14-(3,4-dimethoxyphenyl)-3-hydroxy-2,11,12-trimethoxy-8,9-dihydro-6H-chromeno[4',3':4,5]pyrrolo[2,1-a]isoquinolin-6-one | 858520-89-5

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡咯
• 英文名称: 14-(3,4-dimethoxyphenyl)-3-hydroxy-2,11,12-trimethoxy-8,9-dihydro-6H-chromeno[4',3':4,5]pyrrolo[2,1-a]isoquinolin-6-one
• 英文别名: dihydrolamellarin η；dehydrolam η；lamellarin-J；12-(3,4-dimethoxyphenyl)-7-hydroxy-8,16,17-trimethoxy-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: 858520-89-5
• 化学式: C₃₀H₂₇NO₈
• 分子量: 529.546
• InChiKey: YHRLGYIZMSRKSI-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.9
• 重原子数：
  39
• 可旋转键数：
  6
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.23
• 拓扑面积：
  97.6
• 氢给体数：
  1
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  14-(3,4-dimethoxyphenyl)-3-hydroxy-2,11,12-trimethoxy-8,9-dihydro-6H-chromeno[4',3':4,5]pyrrolo[2,1-a]isoquinolin-6-one 在 4-二甲氨基吡啶 、 氢氧化钾 、 三乙胺 、 2,3-二氯-5,6-二氰基-1,4-苯醌 作用下， 以 乙醇 、 二氯甲烷 为溶剂， 反应 4.0h， 生成 14-(3,4-dimethoxyphenyl)-3-hydroxy-2,11,12-trimethoxy-6H-[1]benzopyrano[4',3':4,5]pyrrolo-[2,1-a]isoquinolin-6-one
  参考文献：
  名称：

  Total Synthesis of Natural and Unnatural Lamellarins with Saturated and Unsaturated D-Rings

  摘要：

  Twenty-eight natural and unnatural lamellarins with either a saturated or an unsaturated D-ring were synthesized according to our developed synthetic route. The key step involved the Michael addition/ring closure (Mi-RC) of the benzyldihydroisoquinoline and alpha-nitrocinnamate derivatives, which provided the 2-carboethoxypyrrole intermediates in moderate to good yields (up to 78% yield). Subsequent hydrogenolysis/lactonization furnished lamellarins with a saturated D-ring in excellent yields (up to 93% yield). DDQ oxidation of the saturated lamellarin acetates led directly to the corresponding unsaturated analogues in 54-95% yield. In addition, only two steps in our developed strategy require column chromatography.

  DOI：

  10.1021/jo061810h
• 作为产物：
  描述：

  3,4-二甲氧基苯乙酸 在 palladium on activated charcoal 草酰氯 、 氢气 、 sodium hydride 、 碳酸氢钠 、 sodium carbonate 、 N,N-二甲基甲酰胺 、 三氯氧磷 作用下， 以 四氢呋喃 、 二氯甲烷 、 水 、 乙酸乙酯 、 N,N-二甲基甲酰胺 、 乙腈 为溶剂， 20.0 ℃ 、517.11 kPa 条件下， 反应 25.0h， 生成 14-(3,4-dimethoxyphenyl)-3-hydroxy-2,11,12-trimethoxy-8,9-dihydro-6H-chromeno[4',3':4,5]pyrrolo[2,1-a]isoquinolin-6-one
  参考文献：
  名称：

  Total Synthesis of Natural and Unnatural Lamellarins with Saturated and Unsaturated D-Rings

  摘要：

  Twenty-eight natural and unnatural lamellarins with either a saturated or an unsaturated D-ring were synthesized according to our developed synthetic route. The key step involved the Michael addition/ring closure (Mi-RC) of the benzyldihydroisoquinoline and alpha-nitrocinnamate derivatives, which provided the 2-carboethoxypyrrole intermediates in moderate to good yields (up to 78% yield). Subsequent hydrogenolysis/lactonization furnished lamellarins with a saturated D-ring in excellent yields (up to 93% yield). DDQ oxidation of the saturated lamellarin acetates led directly to the corresponding unsaturated analogues in 54-95% yield. In addition, only two steps in our developed strategy require column chromatography.

  DOI：

  10.1021/jo061810h

文献信息

• A High-Yielding Modular Access to the Lamellarins: Synthesis of Lamellarin G Trimethyl Ether, Lamellarin η and Dihydrolamellarin η
  作者：Dennis Imbri、Johannes Tauber、Till Opatz

  DOI：10.1002/chem.201303563

  日期：2013.11.4

  A deprotonated α‐aminonitrile serves as a key intermediate in a highly efficient (95 % per step on average; see scheme) modular synthetic approach to the lamellarin alkaloids. Its reaction with an α,β‐unsaturated aldehyde forms the central pyrrole ring in a one‐pot procedure. The construction of the fused pentacyclic skeleton is completed by a microwave‐assisted Ullmann‐type lactone formation.

  去质子化的α-氨基腈是薄片状生物碱高效模块化合成方法的关键中间体（平均每步95％;参见方案）。它与α，β-不饱和醛的反应在一锅法中形成了中心吡咯环。微波辅助的Ullmann型内酯的形成完成了稠合五环骨架的构建。
• Scalable Total Syntheses of Some Natural and Unnatural Lamellarins: Application of a One-Pot Domino Process for Regioselective Access to the Central 1,2,4-Trisubstituted Pyrrole Core
  作者：Virendra Kumar、Annapurna Awasthi、Abdus Salam、Tabrez Khan

  DOI：10.1021/acs.joc.9b01521

  日期：2019.9.20

  Short and scalable total syntheses of lamellarin G trimethyl ether, lamellarin D trimethyl ether, lamellarin H, lamellarin η, dihydrolamellarin η, and lamellarin U have been realized in four to six linear steps with an overall yield of ≤22%. Highlights of the synthesis include single-step access to the central 1,2,4-trisubstituted pyrrole core in a highly regioselective manner via a one-pot [3+2]

  lamellarin G三甲基醚，lamellarin D三甲基醚，lamellarin H，lamellarinη，二氢lamellarinη和lamellarin U的短而可扩展的总合成已通过四至六个线性步骤实现，总收率≤22％。合成的重点包括通过基于一锅[3 + 2]环加成/消除/芳香化序列的多米诺法，以高度区域选择性的方式一步一步进入中心1,2,4-三取代的吡咯核心。随后，在单锅操作中，钯介导的双CH氧化双偶联提供了层状蛋白中存在的五环香豆素融合的吡咯并二氢异喹啉核心的通道。
• Utility of Polymer-Supported Reagents in the Total Synthesis of Lamellarins
  作者：Poonsakdi Ploypradith、Rachel Kirk Kagan、Somsak Ruchirawat

  DOI：10.1021/jo050388m

  日期：2005.6.1

  Four solid-supported reagents have been utilized in the multistep synthesis of lamellarins. The use of Amberlyst A-26 Br-3(-) and polymer bound pyridine hydrobromide perbromide (PVPHP) for keto alpha-bromination of the less studied ortho-substituted acetophenone derivatives selectively furnished the corresponding monobromination products (phenacyl bromide derivatives), which were used directly in condensation reactions with benzyldihydroisoquinoline mediated by Amberlyst A-26 NaCO3-. The 2H-pyrrole carbonates subsequently underwent intramolecular Friedel-Crafts transacylation followed by lactonization to provide the lamellarin skeleton. Alternatively, Amberlyst A-26 NaCO3- effectively served as base in condensation reaction of benzyldihydroisoquinoline with alpha-nitrocinnamate derivatives to provide the corresponding 2-ethoxycarbonyl pyrroles, which smoothly underwent O-debenzylation reaction followed by lactonization to furnish the lamellarin skeleton. The novel Amberlyst-15 mediated lactonization reactions effectively combined the otherwise two separate steps into a single transformation.