3-(benzyloxy)-4-methoxy-5-methylbenzaldehyde | 575444-12-1

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: 3-(benzyloxy)-4-methoxy-5-methylbenzaldehyde
• 英文别名: 3-benzyloxy-4-methoxy-5-methylbenzaldehyde；4-methoxy-3-methyl-5-phenylmethoxybenzaldehyde
• CAS: 575444-12-1
• 化学式: C₁₆H₁₆O₃
• 分子量: 256.301
• InChiKey: SIUJTHPUNXGMSQ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.2
• 重原子数：
  19
• 可旋转键数：
  5
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.19
• 拓扑面积：
  35.5
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  3-(benzyloxy)-4-methoxy-5-methylbenzaldehyde 在 吡啶 、 甲醇 、 N-溴代丁二酰亚胺(NBS) 、 甲酸 、 (+)-1,2-bis-[(2S,5S)-2,5-diethylphospholano]benzene (1,5-cycloctadiene)rhodium(I) trifluoromethanesulfonate 、 10% Pd/C 、 水 、 氢气 、 二异丁基氢化铝 、 potassium carbonate 、 1-羟基苯并三唑 、 对甲苯磺酸 、 1,8-二氮杂双环[5.4.0]十一碳-7-烯 、 sodium sulfate 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 三乙胺 、 N,N-二异丙基乙胺 、 乙酰氯 、 三氟乙酸 、 2-巯基乙醇 、 lithium hydroxide 、 四甲基胍 作用下， 以 四氢呋喃 、 甲醇 、 二氯甲烷 、 乙酸乙酯 、 丙酮 、 甲苯 、 乙腈 为溶剂， -78.0~50.0 ℃ 、3.45 MPa 条件下， 反应 289.42h， 生成
  参考文献：
  名称：

  Synthetic Studies toward Ecteinascidin 743 (Trabectedin)

  摘要：

  An alternative synthetic route to an intermediate in the synthesis of ecteinascidin 743 has been established by using a Pictet-Spengler reaction and a Friedel-Crafts type reaction.

  DOI：

  10.1055/s-0032-1316579
• 作为产物：
  描述：

  3-甲基苯邻二酚 在 碳酸氢钠 、 potassium carbonate 、 sodium iodide 作用下， 以 丙酮 、 乙腈 为溶剂， 反应 142.0h， 生成 3-(benzyloxy)-4-methoxy-5-methylbenzaldehyde
  参考文献：
  名称：

  Catalytic asymmetric synthesis of the common amino acid component in the biosynthesis of tetrahydroisoquinoline alkaloids

  摘要：

  Biosynthetic assembly lines of tetrahydroisoquinoline alkaloids employ the tyrosine derivative, (S)-2-amino-3-(3-hydroxy-4-methoxy-5-methylphenyl)propanoic acid, as a common amino acid building block. A catalytic asymmetric synthetic route to the common amino acid component has been developed by making use of Maruoka's chiral phase transfer alkylation of a glycine derivative with the requisite benzyl bromide. (C) 2015 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.tetlet.2015.12.110

文献信息

• Synthesis of (±)-phthalascidin 650 analogue: new synthetic route to (±)-phthalascidin 622
  作者：Christian R. Razafindrabe、Sylvain Aubry、Benjamin Bourdon、Marta Andriantsiferana、Stéphane Pellet-Rostaing、Marc Lemaire

  DOI：10.1016/j.tet.2010.08.053

  日期：2010.11

  synthesis of functionalized phenolic α-amino-alcohol (±)-13 as synthetic precursor of the catechol tetrahydroisoquinoline structure of phthalascidin 650 is disclosed. Starting from 3-methylcatechol 5, eight steps of synthesis give rise to the synthesis of phenolic α-amino-alcohol (±)-13 in 27% overall yield. This synthetic strategy involves the elaboration of fully functionalized aromatic aldehyde 8 and its

  公开了作为邻苯二酚650的邻苯二酚四氢异喹啉结构的合成前体的官能化酚类α-氨基醇（±）-13的合成。从3-甲基邻苯二酚5开始，八个合成步骤以27％的总收率合成了酚类α-氨基醇（±）-13。该合成策略涉及通过Knoevenagel缩合，完全还原硝基烯酮和酯官能团以及对苄基保护基进行氢解，对完全官能化的芳族醛8进行精制并将其转化为酚类α-氨基醇（±）-13。五环（±）-18在另外四个步骤后获得。酚α氨基醇之间的的Pictet-格勒环化（±） - 13和ñ -保护的α氨基醛4允许获得（1,3'） -双-四氢异喹啉14与Ñ甲基化的和Ñ -Fmoc删除。最后一步是用于分子内缩合的Swern氧化法。
• Synthesis of (±)-phthalascidin 622
  作者：R. Razafindrabe Christian、Aubry Sylvain、Bourdon Benjamin、Andriantsiferana Marta、Pellet-Rostaing Stephane、Lemaire Marc

  DOI：10.1007/s11426-010-4075-z

  日期：2010.9

  synthesis of functionalized phenolic α-amino-alcohols (±)-8 and (±)-16 as synthetic precursors of the catechol tetrahydroisoquinoline structure of phthalascidin 650 was disclosed. (±)-8 was prepared in 5 steps from the commercially available sesamol. Starting from 3-methyl catechol 5, 8 steps gave rise to the synthesis of phenolic α-amino-alcohol (±)-16 in 27% overall yield. This synthetic strategy involved

  公开了作为邻苯二酚650的邻苯二酚四氢异喹啉结构的合成前体的官能化酚类α-氨基醇（±）-8和（±）-16的合成。（±） - 8是在5个步骤制备由市售芝麻酚。从3-甲基邻苯二酚5开始，经过8个步骤，以27％的总收率合成了酚类α-氨基醇（±）-16。该合成策略涉及对完全官能化的芳族醛13进行精细加工，并将其转化为酚类α-氨基醇（±）-16通过Knoevenagel缩合反应，同时还原硝基烯酮和酯官能团，以及苄基保护基的氢解。在另外4个步骤后获得了五环（±）-4。在酚类α-氨基醇（±）-16和N-保护的α-氨基醛4之间进行Pictet-Spengler环化反应，可以得到（1,3'）- N-甲基化和N-化的双-四氢异喹啉17 Fmoc已删除。最后一步是Swern氧化，可实现预期的分子内缩合。
• Synthetic studies on ecteinascidin 743: asymmetric synthesis of the versatile amino acid component
  作者：Wei Jin、Robert M Williams

  DOI：10.1016/s0040-4039(03)01082-7

  日期：2003.6

  The asymmetric synthesis of the modified tyrosine derivative as a basic building block for the ecteinascidin and safracin family of antitumor alkaloids has been achieved in nine steps and 39% overall yield.

  九个步骤实现了酪氨酸衍生物和safracin系列抗肿瘤生物碱的基本组成部分的修饰酪氨酸衍生物的不对称合成，总收率达39％。
• Akt/mTOR Targeting Activity of Resveratrol Derivatives in Non-Small Lung Cancer
  作者：Bhurichaya Innets、Sunisa Thongsom、Korrakod Petsri、Satapat Racha、Masashi Yokoya、Sohsuke Moriue、Chatchai Chaotham、Pithi Chanvorachote

  DOI：10.3390/molecules27238268

  日期：——

  The Akt-mTOR signal is important for the survival and proliferation of cancer cells and has become an interesting drug target. In this study, five resveratrol derivatives were evaluated for anticancer activity and Akt/mTOR targeting activity in non-small lung cancer cell lines. The effects of resveratrol derivatives on cell proliferation were assessed by 2,5-diphenyl-2H-tetrazolium bromide (MTT) assay, nucleus staining, and colony formation assay. Furthermore, the effect of resveratrol derivatives on proliferation-related protein expression was analyzed by immunofluorescence and Western blotting. For the structure–activity relationship (SAR), results reveal that two derivatives of resveratrol which are 4,4′-(ethane-1,2-diyl) bis(2-methoxyphenol) (RD2) and the 4-(3-hydroxy-4-methoxyphenethyl)-2-methoxyphenol (RD3) had very similar structures but exerted different cytotoxicity. The IC50 of RD2 and RD3 were 108.6 ± 10.82 and more than 200 µM in the A549 cell line and 103.5 ± 6.08 and more than 200 µM in H23 cells, respectively. RD2 inhibited cell proliferation and induced apoptosis when compared with the control, while RD3 caused minimal effects. Cells treated with RD2 exhibited apoptotic nuclei in a concomitant with the reduction of cellular p-Akt and p-mTOR. RD3 had minimal effects on such proteins. According to these results, molecular docking analysis revealed a high-affinity interaction between RD2 and an Akt molecule at the ATP-binding and the allosteric sites, indicating this RD2 as a potential Akt inhibitor. This study provides useful information of resveratrol derivatives RD2 for treating lung cancer via Akt/mTOR inhibition.

  Akt-mTOR信号通路对于癌细胞的生存和增殖至关重要，已成为一种有趣的药物靶点。本研究评估了五种白藜芦醇衍生物在非小细胞肺癌细胞系中的抗癌活性和对Akt/mTOR靶向作用的影响。通过2,5-二苯基-2H-四唑溴化物（MTT）试验、核染色和集落形成试验评估了白藜芦醇衍生物对细胞增殖的影响。此外，通过免疫荧光和Western blotting分析白藜芦醇衍生物对增殖相关蛋白表达的影响。结果显示，白藜芦醇的两种衍生物RD2和RD3结构非常相似，但表现出不同的细胞毒性。在A549细胞系中，RD2和RD3的IC50分别为108.6±10.82和大于200 µM，在H23细胞中，RD2和RD3的IC50分别为103.5±6.08和大于200 µM。与对照组相比，RD2抑制了细胞增殖并诱导了凋亡，而RD3的影响很小。RD2处理的细胞伴随着细胞内p-Akt和p-mTOR的降低而出现凋亡核。而RD3对这些蛋白的影响很小。分子对接分析表明，RD2与Akt分子在ATP结合和变构位点上具有高亲和力的相互作用，表明RD2是一种潜在的Akt抑制剂。本研究为通过Akt/mTOR抑制剂治疗肺癌提供了有用的信息，特别是白藜芦醇衍生物RD2。
• Catalytic asymmetric synthesis of the common amino acid component in the biosynthesis of tetrahydroisoquinoline alkaloids
  作者：Ryo Tanifuji、Hiroki Oguri、Kento Koketsu、Yuki Yoshinaga、Atsushi Minami、Hideaki Oikawa

  DOI：10.1016/j.tetlet.2015.12.110

  日期：2016.2

  Biosynthetic assembly lines of tetrahydroisoquinoline alkaloids employ the tyrosine derivative, (S)-2-amino-3-(3-hydroxy-4-methoxy-5-methylphenyl)propanoic acid, as a common amino acid building block. A catalytic asymmetric synthetic route to the common amino acid component has been developed by making use of Maruoka's chiral phase transfer alkylation of a glycine derivative with the requisite benzyl bromide. (C) 2015 Elsevier Ltd. All rights reserved.