以邻氨基苯甲酰胺(5)为原料,依次经分子间环合、烷基化、氨解和分子内环合四步反应成功合成目标化合物3,4-二氢-2H-吡嗪并[2,1-b]喹唑啉-1,6-二酮(10),总收率为46.5%,其中,中间体(8)、(9)及目标化合物(10)均未见文献报道,其结构经1 H NM...以邻氨基苯甲酰胺(5)为原料,依次经分子间环合、烷基化、氨解和分子内环合四步反应成功合成目标化合物3,4-二氢-2H-吡嗪并[2,1-b]喹唑啉-1,6-二酮(10),总收率为46.5%,其中,中间体(8)、(9)及目标化合物(10)均未见文献报道,其结构经1 H NMR和MS(ESI)确证,并采用MTT法初步评价目标化合物的体外抗肝癌活性。结果表明,3,4-二氢-2H-吡嗪并[2,1-b]喹唑啉-1,6-二酮对SMMC-7721具有明显的抑制活性,优于阳性对照药舒尼替尼,可为进一步发现新型抗肝癌药物提供先导结构,也为该类衍生物的大量合成和结构改造提供参考方法。展开更多
Although there is a growing interest in developing asymmetric 1,6-addition reactions of carbon nucleo-philes to Michael acceptors,the corresponding 1,6-addition of homoenolates remains an unsolved problem.Currently,th...Although there is a growing interest in developing asymmetric 1,6-addition reactions of carbon nucleo-philes to Michael acceptors,the corresponding 1,6-addition of homoenolates remains an unsolved problem.Currently,the N-heterocyclic carbene(NHC)-catalyzed cycloadditions of homoenolate equivalent intermediates have achieved widespread success.However,considerable limitations still exist for the linear reactions with electron-deficient alkenes,which are limited to 1,4-Michael acceptors.This report presents the first NHC-catalyzed asym-metric homoenolate addition of enals to 1,6-Michael acceptors.The strategy leads to the challenging nonspirocyclic 3,3-disubstituted oxindoles with two adjacent stereocenters,a quaternary and a trisubsti-tuted one,in good yields and high stereoselectivities with a wide variety of substrates.展开更多
文摘以邻氨基苯甲酰胺(5)为原料,依次经分子间环合、烷基化、氨解和分子内环合四步反应成功合成目标化合物3,4-二氢-2H-吡嗪并[2,1-b]喹唑啉-1,6-二酮(10),总收率为46.5%,其中,中间体(8)、(9)及目标化合物(10)均未见文献报道,其结构经1 H NMR和MS(ESI)确证,并采用MTT法初步评价目标化合物的体外抗肝癌活性。结果表明,3,4-二氢-2H-吡嗪并[2,1-b]喹唑啉-1,6-二酮对SMMC-7721具有明显的抑制活性,优于阳性对照药舒尼替尼,可为进一步发现新型抗肝癌药物提供先导结构,也为该类衍生物的大量合成和结构改造提供参考方法。
文摘Although there is a growing interest in developing asymmetric 1,6-addition reactions of carbon nucleo-philes to Michael acceptors,the corresponding 1,6-addition of homoenolates remains an unsolved problem.Currently,the N-heterocyclic carbene(NHC)-catalyzed cycloadditions of homoenolate equivalent intermediates have achieved widespread success.However,considerable limitations still exist for the linear reactions with electron-deficient alkenes,which are limited to 1,4-Michael acceptors.This report presents the first NHC-catalyzed asym-metric homoenolate addition of enals to 1,6-Michael acceptors.The strategy leads to the challenging nonspirocyclic 3,3-disubstituted oxindoles with two adjacent stereocenters,a quaternary and a trisubsti-tuted one,in good yields and high stereoselectivities with a wide variety of substrates.
