6-芳基茚并异喹啉酮衍生物的合成新方法
收稿日期: 2015-04-03
修回日期: 2015-04-27
网络出版日期: 2015-05-06
基金资助
国家自然科学基金(No. 81373279)、科技部“十二五”新药创制重大专项(No. 2012ZX09103101048)、江苏省科技支撑计划(No. BE2012745)和江苏省研究生科研创新计划(No. KYLX_0612)资助项目.
An Improved Synthesis of 6-Arylindenoisoquinoline Derivatives
Received date: 2015-04-03
Revised date: 2015-04-27
Online published: 2015-05-06
Supported by
Project supported by the National Natural Science Foundation of China (No. 81373279), the Twelfth Five-Year Plan Major Project of Candidate Drugs, Ministry of Science and Technology (No. 2012ZX09103101048), the Jiangsu Province Science and Technology Support Program of Social Development Project (No. BE2012745) and the Graduate Innovation Project of Jiangsu Province (No. KYLX_0612).
设计了6-芳基茚并异喹啉酮衍生物的合成新方法. 该方法运用立体选择性反应策略, 专一性地得到cis-中间体: cis-N-(4-羟基苯基)-1-氧代-3-苯基-1,2,3,4-四氢异喹啉-4-羧酸; 选择以KAl(SO4)2·12H2O为催化剂, 高酞酸、对氨基苯酚、苯甲醛三组分一锅法反应得到6-芳基茚并异喹啉酮母核, 最终以总收率36%～51%得到6-芳基茚并异喹啉酮衍生物, 比原方法的平均收率提高15%左右, 新方法具有立体选择性好、操作简化、收率高等优点, 适宜大量制备.
关键词： 6-芳基茚并异喹啉酮衍生物; 立体选择性反应; cis-中间体; 三组分一锅法; 合成
牛绍雄 , 唐智超 , 刘畅 , 王天麟 , 尤启冬 , 向华 . 6-芳基茚并异喹啉酮衍生物的合成新方法[J]. 有机化学, 2015 , 35(10) : 2150 -2156 . DOI: 10.6023/cjoc201504004
An improved process for the synthesis of 6-arylindenoisoquinoline derivatives was developed, and the key intermediate cis-N-(4-hydroxyphenyl)-1-oxo-3-phemyl-1,2,3,4-tetrahydroisoquinoline-4-carboxylic acid was stereoselectively synthesized. The intermediate with 6-arylindenoisoquinoline core could be obtained by an one-pot three-component condensation catalyzed by KAl(SO4)2·12H2O. The overall yield of the target compounds was 36%～51%. The improved synthesis method is more suitable for scale-up production with satisfactory stereoselectivity, easily purified procedures and higher yields.
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