Indole[2,1-α]isoquinolines are an important class of bioactive molecules and show good antibacterial activity.In the present study,an efficient copper(I)-catalyzed acylation/cyclization has been developed for the con...Indole[2,1-α]isoquinolines are an important class of bioactive molecules and show good antibacterial activity.In the present study,an efficient copper(I)-catalyzed acylation/cyclization has been developed for the construction of indolo[2,1-α]isoquinoline derivatives by utilizing 2-aryl-N-acryloyl indole and benzohydrazide as reactants in the presence of CuI as catalyst and tert-butyl hydroperoxide as oxidant.The present protocol exhibits good functional group tolerance,and a series of acylated indole[2,1-α]isoquinolines were synthesized in moderate to good yields.Radical trapping experiments indicated that the reaction may involve a radical process.展开更多
Mechanistic studies of the cleavage and transformation of unactivated C_(sp3)-H bonds are a significant field of chemistry.Overcoming the inherent low acidity of C-H bonds to activate the inert substrates is challenge...Mechanistic studies of the cleavage and transformation of unactivated C_(sp3)-H bonds are a significant field of chemistry.Overcoming the inherent low acidity of C-H bonds to activate the inert substrates is challenge under mild conditions.And their complex multi-step transformations may also hinder mechanistic understanding.Herein,we perform theoretical calculations and experimental studies to explore the C_(sp3)-H bonds activation and acylation mechanisms of toluene/thioether using the relatively weak base LDA.A synergistic"main and auxiliary"model was revealed involving dual lithium metal by LDA dimers,and the aryl dilithium species as an intermediate base can facilitate C_(sp3)-H activation.This model not only aids in understanding the acidity of unactivated C_(sp3)-H bonds and the nucleophilicity of their conjugate bases for their kinetic control through cooperative interactions,but also predicts unusual kinetic isotope effects(KIE)for newly designed 2-(methylthio)naphthalene that are experimentally validated.This research is expected to provide a crucial scenario for the cleavage and transformation of unactivated C_(sp3)-H bonds and the development of new functionalities for alkali metal reagents.展开更多
目的检测酰基辅酶A合成酶长链家族成员1(Acyl-CoA synthetase long-chain family member 1,ACSL1)在喉癌组织中的表达情况,其对喉癌细胞生长、转移的影响及其具体作用机制。方法采用免疫印迹和实时荧光定量逆转录聚合酶链反应(qRT-PCR)...目的检测酰基辅酶A合成酶长链家族成员1(Acyl-CoA synthetase long-chain family member 1,ACSL1)在喉癌组织中的表达情况,其对喉癌细胞生长、转移的影响及其具体作用机制。方法采用免疫印迹和实时荧光定量逆转录聚合酶链反应(qRT-PCR)方法检测ACSL1在喉癌组织和癌旁组织中的表达。将喉癌细胞分为对照组和ACSL1过表达组,分别应用CCK-8和EdU法检测细胞活力和增殖能力,应用划痕实验检测细胞迁移,Transwell小室实验检测细胞侵袭,qRT-PCR、免疫印迹和细胞免疫荧光评估β-catenin的表达水平及其位置,ATP检测细胞内ATP表达水平。结果喉癌组织中ACSL1 mRNA和蛋白表达水平均较癌旁组织明显升高(P<0.05)。过表达ACSL1后,Hep-2细胞活力和增殖能力明显增加,细胞迁移和侵袭能力显著提高(P<0.01),同时增加细胞中β-catenin的活性和ATP含量。结论喉癌组织中ACSL1的表达升高。喉癌细胞中ACSL1可通过提高β-catenin的活性和ATP水平从而促进细胞的生长和转移,增加喉癌的恶性特征。展开更多
文摘Indole[2,1-α]isoquinolines are an important class of bioactive molecules and show good antibacterial activity.In the present study,an efficient copper(I)-catalyzed acylation/cyclization has been developed for the construction of indolo[2,1-α]isoquinoline derivatives by utilizing 2-aryl-N-acryloyl indole and benzohydrazide as reactants in the presence of CuI as catalyst and tert-butyl hydroperoxide as oxidant.The present protocol exhibits good functional group tolerance,and a series of acylated indole[2,1-α]isoquinolines were synthesized in moderate to good yields.Radical trapping experiments indicated that the reaction may involve a radical process.
基金the National Key Research and Development Program of China(No.2021YFA1500100)the National Natural Science Foundation of China(Nos.92156017 and 21890722)+1 种基金“Frontiers Science Center for New Organic Matter”,Nankai University(No.63181206)Haihe Laboratory of Sustainable Chemical Transformation of Tianjin(No.24HHWCSS00019)for generous financial support。
文摘Mechanistic studies of the cleavage and transformation of unactivated C_(sp3)-H bonds are a significant field of chemistry.Overcoming the inherent low acidity of C-H bonds to activate the inert substrates is challenge under mild conditions.And their complex multi-step transformations may also hinder mechanistic understanding.Herein,we perform theoretical calculations and experimental studies to explore the C_(sp3)-H bonds activation and acylation mechanisms of toluene/thioether using the relatively weak base LDA.A synergistic"main and auxiliary"model was revealed involving dual lithium metal by LDA dimers,and the aryl dilithium species as an intermediate base can facilitate C_(sp3)-H activation.This model not only aids in understanding the acidity of unactivated C_(sp3)-H bonds and the nucleophilicity of their conjugate bases for their kinetic control through cooperative interactions,but also predicts unusual kinetic isotope effects(KIE)for newly designed 2-(methylthio)naphthalene that are experimentally validated.This research is expected to provide a crucial scenario for the cleavage and transformation of unactivated C_(sp3)-H bonds and the development of new functionalities for alkali metal reagents.
文摘目的检测酰基辅酶A合成酶长链家族成员1(Acyl-CoA synthetase long-chain family member 1,ACSL1)在喉癌组织中的表达情况,其对喉癌细胞生长、转移的影响及其具体作用机制。方法采用免疫印迹和实时荧光定量逆转录聚合酶链反应(qRT-PCR)方法检测ACSL1在喉癌组织和癌旁组织中的表达。将喉癌细胞分为对照组和ACSL1过表达组,分别应用CCK-8和EdU法检测细胞活力和增殖能力,应用划痕实验检测细胞迁移,Transwell小室实验检测细胞侵袭,qRT-PCR、免疫印迹和细胞免疫荧光评估β-catenin的表达水平及其位置,ATP检测细胞内ATP表达水平。结果喉癌组织中ACSL1 mRNA和蛋白表达水平均较癌旁组织明显升高(P<0.05)。过表达ACSL1后,Hep-2细胞活力和增殖能力明显增加,细胞迁移和侵袭能力显著提高(P<0.01),同时增加细胞中β-catenin的活性和ATP含量。结论喉癌组织中ACSL1的表达升高。喉癌细胞中ACSL1可通过提高β-catenin的活性和ATP水平从而促进细胞的生长和转移,增加喉癌的恶性特征。
