Chin. J. Org. Chem. ›› 2019, Vol. 39 ›› Issue (3): 771-777.DOI: 10.6023/cjoc201807043 Previous Articles     Next Articles



牛丽萍, 邢顺凯, 李小六, 陈华   

  1. 河北大学化学与环境科学学院 河北省化学生物学重点实验室 保定 071002
  • 收稿日期:2018-07-24 修回日期:2018-08-23 发布日期:2018-10-26
  • 通讯作者: 李小六, 陈华;
  • 基金资助:


Synthesis of the Fused Tetracyclic Thiazinan-4-one Derivatives and Their Anti-tumor Activitiy

Niu Liping, Xing Shunkai, Li Xiaoliu, Chen Hua   

  1. Key Laboratory of Chemical Biology of Hebei Province, College of Chemistry and Environmental Science, Hebei University, Baoding 071002
  • Received:2018-07-24 Revised:2018-08-23 Published:2018-10-26
  • Contact: 10.6023/cjoc201807043;
  • Supported by:

    Project supported by the National Natural Science Foundation of China (No. 21372060) and the Natural Science Fundation of Hebei Province (No. B2016201031).

The benzothiazin-4-one intermediates were prepared by the one-pot three-components condensation from the N-Boc-L-prolinal 1, amino acid ethyl/methyl ester hydrochlorides 2a~2d, and mercaptobenzoic acids 3a~3b. After removal of Boc, the target novel fused tetracyclic thiazinan-4-one derivatives 6~11 were afforded by the intramolecular cyclo-amidation reaction. The absolute configurations of the newly generated chiral carbon (1-C) were determined by the coupling constants of H-1 and H-2 and the X-ray crystallographic structures. The tetracyclic alkaloids were examined for their anti-proliferative activity against Hela and A549 tumor cells. The results showed that some compounds could moderately inhibit the growth of Hela cells, and among them, (13aR,13bR) -1,2,3,13b-tetrahydrobenzo[e]pyrrolo[2',1':3,4]pyrazino[2,1-b] [1,3]thiazine-5,8(6H,13aH) -dione (6b) was the best one with the IC50 value of 9.50 μmol/L. However, all the compounds showed no anti-tumor activity against A549.

Key words: fused heterocyclic derivatives, thiazinan-4-one, three-components condensation, cyclo-amidation, anti-tumor activity