((3S,4R)-4-(benzyloxy)-3,4-dihydroisoquinolin-3-yl)methanol | 1307770-71-3

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二氢异喹啉
• 英文名称: ((3S,4R)-4-(benzyloxy)-3,4-dihydroisoquinolin-3-yl)methanol
• 英文别名: [(3S,4R)-4-phenylmethoxy-3,4-dihydroisoquinolin-3-yl]methanol
• CAS: 1307770-71-3
• 化学式: C₁₇H₁₇NO₂
• 分子量: 267.327
• InChiKey: GMRJLSNPEVHPQH-DLBZAZTESA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.6
• 重原子数：
  20
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.24
• 拓扑面积：
  41.8
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  ((3S,4R)-4-(benzyloxy)-3,4-dihydroisoquinolin-3-yl)methanol 在 sodium tetrahydroborate 、 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 作用下， 以 乙醇 、 二氯甲烷 为溶剂， 反应 3.0h， 生成 N-((S)-1-((3S,4R)-4-(benzyloxy)-3-(hydroxymethyl)-3,4-dihydroisoquinolin-2(1H)-yl)-3-methyl-1-oxobutan-2-yl)-4-methylbenzenesulfonamide
  参考文献：
  名称：

  Design, synthesis and biological evaluations of chirally pure 1,2,3,4-tertrahydroisoquinoline analogs as anti-cancer agents

  摘要：

  A series of fifteen chiral 1,2,3,4-tetrahydroisoquinoline (THIQ) derivatives have been synthesized and their antiproliferative properties have been studied. The in vitro screening was performed against five cancer cell lines; MCF-7 (breast cancer), A549 (lung cancer), DU-145 (prostate cancer), Hela (cervical cancer) and HepG2 (liver cancer). Most of the compounds showed promising activity with IC50 Values ranging from 0.72 to 92.6 mu M. Among them, compounds 9a and 9b have shown significant activity against human prostate cancer cell line, i.e., DU-145 with IC50 value 0.72 and 1.23 mu M respectively. To investigate the mechanism of action, detailed biological studies of compounds 9a and 9b were carried out on the human prostate cancer cell line, DU-145. Flow cytometric analysis revealed that these compounds induced cell cycle arrest at G2/M phase. Tubulin polymerization assay and immunofluorescence analysis results suggested that these compounds effectively inhibit microtubule assembly formation in DU-145. The apoptosis inducing properties were evaluated by DNA fragmentation analysis, Caspase-3 activity assay, Annexin V-FITC assay and Western blot analysis of proapoptotic protein, Bax and antiapoptotic protein Bcl-2. (C) 2015 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2015.01.030
• 作为产物：
  描述：

  2-(2-溴苯基)-1,3-二恶烷 在 盐酸 、 碘 、 sodium hydride 、 magnesium 作用下， 以 四氢呋喃 、 水 、 N,N-二甲基甲酰胺 、 mineral oil 为溶剂， 反应 7.0h， 生成 ((3S,4R)-4-(benzyloxy)-3,4-dihydroisoquinolin-3-yl)methanol
  参考文献：
  名称：

  通过桥接的恶唑烷的Yb（OTf）3催化的非对映选择性开环合成高度取代的1,2,3,4-四氢异喹啉的合成路线：2-氮杂鬼臼毒素的不对称合成

  摘要：

  我们在此报告了一种从Garner醛向高度官能化的对映纯1,2,3,4-四氢异喹啉（THIQs）的稳健而有效的合成途径。我们通过1,2-和1,3- / 1,4-不对称诱导利用Garner醛的固有手性来迭代获得1,2,3,4-四取代的THIQ，这些化合物使用刚性且可分离的桥接恶唑烷，无需任何外部手性来源。从L-和D-加纳尔醛中高效合成了桥接的恶唑啉二烯的所有可能的立体异构体，并在Yb（OTf）3存在的情况下，通过与各种亲核试剂的非对映选择性开环将其转化为功能完全的THIQ。尽管在芳基环上具有取代基的电子性质，该方法仍提供了1,2,3,4-四取代的THIQ的八种可能的非对映异构体中的四种。最终，使用该合成路线从D- Garner醛中获得了2-氮杂鬼臼毒素的对映选择性合成，总收率为35.4％（八步）。

  DOI：

  10.1002/chem.201002938

文献信息

• Stereoselective synthesis of functionalized 1,2,3,4-tetrahydroisoquinolines (THIQs) via highly diastereoselective Ugi three-component reactions (U3CRs) with chiral 3,4-dihydroisoquinolines (DHIQs)
  作者：T. Ramanivas、G. Gayatri、D. Priyanka、V. L. Nayak、K. K. Singarapu、A. K. Srivastava

  DOI：10.1039/c5ra11144g

  日期：——

  A highly diastereoselective Ugi three-component reaction (U3CR) of chiral 3,4-dihydroisoquinolines has been developed to synthesize enantiopure 1,2,3,4-tetrahydroisoquinolines (THIQs).

  已开发出高度对映选择性的手性3,4-二氢异喹啉Ugi三组分反应（U3CR），用于合成对映纯的1,2,3,4-四氢异喹啉（THIQs）。
• Design, synthesis and biological evaluations of chirally pure 1,2,3,4-tertrahydroisoquinoline analogs as anti-cancer agents
  作者：Triparagiri Ramanivas、Bottu Sushma、V. Lakshma Nayak、Kunta Chandra Shekar、Ajay Kumar Srivastava

  DOI：10.1016/j.ejmech.2015.01.030

  日期：2015.3

  A series of fifteen chiral 1,2,3,4-tetrahydroisoquinoline (THIQ) derivatives have been synthesized and their antiproliferative properties have been studied. The in vitro screening was performed against five cancer cell lines; MCF-7 (breast cancer), A549 (lung cancer), DU-145 (prostate cancer), Hela (cervical cancer) and HepG2 (liver cancer). Most of the compounds showed promising activity with IC50 Values ranging from 0.72 to 92.6 mu M. Among them, compounds 9a and 9b have shown significant activity against human prostate cancer cell line, i.e., DU-145 with IC50 value 0.72 and 1.23 mu M respectively. To investigate the mechanism of action, detailed biological studies of compounds 9a and 9b were carried out on the human prostate cancer cell line, DU-145. Flow cytometric analysis revealed that these compounds induced cell cycle arrest at G2/M phase. Tubulin polymerization assay and immunofluorescence analysis results suggested that these compounds effectively inhibit microtubule assembly formation in DU-145. The apoptosis inducing properties were evaluated by DNA fragmentation analysis, Caspase-3 activity assay, Annexin V-FITC assay and Western blot analysis of proapoptotic protein, Bax and antiapoptotic protein Bcl-2. (C) 2015 Elsevier Masson SAS. All rights reserved.
• A Synthetic Route to Highly Substituted 1,2,3,4-Tetrahydroisoquinolines via Yb(OTf)3-Catalyzed Diastereoselective Ring Opening of Bridged Oxazolidines: Asymmetric Synthesis of 2-Azapodophyllotoxin
  作者：Ajay Kumar Srivastava、Minseob Koh、Seung Bum Park

  DOI：10.1002/chem.201002938

  日期：2011.4.18

  aldehydes and transformed into fully functionalized THIQs via diastereoselective ring opening with various nucleophiles in the presence of Yb(OTf)3. This methodology furnished four out of eight possible diastereomers of 1,2,3,4‐tetrasubstituted THIQs despite the electronic nature of substituents on the aryl rings. Finally, the enantioselective synthesis of 2‐azapodophyllotoxin was achieved with an overall

  我们在此报告了一种从Garner醛向高度官能化的对映纯1,2,3,4-四氢异喹啉（THIQs）的稳健而有效的合成途径。我们通过1,2-和1,3- / 1,4-不对称诱导利用Garner醛的固有手性来迭代获得1,2,3,4-四取代的THIQ，这些化合物使用刚性且可分离的桥接恶唑烷，无需任何外部手性来源。从L-和D-加纳尔醛中高效合成了桥接的恶唑啉二烯的所有可能的立体异构体，并在Yb（OTf）3存在的情况下，通过与各种亲核试剂的非对映选择性开环将其转化为功能完全的THIQ。尽管在芳基环上具有取代基的电子性质，该方法仍提供了1,2,3,4-四取代的THIQ的八种可能的非对映异构体中的四种。最终，使用该合成路线从D- Garner醛中获得了2-氮杂鬼臼毒素的对映选择性合成，总收率为35.4％（八步）。