,5S)-3-tert-butylcarbonyloxy-5-(tert-butyldimethylsilanyloxy)-cyclohexan-1-one
  参考文献：
  名称：

  对映体纯的19- nor，des -C，D维生素D 3衍生物的新颖通用方法

  摘要：

  已经开发了一种短而有效的从头途径到潜在的抗银屑病的des -C，D维生素D 3衍生物3（Ro 65-2299）。这条路线的特点是迄今为止在维生素D化学中尚未探索的组装策略，该策略涉及对A环酮30和2-苯并噻唑基砜60进行改进的Julia烯化反应。A环结构单元的构建是通过高效的三步路线完成的，该路线从内消旋-1,3,5-环己烷三醇（26）开始，该过程通过相应三乙酸酯的高选择性酶促单水解反应来消除对称性。27，然后氧化酒精用图29所示的方法得到的纯手性二乙酰氧基酮30（ee ＝ 99.5％），总产率为83％。此外，我们发现了5-乙酰氧基-2-环己烯酮（31）及其对映异构体32的有效和实用合成方法，这两种新方法都可用于天然产物的合成。

  DOI：

  10.1016/s0040-4020(00)01035-8

文献信息

• Process for preparing retiferol derivatives
  申请人：——

  公开号：US20020028975A1

  公开（公告）日：2002-03-07

  A new process prepares retiferol derivatives of formula I: 1 wherein A is —C≡C— or —CH═CH—, and R 1 and R 2 are independently of each other lower alkyl or lower perfluoroalkyl, one version couples ketones of formula II with compounds of formula III A second version couples phosphinoxides of formula IV with aldehydes of formula V. Compounds of formula I are useful in the treatment or prevention of hyperproliferative skin diseases and for reversing the conditions associated with photodamage.

  一种新的工艺制备了公式I：1的视黄醇衍生物： 其中A为—C≡C—或—CH═CH—，且R1和R2分别为较低的烷基或较低的全氟烷基，其中一个版本将公式II的酮与公式III的化合物偶联，另一个版本将公式IV的膦氧化物与公式V的醛偶联。公式I的化合物在治疗或预防皮肤过度增生性疾病以及逆转与光损伤相关的状况方面有用。
• Enzymatic processes for producing intermediates useful in the manufacture of retiferol derivatives
  申请人：Basilea Pharmaceutica AG

  公开号：US06403346B1

  公开（公告）日：2002-06-11

  Enzymatic processes can produce intermediates for manufacturing retiferol derivatives that are useful for treating or preventing hyperproliferative skin diseases and for reversing conditions associated with photodamage. These processes can use as a starting material trihydroxycyclohexane, which can be chemically modified by a process that includes an enzymatic step, typically involving lipases of EC-class 3.1.1.3 or 3.1.1.34.

  酶促过程可以产生中间体，用于制造对治疗或预防过度增生性皮肤疾病和逆转与光损伤相关的状况有用的维生素A衍生物。这些过程可以使用三羟基环己烷作为起始材料，该材料可以通过包括酶促步骤的化学修饰过程进行改性，通常涉及EC类3.1.1.3或3.1.1.34的脂肪酶。
• Novel versatile approach to an enantiopure 19-nor, des-C,D vitamin D3 derivative
  作者：Hans Hilpert、Beat Wirz

  DOI：10.1016/s0040-4020(00)01035-8

  日期：2001.1

  A short and efficient de novo route to the des-C,D vitamin D3 derivative 3 (Ro 65-2299), a potential antipsoriatic, has been developed. This route features an assembly strategy so far unexplored in vitamin D chemistry involving a modified Julia olefination of the A-ring ketone 30 and the 2-benzothiazolyl sulfone 60. Construction of the A-ring building block was accomplished by an efficient three-step

  已经开发了一种短而有效的从头途径到潜在的抗银屑病的des -C，D维生素D 3衍生物3（Ro 65-2299）。这条路线的特点是迄今为止在维生素D化学中尚未探索的组装策略，该策略涉及对A环酮30和2-苯并噻唑基砜60进行改进的Julia烯化反应。A环结构单元的构建是通过高效的三步路线完成的，该路线从内消旋-1,3,5-环己烷三醇（26）开始，该过程通过相应三乙酸酯的高选择性酶促单水解反应来消除对称性。27，然后氧化酒精用图29所示的方法得到的纯手性二乙酰氧基酮30（ee ＝ 99.5％），总产率为83％。此外，我们发现了5-乙酰氧基-2-环己烯酮（31）及其对映异构体32的有效和实用合成方法，这两种新方法都可用于天然产物的合成。
• Crystal Structures of Hereditary Vitamin D-Resistant Rickets-Associated Vitamin D Receptor Mutants R270L and W282R Bound to 1,25-Dihydroxyvitamin D₃ and Synthetic Ligands
  作者：Makoto Nakabayashi、Yoshito Tsukahara、Yukiko Iwasaki-Miyamoto、Mika Mihori-Shimazaki、Sachiko Yamada、Satomi Inaba、Masayuki Oda、Masato Shimizu、Makoto Makishima、Hiroaki Tokiwa、Teikichi Ikura、Nobutoshi Ito

  DOI：10.1021/jm400537h

  日期：2013.9.12

  The vitamin D receptor (VDR), a member of the nuclear receptor superfamily, functions as a ligand-dependent transcription factor for various genes. Hereditary vitamin D-resistant rickets (HVDRR), an autosomal recessive disease, is caused by mutations in the VDR In particular, the missense mutations R274L and W286R in the ligand-binding domain of the VDR can severely reduce or even eliminate natural hormone responsiveness. Here, we report a crystal structure analysis of the R270L and W282R mutants of rat VDR (human R274L and W286R, respectively) in complex with the natural hormone and synthetic ligands. We also studied the folding properties of the mutant proteins by using circular dichroism spectra. Our study indicates that these mutations result in only local structural modifications. We discuss why these mutations disrupt the VDR function and provide clues to develop effective ligands for the treatment of HVDRR