(+)-spirocurcasone | 1426058-46-9

• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 异戊烯醇脂质
• 英文名称: (+)-spirocurcasone
• 英文别名: (+)-Spirocurcasone；(1R,4aR,5S,8aS)-2',3-dimethyl-8-methylidene-5-prop-1-en-2-ylspiro[5,6,7,8a-tetrahydro-4aH-naphthalene-1,5'-cyclopent-2-ene]-1',2-dione
• CAS: 1426058-46-9
• 化学式: C₂₀H₂₄O₂
• 分子量: 296.409
• InChiKey: FORLYQGDAZRKBL-WOCWXWTJSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.1
• 重原子数：
  22
• 可旋转键数：
  1
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  34.1
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为产物：
  描述：

  (-)-curcusone B 在 1,8-二氮杂双环[5.4.0]十一碳-7-烯 作用下， 以 甲醇 为溶剂， 反应 20.0h， 以38%的产率得到(+)-spirocurcasone
  参考文献：
  名称：

  One-Step Semisynthesis Method of Spirocurcasone and Pyracurcasone from Curcusones A and B

  摘要：

  High contents of curcusones A and B and trace amounts of spirocurcasone exist in the roots of Jatropha curcas. Here, a one-step semisynthesis method of spirocurcasone and pyracurcasone was built, not only resulted an increased yield of spirocurcasone but also produced pyracurcasone, which exhibited greater cytotoxicity compared to curcusones A and B. The plausible mechanism of the formation of pyracurcasone was proposed, and the proposed biogenetic origin for spirocurcasone by Taglialatela-Scafati was confirmed.

  DOI：

  10.1021/ol500692j

文献信息

• Concise Total Synthesis of Spirocurcasone
  作者：Hideki Abe、Akimi Sato、Toyoharu Kobayashi、Hisanaka Ito

  DOI：10.1021/ol400228v

  日期：2013.3.15

  A concise total synthesis of spirocurcasone was accomplished. Key features of the synthesis involved a vinylogous Mukaiyama aldol reaction, a Carroll rearrangement of β-keto allyl ester derivative, an intramolecular aldol condensation, and a spiro ring formation by ring-closing metathesis of the pentaene compound. This synthetic work was complete in nine steps from (S)- or (R)-perillaldehyde without

  完成了螺环脲酮的简明全合成。合成的关键特征包括乙烯基的Mukaiyama羟醛反应，β-酮烯丙基烯丙基酯衍生物的Carroll重排，分子内羟醛缩合以及通过戊烯化合物的闭环易位形成螺环。在不使用保护基的情况下，由（S）-或（R）-紫苏醛分九步完成了该合成工作。有趣的是，合成螺环脲酮的旋光度不同于天然产物的报道值。
• Total Synthesis and Target Identification of the Curcusone Diterpenes
  作者：Chengsen Cui、Brendan G. Dwyer、Chang Liu、Daniel Abegg、Zhong-Jian Cai、Dominic G. Hoch、Xianglin Yin、Nan Qiu、Jie-Qing Liu、Alexander Adibekian、Mingji Dai

  DOI：10.1021/jacs.1c00557

  日期：2021.3.24

  study, no total synthesis of the curcusones was achieved and their anticancer mode of action remained unknown. Herein, we report our synthetic and chemoproteomics studies of the curcusone diterpenes which culminate in the first total synthesis of several curcusone natural products and identification of BRCA1-associated ATM activator 1 (BRAT1) as a cellular target. Our efficient synthesis is highly

  姜黄素天然产物是复杂的二萜类化合物，具有特征性的 [6-7-5] 三环碳骨架，类似于瑞香和tigliane二萜。其中，姜黄素 A-D 对广谱人类癌细胞系表现出有效的抗癌活性。在这项研究之前，没有实现姜黄酮的全合成，并且它们的抗癌作用方式仍然未知。在这里，我们报告了我们对姜黄素二萜的合成和化学蛋白质组学研究，这些研究最终导致了几种姜黄素天然产物的首次全合成和 BRCA1 相关 ATM 激活剂 1 (BRAT1) 作为细胞靶点的鉴定。我们的高效合成具有高度收敛性，以廉价和丰富的起始材料为基础，具有热 [3,3]-σ 重排和新型 FeCl 3- 促进级联反应快速构建姜黄酮关键环庚二烯酮核心，使我们首次全合成姜黄酮A和B只需要9步，C和D需要10步，二美草酮A需要12步。从姜黄酮 C 和 D 化学合成二美草香酮 A 提供了直接证据来支持所提出的 Diels-Alder 二聚化和螯合消除生物合成途径
• [EN] CURCUSONE DITERPENOIDS AND USES THEREOF<br/>[FR] DITERPÉNOÏDES DE CURCUSONE ET LEURS UTILISATIONS
  申请人：PURDUE RESEARCH FOUNDATION

  公开号：WO2022072266A1

  公开（公告）日：2022-04-07

  The present disclosure provides the first asymmetric total synthesis and target identification of the curcusone natural products. The novel convergent synthesis is built upon a cheap and abundant chiral pool molecule (8) and features a thermal [3,3]-sigmatropic rearrangement and an FeCl3-promoted global hydrolysis/adol condensation cascade to rapidly construct the critical cycloheptadienone core. By performing chemoproteomics with the alkyne probe 37, we identified the previously "undruggable" oncogenic protein BRAT1 as a key cellular target of 1d. Furthermore, 1d inhibits BRAT1 in cancer cells, thereby reducing cancer cell migration, increasing susceptibility to DNA damage, and inducing chemosensitization to the approved drug etoposide. Compound 1d is the first known small-molecule inhibitor for BRAT1, a master regulator of the DDR and DNA repair. Composition matters and methods of uses are within the scope of this disclosure.

  本公开提供了curcusone天然产物的第一种不对称全合成和靶标鉴定。这种新颖的汇合合成是基于一种廉价和丰富的手性池分子（8）构建的，并具有热[3,3]-Sigmatropic重排和FeCl3促进的全局水解/Adol缩合级联反应，以快速构建关键的环庚二烯酮核心。通过使用炔基探针37进行化学蛋白质组学，我们确定了之前“无法治愈”的致癌蛋白BRAT1作为1d的关键细胞靶标。此外，1d在癌细胞中抑制BRAT1，从而减少癌细胞迁移，增加对DNA损伤的敏感性，并诱导对批准药物依托泊苷的化疗敏感性。化合物1d是BRAT1的第一种已知小分子抑制剂，是DDR和DNA修复的主要调节因子。本公开的范围包括组合物和使用方法。
• One-Step Semisynthesis Method of Spirocurcasone and Pyracurcasone from Curcusones A and B
  作者：Xu-Yang Li、Yuan-Feng Yang、Xing-Rong Peng、Ming-Ming Li、Liang-Qun Li、Xu Deng、Hong-Bo Qin、Jie-Qing Liu、Ming-Hua Qiu

  DOI：10.1021/ol500692j

  日期：2014.4.18

  High contents of curcusones A and B and trace amounts of spirocurcasone exist in the roots of Jatropha curcas. Here, a one-step semisynthesis method of spirocurcasone and pyracurcasone was built, not only resulted an increased yield of spirocurcasone but also produced pyracurcasone, which exhibited greater cytotoxicity compared to curcusones A and B. The plausible mechanism of the formation of pyracurcasone was proposed, and the proposed biogenetic origin for spirocurcasone by Taglialatela-Scafati was confirmed.