(1R,3S)-1-(2-dimethylmalonyl)-3-(tert-butyl-dimethylsiloxy)-4-cyclopentene | 426226-00-8

• 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: (1R,3S)-1-(2-dimethylmalonyl)-3-(tert-butyl-dimethylsiloxy)-4-cyclopentene
• 英文别名: dimethyl (1R,4S)-4-[(tert-butyldimethylsilyl)oxy]-2-cyclopenten-1-yl malonate；dimethyl 2-((1R,4S)-4-((tert-butyldimethylsilyl)oxy)cyclopent-2-en-1-yl)malonate；dimethyl(1R,4S)-4-[(tert-butyldimethylsilyl)oxy]-2-cyclopentene-1-yl malonate；dimethyl 2-[(1R,4S)-4-[tert-butyl(dimethyl)silyl]oxycyclopent-2-en-1-yl]propanedioate
• CAS: 426226-00-8
• 化学式: C₁₆H₂₈O₅Si
• 分子量: 328.481
• InChiKey: SULAABWINFBMIR-NWDGAFQWSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.92
• 重原子数：
  22
• 可旋转键数：
  8
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.75
• 拓扑面积：
  61.8
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  (1R,3S)-1-(2-dimethylmalonyl)-3-(tert-butyl-dimethylsiloxy)-4-cyclopentene 在 四丁基氟化铵 、 potassium iodide 作用下， 以 四氢呋喃 、 水 为溶剂， 反应 20.0h， 生成 2-((1s,4s)-4-羟基-2-环戊烯基)乙酸甲酯
  参考文献：
  名称：

  (+)-去甲苷、(+)-Dasycarpidone和(+)-Uleine的对映选择性全合成

  摘要：

  uleine 型生物碱的结构特征在于存在桥连的四环六氢-1 H -1,5-methanoazocino[4,3- b ]indole 环系统1。已经开发了各种策略来访问这种多环结构基序。我们在此报告适当官能化的1,3,4-三取代的环戊-1-烯的一步法转化成1通过一个集成的氧化/还原/环化（的方式我ORC）过程。该多米诺序列由环戊烯环的氧化裂解引发，随后通过形成一个 C-C 和两个 CN 键生成环己烯酮、吲哚和 1,3-桥接哌啶环。化合物1随后转化为nordasycarpidone、dasycarpidone和uleine。分子的手性通过市售的内消旋-3,5-二乙酰氧基-1-环戊烯的酶促去对称化引入。

  DOI：

  10.1002/hlca.202100088
• 作为产物：
  描述：

  Cis-3,5-二乙酰氧基-1-环戊烯 在 4-二甲氨基吡啶 、 potassium tert-butylate 、 Candida Antartica CAL-B 、 三乙胺 作用下， 以 四氢呋喃 、 aq. phosphate buffer 、 二氯甲烷 为溶剂， 反应 36.17h， 生成 (1R,3S)-1-(2-dimethylmalonyl)-3-(tert-butyl-dimethylsiloxy)-4-cyclopentene
  参考文献：
  名称：

  TiCl3介导的2,3,3-三取代的吲哚啉的合成：（+）-1,2-脱氢aspidospermidine，（+）-Condyfoline和（-）-Tubifoline的总合成。

  摘要：

  2,3,3-三取代的吲哚啉构成许多生物学上重要的单萜吲哚生物碱的组成部分。我们在这里报告说TiCl 3前所未有地进入了这个骨架介导的带有2-硝基苯基取代基的四取代烯烃的还原环化。首先通过完成简明的（+）-1,2-脱氢天冬酰胺亚精胺的全合成来证明概念验证，其特征是该关键转化的后期应用。建议将硝基芳烃还原为亚硝基芳烃，然后进行6π-电子-5原子电环化，然后将所得的硝酮中间体进行1,2-烷基转移，以说明反应的结果。随后的（+）-con啶啉的全合成不仅说明了反应的一般性，而且还提供了对1,2-烷基转移的性质的机械了解。（+）-con啶啉的独家形成表明1,2-烷基迁移遵循Wagner-Meerwein协同路径，而不是逐步的逆曼尼希/曼尼希反应序列。还记录了通过逆曼尼希/ 1,3-原生质体/环环形环化级联将（+）-dy啶茶碱几乎定量转化为（-）-tub茶碱的条件。

  DOI：

  10.1002/anie.202005380

文献信息

• Total synthesis of Δ12-PGJ2, 15-deoxy-Δ12,14-PGJ2, and related compounds
  作者：Hukum P. Acharya、Yuichi Kobayashi

  DOI：10.1016/j.tetlet.2003.11.143

  日期：2004.2

  α′-position with the ω-chain aldehydes followed by dehydration to produce the title compounds. In a similar manner, 5-dehydro compounds (acetylene analogues) were synthesized successfully. In addition, palladium-catalyzed reaction of 4-cyclopentene-1,3-diol monoacetate with methyl malonate, the first step of the synthesis, was improved to afford the product in high yield by using t-BuOK or LDA in place

  具有α链的关键环戊烯酮，从4-环戊烯-1,3-二醇单乙酸酯的TBS醚合成，并且在提交给醛醇缩合反应的α '位上与ω-链醛，然后脱水，产生标题化合物。以类似的方式，成功地合成了5-脱氢化合物（乙炔类似物）。另外，通过使用t- BuOK或LDA代替NaH ，改进了合成的第一步钯-催化的4-环戊烯-1，3-二醇单乙酸酯与丙二酸甲酯的反应，从而以高收率提供了产物。
• Highly efficient total synthesis of Δ12-PGJ2, 15-deoxy-Δ12,14-PGJ2, and their analogues
  作者：Hukum P. Acharya、Yuichi Kobayashi

  DOI：10.1016/j.tet.2006.01.051

  日期：2006.4

  Palladium-catalyzed reaction of TBS ether of 4-cyclopentene-1,3-diol monoacetate (>95% ee) with an anion derived from methyl malonate and a base such as t-BuOK and LDA proceeded highly efficiently and reproducibly. The product obtained in >90% isolated yield was transformed in five steps into the key cyclopentenone possessing the α-chain at the γ position. Aldol reaction of this enone with the ω-chain aldehyde afforded

  4-环戊烯-1,3-二醇单乙酸酯（> 95％ee）的TBS醚与衍生自丙二酸甲酯的阴离子和t- BuOK和LDA等碱的钯催化反应进行得非常高效且可重复。以> 90％的分离产率获得的产物经五步转化为在γ位具有α链的关键环戊烯酮。该烯酮与ω-链醛的醛醇缩合反应得到醛醇加合物，并且将衍生的甲磺酸酯暴露于Al 2 O 3提供了完整结构的交联二烯酮。最后，官能团操作布置Δ 12 -PGJ 2有效。同样，15-脱氧Δ 12,14 -PGJ 2合成了5，6-乙炔类似物和5，6-二氢类似物。
• TiCl₃‐Mediated Synthesis of 2,3,3‐Trisubstituted Indolenines: Total Synthesis of (+)‐1,2‐Dehydroaspidospermidine, (+)‐Condyfoline, and (−)‐Tubifoline
  作者：Bastien Delayre、Cyril Piemontesi、Qian Wang、Jieping Zhu

  DOI：10.1002/anie.202005380

  日期：2020.8.10

  for the reaction outcome. A subsequent total synthesis of (+)‐condyfoline not only illustrates the generality of the reaction, but also provides a mechanistic insight into the nature of the 1,2‐alkyl shift. The exclusive formation of (+)‐condyfoline indicates that the 1,2‐alkyl migration follows a concerted Wagner–Meerwein pathway, rather than a stepwise retro‐Mannich/Mannich reaction sequence. Conditions

  2,3,3-三取代的吲哚啉构成许多生物学上重要的单萜吲哚生物碱的组成部分。我们在这里报告说TiCl 3前所未有地进入了这个骨架介导的带有2-硝基苯基取代基的四取代烯烃的还原环化。首先通过完成简明的（+）-1,2-脱氢天冬酰胺亚精胺的全合成来证明概念验证，其特征是该关键转化的后期应用。建议将硝基芳烃还原为亚硝基芳烃，然后进行6π-电子-5原子电环化，然后将所得的硝酮中间体进行1,2-烷基转移，以说明反应的结果。随后的（+）-con啶啉的全合成不仅说明了反应的一般性，而且还提供了对1,2-烷基转移的性质的机械了解。（+）-con啶啉的独家形成表明1,2-烷基迁移遵循Wagner-Meerwein协同路径，而不是逐步的逆曼尼希/曼尼希反应序列。还记录了通过逆曼尼希/ 1,3-原生质体/环环形环化级联将（+）-dy啶茶碱几乎定量转化为（-）-tub茶碱的条件。
• Synthesis of Coronafacic Acid via TBAF-Assisted Elimination of the Mesylate and Its Conversion to the Isoleucine Conjugate
  作者：Yusuke Kosaki、Narihito Ogawa、Qian Wang、Yuichi Kobayashi

  DOI：10.1021/ol201576c

  日期：2011.8.19

  derived mesylate was used to construct the side chain that was designed to afford the cyclohexene ring of coronafacic acid via intramolecular alkylation. Elimination of the mesylate proceeded with TBAF. The alkylation was achieved with t-BuOK in THF, and then hydrolysis afforded coronafacic acid, which upon condensation with unprotected l-isoleucine using ClCO2Bui furnished coronafacoyl-l-isoleucine, the

  使用醛醇缩合反应，随后消除衍生的甲磺酸酯，以构建侧链，该侧链经设计以通过分子内烷基化提供冠糖酸的环己烯环。TBAF消除了甲磺酸盐。该烷基化用实现吨在THF -BuOK，然后水解，得到酸晕斑，其在与未受保护的缩合升使用ClCO -异亮氨酸2卜我布置coronafacoyl-升-异亮氨酸，所述升-Ile缀合物。
• Metal Coordination-Based Inhibitors of Adenylyl Cyclase:  Novel Potent P-Site Antagonists
  作者：Daniel E. Levy、Ming Bao、Diana B. Cherbavaz、James E. Tomlinson、David M. Sedlock、Charles J. Homcy、Robert M. Scarborough

  DOI：10.1021/jm0205604

  日期：2003.5.1

  The adenylyl cyclases (ACS) are a family of intracellular enzymes associated with signal transduction by virtue of their ability to convert ATP to cAMP. The catalytic mechanism of this transformation proceeds through initial binding of ATP to the so-called purine binding site (P-site) of the enzyme followed by metal-mediated cyclization with loss of pyrophosphate. Crystallographic analysis of ACs with known inhibitors reveals the presence of two metals in the active site. Presently, nine isoforms of adenylyl cyclase are known, and unique isoform combinations are expressed in a tissue-specific manner. The development of isoform-specific inhibitors of adenylyl cyclase may prove to be a useful strategy toward the design of unique signal transduction inhibitors. To develop novel AC inhibitors, we have chosen an approach to inhibitor design utilizing an adenine ring system joined to a metal-coordinating hydroxamic acid via various linkers. Previous work in our group has validated this approach and identified novel inhibitors that possess an adenine ring joined to a metal-coordinating hydroxamic acid through flexible acyclic linkers (Levy, D. E., et al. Bioorg. Med. Chem. Lett. 2002, 12, 30853088). Subsequent studies have focused on the introduction of conformational restrictions into the tether of the inhibitors with the goal of increasing potency (Levy, D. E., et al. Bioorg. Med. Chem. Lett. 2002, 12, 3089-3092). Building upon the favorable spatial positioning of the adenine and hydroxamate groups coupled with potentially favorable entropic factors, the unit joining the carbocycle to the hydroxamate was explored further and a stereochemical-based SAR was elucidated, leading to a new series of highly potent AC inhibitors.