(3S)-3-(tert-butyldimethylsilyloxymethyl)-1,2,3,4-tetrahydroisoquinoline | 215928-81-7

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 四氢异喹啉
• 英文名称: (3S)-3-(tert-butyldimethylsilyloxymethyl)-1,2,3,4-tetrahydroisoquinoline
• 英文别名: (S)-3-(((tert-butyldimethylsilyl)oxy)methyl)-1,2,3,4-tetrahydroisoquinoline；(S)-3-((tert-butyldimethylsilyloxy)methyl)-1,2,3,4-tetrahydroisoquinoline；tert-butyl-dimethyl-[[(3S)-1,2,3,4-tetrahydroisoquinolin-3-yl]methoxy]silane
• CAS: 215928-81-7
• 化学式: C₁₆H₂₇NOSi
• 分子量: 277.482
• InChiKey: IVVWXEBVCUZISF-HNNXBMFYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.72
• 重原子数：
  19
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.62
• 拓扑面积：
  21.3
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  (3S)-3-(tert-butyldimethylsilyloxymethyl)-1,2,3,4-tetrahydroisoquinoline 在 盐酸 、 1-羟基苯并三唑 、 溶剂黄146 、 N,N-二异丙基乙胺 、 N,N'-二环己基碳二亚胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 26.0h， 生成 2-Amino-3-(4-hydroxy-2,6-dimethyl-phenyl)-1-(3-hydroxymethyl-3,4-dihydro-1H-isoquinolin-2-yl)-propan-1-one
  参考文献：
  名称：

  Novel C-Terminus Modifications of the Dmt-Tic Motif:  A New Class of Dipeptide Analogues Showing Altered Pharmacological Profiles Toward the Opioid Receptors

  摘要：

  The design, synthesis and pharmacological evaluation of a novel class of Dmt-Tic dipeptide analogues are described. These resulting analogues bearing different C-terminal functionalities were found to bind to the human delta receptor with high affinity. One specific class of dipeptides bearing urea/thiourea functionalities showed partial to full activation of the delta receptor. Several dipeptides also showed good binding affinities with full activation of the human kappa receptor, a novel property for those ligands.

  DOI：

  10.1021/jm015532k
• 作为产物：
  描述：

  N-叔丁氧羰基-(S)-1,2,3,4-四氢异喹啉-3-羧酸 在 N-甲基吗啉 、 盐酸 、 sodium tetrahydroborate 、 TEA 、 溶剂黄146 作用下， 以 乙二醇二甲醚 、 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 6.41h， 生成 (3S)-3-(tert-butyldimethylsilyloxymethyl)-1,2,3,4-tetrahydroisoquinoline
  参考文献：
  名称：

  Novel C-Terminus Modifications of the Dmt-Tic Motif:  A New Class of Dipeptide Analogues Showing Altered Pharmacological Profiles Toward the Opioid Receptors

  摘要：

  The design, synthesis and pharmacological evaluation of a novel class of Dmt-Tic dipeptide analogues are described. These resulting analogues bearing different C-terminal functionalities were found to bind to the human delta receptor with high affinity. One specific class of dipeptides bearing urea/thiourea functionalities showed partial to full activation of the delta receptor. Several dipeptides also showed good binding affinities with full activation of the human kappa receptor, a novel property for those ligands.

  DOI：

  10.1021/jm015532k

文献信息

• Design, Synthesis, and Structure–Activity Relationships of Novel Tetrahydroisoquinolino Benzodiazepine Dimer Antitumor Agents and Their Application in Antibody–Drug Conjugates
  作者：Naidu S. Chowdari、Yong Zhang、Ivar McDonald、Walter Johnson、David R. Langley、Prasanna Sivaprakasam、Robert Mate、Tram Huynh、Srikanth Kotapati、Madhura Deshpande、Chin Pan、Daniel Menezes、Yichong Wang、Chetana Rao、Ganapathy Sarma、Bethanne M. Warrack、Vangipuram S. Rangan、Sung Mei-Chen、Pina Cardarelli、Shrikant Deshpande、David Passmore、Richard Rampulla、Arvind Mathur、Robert Borzilleri、Arvind Rajpal、Gregory Vite、Sanjeev Gangwar

  DOI：10.1021/acs.jmedchem.0c01385

  日期：2020.11.25

  series of tetrahydroisoquinoline-based benzodiazepine dimers were synthesized and tested for in vitro cytotoxicity against a panel of cancer cell lines. Structure–activity relationship investigation of various spacers guided by molecular modeling studies helped to identify compounds with picomolar activity. Payload 17 was conjugated to anti-mesothelin and anti-fucosylated monosialotetrahexosylganglioside

  合成了一系列基于四氢异喹啉的苯并二氮杂二聚体，并测试了其对一组癌细胞系的体外细胞毒性。通过分子建模研究指导的各种间隔基的结构-活性关系研究有助于鉴定具有皮摩尔活性的化合物。有效负载17通过溶酶体可裂解的缬氨酸-瓜氨酸二肽接头，通过异源赖氨酸偶联和细菌转谷氨酰胺酶介导的位点特异性偶联，将其与抗间皮素和抗岩藻糖基化的单唾液酸四己糖基神经节苷脂（FucGM1）抗体偶联。在体外，这些抗体药物偶联物（ADC）对人类癌细胞系表现出显着的细胞毒性和靶标介导的选择性。在小鼠的胃癌和肺癌异种移植模型中，进一步评估了这些ADC的药代动力学和功效。在单剂量ADC- 46（0.02μmol / kg）之后，在这些模型中观察到一致的药代动力学特征，高靶标特异性和强大的抗肿瘤活性。
• Enantioselective deprotonation of 4-tert-butylcyclohexanone by conformationally constrained chiral lithium amide bases
  作者：Varinder K. Aggarwal、Paul S. Humphries、Ashley Fenwick

  DOI：10.1039/a905947d

  日期：——

  Conformationally rigid chiral lithium amides based on a tetrahydroisoquinoline motif have been prepared bearing a range of substituents at C1 and C3. These bases were tested in the asymmetric deprotonation reaction of 4-tert-butylcyclohexanone. Although the 1-substituted tetrahydroisoquinolines gave low enantioselectivity, the chiral bases containing a nitrogen heterocycle at C3 were found to induce

  已经制备了基于四氢异喹啉基序的构象刚性的手性锂酰胺，其在C1和C3处带有一系列取代基。在4-叔丁基环己酮的不对称去质子反应中测试了这些碱。尽管1-取代的四氢异喹啉具有较低的对映选择性，但发现在HMPA存在下，在C3处含有氮杂环的手性碱可诱导较高的对映选择性（81％ee）。
• Towards a Total Synthesis of Quinocarcin: Diastereoselective Synthesis of Functionalized Azepino[1,2-b]isoquinolines
  作者：Oliver Koepler、Sabine Laschat、Angelika Baro、Peter Fischer、Burkhard Miehlich、Marc Hotfilder、Christoph le Viseur

  DOI：10.1002/ejoc.200400231

  日期：2004.9

  corresponding 1-unsubstituted tetrahydroisoquinoline alcohol 11 were converted into aldehydes 27 and 33, which cyclized in the presence of different Lewis acids to give the substituted azepino[1,2-b]isoquinolines 34 and 35, respectively, which are key structural features of the alkaloid quinocarcin. The stereoselectivities of the Lewis-acid-catalyzed hetero-ene reaction are highly dependent on the substitution

  1,3-二取代的四氢-恶唑并异喹啉酮 19a、b 是通过卡特里茨基的苯并三唑方法从苯丙氨酸中分七步获得的，总产率为 42%。通过使用 LiBH4/MeOH 对酯基进行化学选择性还原，将三环恶唑烷酮 19a 进一步转化为氨基醇 10。化合物 10 和相应的 1-未取代的四氢异喹啉醇 11 被转化为醛 27 和 33，它们在不同的路易斯酸存在下环化，分别得到取代的氮杂[1,2-b] 异喹啉 34 和 35，这是关键生物碱喹诺酮的结构特征。路易斯酸催化的杂烯反应的立体选择性高度依赖于路易斯酸的取代模式和类型。(© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2004)
• Intermolecular Regio‐ and Stereoselective Hetero‐[5+2] Cycloaddition of Oxidopyrylium Ylides and Cyclic Imines
  作者：Changgui Zhao、Daniel A. Glazier、Daoshan Yang、Dan Yin、IIia A. Guzei、Michael M. Aristov、Peng Liu、Weiping Tang

  DOI：10.1002/anie.201811896

  日期：2019.1.14

  We have developed the first intermolecular hetero‐[5+2] cycloaddition reaction between oxidopyrylium ylides and cyclic imines with excellent control of regio‐ and stereoselectivity. Surprisingly, divergent stereochemistry was observed depending on the substitution pattern of the oxidopyrylium ylide. This new reaction provides quick access to highly substituted nitrogen‐containing seven‐membered rings—azepanes

  我们开发了第一个分子间异[5 + 2]环氧化吡啶鎓和环状亚胺之间的杂分子间[5 + 2]环加成反应，可很好地控制区域选择性和立体选择性。出乎意料的是，根据氧化吡啶鎓叶立德的取代模式观察到不同的立体化学。这种新的反应使人们可以快速进入高度取代的含氮七元环-氮杂环丁烷。值得注意的是，广泛的氧化吡啶鎓基团和环状亚胺参与了这种新型的异[5 + 2]环加成反应，并且环加合物可以轻松转化为生物活性天然产物的核心骨架。DFT计算表明，环加成反应通过逐步途径进行，亚胺氮原子充当亲核试剂以引发环加成反应。
• Stereoselective synthesis of 1,3-disubstituted dihydroisoquinolines <i>via</i><scp>l</scp>-phenylalanine-derived dihydroisoquinoline <i>N</i>-oxides
  作者：Jesús Flores-Ferrándiz、Nicholas Carter、Maria José González-Soria、Malgorzata Wasinska、Daniel Gill、Beatriz Maciá、Vittorio Caprio

  DOI：10.1039/c8ob02007h

  日期：——

  The preparation of chiral pool-derived nitrone 3 and its use in the protecting-group free, stereoselective synthesis of a range of 1,3-disubstituted tetrahydroisoquinolines is described. Grignard reagent additions to nitrone 3 yielded trans-1,3-disubstituted N-hydroxytetrahydroisoquinolines 6 with good levels of selectivity, while 1,3-dipolar cycloadditions to this nitrone provided access to 3-(2-

  描述了手性池衍生的硝酮3的制备及其在无保护基的立体选择性合成一系列1,3-二取代的四氢异喹啉中的用途。将格氏试剂添加到硝酮3中产生具有良好选择性的反式-1，3-二取代的N-羟基四氢异喹啉6，而向该硝酮的1，3-偶极环加成提供了作为单一非对映异构体的3-（2-羟基烷基）异喹啉12。