Citation: Niu Liping, Xing Shunkai, Li Xiaoliu, Chen Hua. Synthesis of the Fused Tetracyclic Thiazinan-4-one Derivatives and Their Anti-tumor Activitiy[J]. Chinese Journal of Organic Chemistry, ;2019, 39(3): 771-777. doi: 10.6023/cjoc201807043 shu

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

Key Laboratory of Chemical Biology of Hebei Province, College of Chemistry and Environmental Science, Hebei University, Baoding 071002

Corresponding author: Li Xiaoliu, lixl@hbu.cn Chen Hua, hua-todd@163.com
Received Date: 24 July 2018
Revised Date: 23 August 2018
Available Online: 26 March 2018
Fund Project: the Natural Science Fundation of Hebei Province B2016201031Project supported by the National Natural Science Foundation of China (No. 21372060) and the Natural Science Fundation of Hebei Province (No. B2016201031)the National Natural Science Foundation of China 21372060

Figures(5)

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.
- fused heterocyclic derivatives,
- thiazinan-4-one,
- three-components condensation,
- cyclo-amidation,
- anti-tumor activity
1. [1]
  Kim, J.; Movassaghi, M. Acc. Chem. Res. 2015, 48, 1159. doi: 10.1021/ar500454v
2. [2]
  Amit Kumar Chattopadhyay, A. K.; Hanessian, S. Chem. Rev. 2017, 117, 4104. doi: 10.1021/acs.chemrev.6b00412
3. [3]
  Chrzanowska, M.; Grajewska, A.; Rozwadowska, M. D. Chem. Rev. 2016, 116, 12369. doi: 10.1021/acs.chemrev.6b00315
4. [4]
  Zi, W. W.; Zuo, Z. W.; Ma, D. W. Acc. Chem. Res. 2015, 48, 702. doi: 10.1021/ar5004303
5. [5]
  Tripathi, A. C.; Gupta, S. J.; Fatima, G. N.; Sonar, P. K.; Verma, A.; Saraf, S. K. Eur. J. Med. Chem. 2014, 72, 52. doi: 10.1016/j.ejmech.2013.11.017
6. [6]
  Zarghi, A.; Zebardast, T.; Daraie, B.; Hedayati, M. Bioorg. Med. Chem. 2009, 17, 5369. doi: 10.1016/j.bmc.2009.06.056
7. [7]
  Geng, J. H.; Li, Y. X.; Zhang, W. J.; Su, X.; Guo, C. J. Shenyang Pharm. Univ. 2012, 29, 834(in Chinese).
8. [8]
  Tiwari, R.; Moraski, G. C.; Krchňάk, V.; Miller, P. A.; Colon-Martinez, M.; Herrero, E.; Oliver, A. G.; Miller, M. J. J. Am. Chem. Soc. 2013, 135, 3539. doi: 10.1021/ja311058q
9. [9]
  Cao, X.; Wang, S. B.; Deng, X. Q.; Liu, D. C.; Quan, Z. S. Med. Chem. Res. 2014, 23, 1829. doi: 10.1007/s00044-013-0778-y
10. [10]
  Feng, J. N.; Li, X. H.; Shao, J.; Zhu, M.; Li, Y.; Chen, H.; Li, X. L. Chin. J. Org. Chem. 2015, 35, 1370(in Chinese).
11. [11]
  Stössel, A.; Schlenk, M.; Hinz, S.; Küppers, P.; Heer, J.; Gütschow, M.; Müller, C. E. J. Med. Chem. 2013, 56, 4580. doi: 10.1021/jm400336x
12. [12]
  Bates, R. W. Tetrahedron Lett. 2018, 59, 559. doi: 10.1016/j.tetlet.2017.12.026
13. [13]
  Xiong, Y. X.; Huang, Z. S.; Tan, J. H. Eur. J. Med. Chem. 2015, 97, 538. doi: 10.1016/j.ejmech.2014.11.021
14. [14]
  Manjal, S. K.; Kaur, R.; Bhatia, R.; Kumar, K.; Singh, V.; Shankar, R.; Kaur, R.; Rawal, R. K. Bioorg. Chem. 2017, 75, 406. doi: 10.1016/j.bioorg.2017.10.014
15. [15]
  Shao, J.; Zhu, M.; Gao, L. G.; Chen, H.; Li, X. L. Carbohydr. Res. 2018, 456, 45. doi: 10.1016/j.carres.2017.12.005
16. [16]
  Yin, Z. Q.; Zhu, M.; Wei, S. N.; Shao, J.; Hou, Y. H.; Chen, H.; Li, X. L. Bioorg. Med. Chem. Lett. 2016, 26, 1738. doi: 10.1016/j.bmcl.2016.02.049
17. [17]
  Chen, H.; Shao, J.; Zhu, M.; Li, X. L. Chin. J. Org. Chem. 2016, 36, 527(in Chinese).
18. [18]
  Jain, A. K.; Vaidya, A.; Ravichandran, V.; Kashaw, S. K.; Agrawal, R. K. Bioorg. Med. Chem. 2012, 20, 3378. doi: 10.1016/j.bmc.2012.03.069
19. [19]
  Chen, H.; Yin, Q. M.; Li, C. X.; Wang, E. K.; Gao, F.; Zhang, X. B.; Yin, Z.; Wei, S. N.; Li, X. L.; Meng, M.; Zhang, P. Z.; Li, N.; Zhang, J. C. ACS Med. Chem. Lett. 2011, 2, 845. doi: 10.1021/ml200155k
20. [20]
  Chen, H.; Bai, J.; Jiao, L. L.; Guo, Z. H.; Yin, Q. M.; Li, X. L. Bioorg. Med. Chem. 2009, 17, 3980. doi: 10.1016/j.bmc.2009.04.024
21. [21]
  CCDC-1857715 for 10a and CCDC-1857714 for 11b contain the supplementary crystallographic data for this paper. These data can be obtained free of charge from The Cambridge Crystallographic Data Centre via www.ccdc.cam.ac.uk/data_request/cif.
22. [22]
  Mosmann, T. J. Immunol. Methods 1983, 65, 55. doi: 10.1016/0022-1759(83)90303-4
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