2,2-二甲基-gamma-己内酯; 5-乙基二氢-3,3-二甲基-2(3H)-呋喃酮 | 54491-23-5

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 内酯类
• 中文名称: 2,2-二甲基-gamma-己内酯; 5-乙基二氢-3,3-二甲基-2(3H)-呋喃酮
• 中文别名: 2,2-二甲基-gamma-己内酯;5-乙基二氢-3,3-二甲基-2(3H)-呋喃酮
• 英文名称: 2,2-dimethyl-4-hydroxyhexanoic acid γ-lactone
• 英文别名: dihydro-3,3-dimethyl-5-ethyl-2(3H)-furanone；dihydro-5-ethyl-3,3-dimethyl-2(3H)-furanone；5-ethyl-3,3-dimethyldihydrofuran-2(3H)-one；5-ethyl-3,3-dimethyldihydrofuran-2-one；5-ethyl-3,3-dimethyl-dihydro-furan-2-one；5-Ethyl-3,3-dimethyloxolan-2-one
• CAS: 54491-23-5
• 化学式: C₈H₁₄O₂
• 分子量: 142.198
• InChiKey: DFJKSWYZVSYBRF-UHFFFAOYSA-N

物化性质

• 沸点：
  214℃
• 密度：
  0.934
• 闪点：
  79℃

计算性质

• 辛醇/水分配系数(LogP)：
  2.1
• 重原子数：
  10
• 可旋转键数：
  1
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.88
• 拓扑面积：
  26.3
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  2,2-二甲基-gamma-己内酯; 5-乙基二氢-3,3-二甲基-2(3H)-呋喃酮 在 sodium hydroxide 、 sodium chloride dihydrate 、 ruthenium(IV) oxide hydrate 作用下， 以 水 为溶剂， 反应 1.0h， 以0.57 g的产率得到2,2-二甲基-4-氧代己酸
  参考文献：
  名称：

  Development of Potent and Selective Indomethacin Analogues for the Inhibition of AKR1C3 (Type 5 17β-Hydroxysteroid Dehydrogenase/Prostaglandin F Synthase) in Castrate-Resistant Prostate Cancer

  摘要：

  Castrate-resistant prostate cancer (CRPC) is a fatal, metastatic form of prostate cancer. CRPC is characterized by reactivation of the androgen axis due to changes in androgen receptor signaling and/or adaptive intratumoral androgen biosynthesis. AKR1C3 is upregulated in CRPC where it catalyzes the formation of potent androgens. This makes AKR1C3 a target for the treatment of CRPC. AKR1C3 inhibitors should not inhibit AKR1C1/AKR1C2, which inactivate 5 alpha-dihydrotestosterone. Indomethacin, used to inhibit cyclooxygenase, also inhibits AKR1C3 and displays selectivity over AKR1C1/AKR1C2. Parallel synthetic strategies were used to generate libraries of indomethacin analogues, which exhibit reduced cyclooxygenase inhibitory activity but retain AKR1C3 inhibitory potency and selectivity. The lead compounds inhibited AKR1C3 with nanomolar potency, displayed >100-fold selectivity over AKR1C1/AKR1C2, and blocked testosterone formation in LNCaP-AKR1C3 cells. The AKR1C3.NADP(+).2'-des-methyl-indomethacin crystal structure was determined, and it revealed a unique inhibitor binding mode. The compounds reported are promising agents for the development of therapeutics for CRPC.

  DOI：

  10.1021/jm3017656
• 作为产物：
  描述：

  methyl 2,2-dimethyl-5-hexenoate 在 sodium hydroxide 、 silver trifluoromethanesulfonate 作用下， 以 甲醇 、 水 、 1,2-二氯乙烷 为溶剂， 反应 15.0h， 生成 2,2-二甲基-gamma-己内酯; 5-乙基二氢-3,3-二甲基-2(3H)-呋喃酮
  参考文献：
  名称：

  在三氟甲磺酸银（I）催化下，将醇和羧酸分子内加成到惰性烯烃中。

  摘要：

  [反应：见正文]描述了在简单的三氟甲磺酸银（I）催化下将羟基或羧基分子内加成至惰性烯烃。在相对温和的条件下，对于一定范围的基材，可以获得良好或优异的产量。该反应代表构建环醚或内酯的最简单方法之一。

  DOI：

  10.1021/ol051065f

文献信息

• Homoaldol and Aldol Reactions from Common Enolates and Oxiranes: Reaction of Reductively Generated Chromium Enolates through Cationic Rearrangement
  作者：Makoto Hojo、Kyosuke Sakata、Xiamuxikamaer Maimaiti、Junya Ueno、Hisashi Nishikori、Akira Hosomi

  DOI：10.1246/cl.2002.142

  日期：2002.2

  Enolates generated from α-bromo esters by the reduction with “Bu6CrLi3” react with oxiranes to afford γ-hydroxy esters and β-hydroxy esters, depending on the Lewis acid used as a promoter.

  α-溴酯通过用“Bu6CrLi3”还原生成的烯醇化物与环氧乙烷反应生成 γ-羟基酯和 β-羟基酯，这取决于用作促进剂的路易斯酸。
• Catalyst-controlled aliphatic C—H oxidations
  申请人：The Board of Trustees of the University of Illinois

  公开号：US09925528B2

  公开（公告）日：2018-03-27

  The invention provides simple small molecule, non-heme iron catalyst systems with broad substrate scope that can predictably enhance or overturn a substrate's inherent reactivity preference for sp3-hybridized C—H bond oxidation. The invention also provides methods for selective aliphatic C—H bond oxidation. Furthermore, a structure-based catalyst reactivity model is disclosed that quantitatively correlates the innate physical properties of the substrate to the site-selectivities observed as a function of the catalyst. The catalyst systems can be used in combination with oxidants such as hydrogen peroxide to effect highly selective oxidations of unactivated sp3 C—H bonds over a broad range of substrates.

  该发明提供了一种简单的小分子、非血红素铁催化体系，具有广泛的底物范围，可以可预测地增强或颠覆底物对sp3杂化C-H键氧化的固有反应性偏好。该发明还提供了选择性脂肪族C-H键氧化的方法。此外，还披露了一种基于结构的催化剂反应性模型，该模型定量地相关底物的固有物理性质与作为催化剂功能的位选择性。这些催化体系可以与过氧化氢等氧化剂结合使用，对广泛的底物范围上的未活化的sp3 C-H键进行高度选择性的氧化。
• A Convenient Lactonization of 2- and 3-Cyclopropylalkanoic Acids to γ- and δ-Lactones
  作者：Kotoji Sugahara、Tsutomu Fujita、Shoji Watanabe、Masami Sakamoto、Ken-ich Sugimoto

  DOI：10.1055/s-1990-27014

  日期：——

  A convenient preparative method of obtaining 2,2,4,5,5-pentaalkyl-δ- valerolactones 2a-d or 2,2,4,4-tetraalkyl-γ-butyrolactones 4a-e by the acid-catalyzed lactonization of 3-cyclopropylalkanoic acids, and for obtaining bicyclo-γ-lactones 6a-d from bicyclic 2-cyclopropylalkanoic acids 5a-d is presented.

  本文介绍了一种制备方法，通过3-环丙基链烷酸的酸催化内酯化反应，可方便地获得2,2,4,5,5-五烷基-γ-戊内酯2a-d或2,2,4,4-四烷基-γ-丁内酯4a-e，以及从双环2-环丙基链烷酸5a-d中获取双环-γ-内酯6a-d。
• CATALYST-CONTROLLED ALIPHATIC C-H OXIDATIONS
  申请人：THE BOARD OF TRUSTEES OF THE UNIVERSITY OF ILLINOIS

  公开号：US20160214097A1

  公开（公告）日：2016-07-28

  The invention provides simple small molecule, non-heme iron catalyst systems with broad substrate scope that can predictably enhance or overturn a Substrate Control Catalyst Control substrate's inherent reactivity preference for sp3-hybridized C—H bond oxidation. The invention also provides methods for selective aliphatic C—H bond oxidation. Furthermore, a structure-based catalyst reactivity model is disclosed that quantitatively correlates the innate physical properties of the substrate to the site-selectivities observed as a function of the catalyst. The catalyst systems can be used in combination with oxidants such as hydrogen peroxide to effect highly selective oxidations of unactivated sp3 C—H bonds over a broad range of substrates.

  本发明提供了简单的小分子、非血红素铁催化剂系统，具有广泛的底物范围，可以可预测地增强或颠覆基质控制催化剂控制底物对sp3杂化C-H键氧化的固有反应性偏好。本发明还提供了选择性脂肪族C-H键氧化的方法。此外，还公开了一种基于结构的催化剂反应性模型，该模型定量地将底物的固有物理性质与作为催化剂函数的位点选择性相互关联。这些催化剂系统可以与过氧化氢等氧化剂结合使用，对广泛的底物进行高度选择性的未活化的sp3 C-H键氧化。
• 10.1021/jacs.4c04043
  作者：Zhuang, Zhe、Sheng, Tao、Qiao, Jennifer X.、Yeung, Kap-Sun、Yu, Jin-Quan

  DOI：10.1021/jacs.4c04043

  日期：——

  carboxylic acids and cycloalkane acetic acids was observed, giving either fused or bridged γ-lactones that are difficult to access by other methods. δ-C–H lactonization was only favored in the presence of tertiary δ-C–H bonds. The synthetic utility of this methodology was demonstrated by the late-stage functionalization of amino acids, drug molecules, and natural products, as well as a two-step total synthesis

  位点选择性C(sp 3 )–H氧化在有机合成和药物发现中具有重要意义。游离羧酸的γ-C(sp 3 )–H内酯化提供了从丰富且廉价的羧酸制备具有生物学重要意义的内酯支架的最直接的方法；然而，具有广泛底物范围的这种转化的多功能催化剂仍然难以捉摸。在此，我们报道了一种简单但广泛适用且可扩展的游离脂肪酸γ-内酯化反应，该反应由铜催化剂与廉价的Selectflu作为氧化剂相结合实现。该内酯化反应表现出与叔键、苄基键、烯丙基键、亚甲基键和伯键 γ-C-H 键的相容性，可生成多种结构多样的内酯，例如螺内酯、稠合内酯和桥连内酯。值得注意的是，观察到环烷羧酸和环烷乙酸的独特γ-亚甲基C-H内酯化，得到稠合或桥联的γ-内酯，这是其他方法难以获得的。仅当存在叔δ-C-H键时，才利于δ-C-H内酯化。该方法的合成效用通过氨基酸、药物分子和天然产物的后期功能化以及(异)薄荷内酯的两步全合成（迄今为止报道的最短合成）得到证明。