Chin. J. Org. Chem. ›› 2015, Vol. 35 ›› Issue (10): 2150-2156.DOI: 10.6023/cjoc201504004 Previous Articles     Next Articles



牛绍雄a, 唐智超a, 刘畅c, 王天麟a, 尤启冬b, 向华a,b   

  1. a 中国药科大学药学院 江苏省药物分子设计与成药性优化重点实验室 南京 210009;
    b 中国药科大学药学院药物化学教研室 南京 210009;
    c 南京金陵中学 南京 210005
  • 收稿日期:2015-04-03 修回日期:2015-04-27 发布日期:2015-05-06
  • 通讯作者: 向华
  • 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

Niu Shaoxionga, Tang Zhichaoa, Liu Changc, Wang Tianlina, You Qidongb, Xiang Huaa,b   

  1. a Jiangsu Key Laboratory of Drug Design and Optimization, School of Pharmacy, China Pharmaceutical University, Nanjing 210009;
    b Department of Medicinal Chemistry, School of Pharmacy, China Pharmaceutical University, Nanjing 210009;
    c Jinling High School, Nanjing 210005
  • Received:2015-04-03 Revised:2015-04-27 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).

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.

Key words: 6-arylindenoisoquinolines, cis-intermediate, stereoselective reaction, one-pot three-component method, synthesis