8,9-Dihydro-3,11-diisopropoxy-14-(3-isopropoxy-4-methoxyphenyl)-2,12-dimethoxy-6H-[1]benzopyrano[4',3':4,5]pyrrolo[2,1-a]isoquinolin-6-one | 271243-11-9

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡咯
• 英文名称: 8,9-Dihydro-3,11-diisopropoxy-14-(3-isopropoxy-4-methoxyphenyl)-2,12-dimethoxy-6H-[1]benzopyrano[4',3':4,5]pyrrolo[2,1-a]isoquinolin-6-one
• 英文别名: 8,16-Dimethoxy-12-(4-methoxy-3-propan-2-yloxyphenyl)-7,17-di(propan-2-yloxy)-4-oxa-1-azapentacyclo[11.8.0.02,11.05,10.014,19]henicosa-2(11),5,7,9,12,14,16,18-octaen-3-one
• CAS: 271243-11-9
• 化学式: C₃₇H₄₁NO₈
• 分子量: 627.734
• InChiKey: SJQIELLRGSOZCF-UHFFFAOYSA-N

物化性质

• 熔点：
  206.5-207.5 °C(Solvent: Dichloromethane; Diethyl ether)
• 沸点：
  777.7±60.0 °C(predicted)
• 密度：
  1.25±0.1 g/cm3(Temp: 20 °C; Press: 760 Torr)(predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  7.6
• 重原子数：
  46
• 可旋转键数：
  10
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.38
• 拓扑面积：
  86.6
• 氢给体数：
  0
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  8,9-Dihydro-3,11-diisopropoxy-14-(3-isopropoxy-4-methoxyphenyl)-2,12-dimethoxy-6H-[1]benzopyrano[4',3':4,5]pyrrolo[2,1-a]isoquinolin-6-one 在 三氯化硼 作用下， 以 正庚烷 、 二氯甲烷 为溶剂， 以98%的产率得到lamellarin L
  参考文献：
  名称：

  薄片蛋白D，L和N的全合成

  摘要：

  通过使用Hinsberg型吡咯合成法和钯催化的3,4-二羟基吡咯二酚6的Suzuki-Miyaura偶联，已经完成了细胞毒性海洋生物碱，薄片蛋白D，L和N的总合成。普通中间体6的层状蛋白D，L和N的总产率分别为54％，58％和50％。

  DOI：

  10.1016/j.tet.2005.10.014
• 作为产物：
  描述：

  2,4-二溴苯甲醚 在 palladium diacetate 、 四(三苯基膦)钯 氢氧化钾 、 正丁基锂 、 叔丁基锂 、 sodium carbonate 、 potassium carbonate 作用下， 以 四氢呋喃 、 乙醚 、 乙醇 、 正己烷 、 水 、 二甲基亚砜 、 乙腈 、 正戊烷 为溶剂， 反应 59.0h， 生成 8,9-Dihydro-3,11-diisopropoxy-14-(3-isopropoxy-4-methoxyphenyl)-2,12-dimethoxy-6H-[1]benzopyrano[4',3':4,5]pyrrolo[2,1-a]isoquinolin-6-one
  参考文献：
  名称：

  薄片蛋白D，L和N的全合成

  摘要：

  通过使用Hinsberg型吡咯合成法和钯催化的3,4-二羟基吡咯二酚6的Suzuki-Miyaura偶联，已经完成了细胞毒性海洋生物碱，薄片蛋白D，L和N的总合成。普通中间体6的层状蛋白D，L和N的总产率分别为54％，58％和50％。

  DOI：

  10.1016/j.tet.2005.10.014

文献信息

• A Synthesis of Lamellarins via Regioselective Assembly of 1,2,3-Differentially Substituted 5,6-Dihydropyrrolo[2,1-a]Isoquinoline Core
  作者：Masatomo Iwao、Tsutomu Fukuda、Daichi Sato

  DOI：10.3987/com-15-13188

  日期：——

  the 5,6-dihydropyrrolo[2,1-a]isoquinoline core. The 1,2-diaryl-5,6-dihydropyrrolo[2,1-a]isoquinoline-3-carbaldehyde thus synthesized was readily converted to the lamellarin skeleton by mean of palladium-catalyzed oxidative lactonization. INTRODUCTION Lamellarins constitute an important class of natural products of marine origin. Since the first isolation of lamellarins A–D from Lamellaria sp. by Faulkner

  已经开发了海洋天然产物层状蛋白的模块化合成。使用的关键反应是 C3 选择性 Vilsmeier-Haack 甲酰化，然后是 5,6-二氢吡咯并[2,1-a]异喹啉核心的迭代溴化/交叉偶联。通过钯催化的氧化内酯化，由此合成的 1,2-二芳基-5,6-二氢吡咯并[2,1-a]异喹啉-3-甲醛很容易转化为层状蛋白骨架。引言 层状蛋白是一类重要的海洋天然产物。自从第一次从 Lamellaria sp. 中分离出层状蛋白 A-D。Faulkner 在 1985 年从海洋生物如被囊类动物、海绵和前鳃类中分离出了 50 多种层状蛋白（A-Z、α-χ、A1-A6 和 O1-O2，包括它们的乙酸盐和硫酸盐衍生物）。除了极少数例外，层状蛋白具有独特的 14-phenyl-6H-[1]benzopyrano[4',3':4,5]pyrrolo[2,1-a]isoquinolin-6-one 环系统（图 1）。此
• 10.1002/(sici)1521-3765(20000403)6:7<1147::aid-chem1147<3.3.co;2-t
  作者：Peschko, Christian、Winklhofer, Christian、Steglich, Wolfgang

  DOI：10.1002/(sici)1521-3765(20000403)6:7<1147::aid-chem1147<3.3.co;2-t

  日期：——
• Synthesis, Resolution, and Biological Evaluation of Atropisomeric (a<i>R</i>)- and (a<i>S</i>)-16-Methyllamellarins N: Unique Effects of the Axial Chirality on the Selectivity of Protein Kinases Inhibition
  作者：Kenyu Yoshida、Ryosuke Itoyama、Masashi Yamahira、Junji Tanaka、Nadège Loaëc、Olivier Lozach、Emilie Durieu、Tsutomu Fukuda、Fumito Ishibashi、Laurent Meijer、Masatomo Iwao

  DOI：10.1021/jm400719y

  日期：2013.9.26

  The total synthesis of the optically active (aR)- and (aS)-16-methyllamellarins N (3a and 3b) was achieved via resolution on HPLC chiral stationary phase. The kinase inhibitory activities of both enantiomers were evaluated on eight protein Icinases relevant to cancer and neurodegenerative diseases (CDKI/cyclin B, CDK2/cyclin A, CDK5/p25, GSK-3 alpha/beta, PIM1, DYRK1A, CLIO, and CK1). Isomer (aR)-3b exhibited potent but nonselective inhibition on all protein kinases except CK1, while (aS)-3a selectively inhibited only GSK-3 alpha/beta, PIM1, and DYRKIA. The different inhibition profiles of (aS)-3a and (aR)-3b were elucidated by docking simulation studies. Although parental lamellarin N (2) inhibited the action of topoisomerase I, both (aS)-3a and (aR)-3b showed no inhibition of this enzyme. The phenotypic scytotoxic activities of 2, (aS)-3a, and (aR)-3b on three cancer cell lines (HeLa, SH-SYSY, and IMR32) changed according to their topoisomerase I and protein kinase inhibitory activities.
• Total synthesis of lamellarins D, L, and N
  作者：Naotaka Fujikawa、Takeshi Ohta、Tomohiro Yamaguchi、Tsutomu Fukuda、Fumito Ishibashi、Masatomo Iwao

  DOI：10.1016/j.tet.2005.10.014

  日期：2006.1

  Total synthesis of cytotoxic marine alkaloids, lamellarins D, L, and N, has been achieved by using Hinsberg-type pyrrole synthesis and palladium-catalyzed Suzuki–Miyaura coupling of the 3,4-dihydroxypyrrole bistriflate 6 as the key reactions. The total yields of lamellarins D, L, and N from the common intermediate 6 are 54, 58, and 50%, respectively.

  通过使用Hinsberg型吡咯合成法和钯催化的3,4-二羟基吡咯二酚6的Suzuki-Miyaura偶联，已经完成了细胞毒性海洋生物碱，薄片蛋白D，L和N的总合成。普通中间体6的层状蛋白D，L和N的总产率分别为54％，58％和50％。
• Modular Synthesis of Lamellarins via Regioselective Assembly of 3,4,5-Differentially Arylated Pyrrole-2-carboxylates
  作者：Masashi Komatsubara、Teppei Umeki、Tsutomu Fukuda、Masatomo Iwao

  DOI：10.1021/jo402181w

  日期：2014.1.17

  A modular synthesis of lamellarins via 3,4,5-differentially arylated pyrrole-2-carboxylate intermediates has been developed. The key reactions employed are Br-Li exchange-methoxycarbonylation of 2,5-dibromo-1-(tert-butoxycarbonyl)-1H-pyrrole (1) followed by palladium-catalyzed iterative Suzuki-Miyaura coupling of the pyrrole core. The 3,4,5-triarylpyrrole 4 thus synthesized was readily converted to 5,6-saturated lamellarin L (2) and 5,6-unsaturated lamellarin N (3) via lactonization followed by annulation of the pyrrole nitrogen and lateral aromatic ring at C5 using 2-bromoethyl phenyl sulfide or bromoacetaldehyde dimethyl acetal as two-carbon homologation agents. In principle, this strategy allows the production of diverse lamellarins in short steps with high yields using readily accessible arylboronic acids as aromatic modules.