Advertisement

Chemical Papers

, Volume 64, Issue 4, pp 533–536 | Cite as

A novel, stereoselective and practical protocol for the synthesis of 4β-aminopodophyllotoxins

  • Ying-Qian Liu
  • Lin-Hai Li
  • Liu Yang
  • Hong-Yu LiEmail author
Short Communication

Abstract

Ritter reaction of podophyllotoxins with chloroacetonitrile and subsequent cleavage of the chloroacetyl group in the resulting chloroacetamide with thiourea under both classical heating and ultrasonic conditions is an efficient procedure for the synthesis of 4β-aminopodophyllotoxins. In general, significant improvements in the rates of reaction and yields of the sonochemical reactions relative to the classical heating reactions were observed.

Keywords

4β-aminopodophyllotoxins anticancer drugs Ritter reaction ultrasound 

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Berger, J. M., Gambin, S. J., Harrison, S. C., & Wang, J. C. (1996). Structure and mechanism of DNA topoisomerase II. Nature, 379, 225–228. DOI: 10.1038/379225a0.CrossRefGoogle Scholar
  2. Bohlin, L., & Rosen, B. (1996). Podophyllotoxin derivatives: drug discovery and development. Drug Discovery Today, 1, 343–351. DOI: 10.1016/1359-6446(96)10028-3.CrossRefGoogle Scholar
  3. Burden, D. A., & Osheroff, N. (1998). Mechanism of action of eukaryotic topoisomerase II and drug targeted to the enzyme. Biochimica et Biophysica Acta — Gene Structure and Expression, 1400, 139–154. DOI: 10.1016/S0167-4781(98)00132-8.CrossRefGoogle Scholar
  4. Canetta, R., Hilgard, P., Florentine, S., Bedogni, P., & Lenaz, L. (1982). Current development of podophyllotoxins. Cancer Chemotherapy and Pharmacology, 7, 93–98. DOI: 10.1007/BF00254528.CrossRefGoogle Scholar
  5. Chen, S. Y., Yu, Y. Q., You, J. Z., & Chen, Y. Z. (2000). Two new methods for synthesis of 4β-amino-4-deoxypodophyllotoxin and 4β-amino-4-demethyl-4-deoxypodophyllotoxin. Chemical Research in Chinese University, 21, 1064–1066.Google Scholar
  6. Cho, S. J., Kashiwada, Y., Bastow, K. F., Cheng, Y. C., & Lee, K. H. (1996a). Antitumor agents. 164. Podophenazine, 2″,3″-dichloropodophenazine, benzopodophenazine, and their 4β-p-nitroaniline derivatives as novel DNA topoisomerase II inhibitors. Journal of Medicinal Chemistry, 39, 1396–1402. DOI: 10.1021/jm950548u.CrossRefGoogle Scholar
  7. Cho, S. J., Tropsha, A., Suffness, M., Cheng, Y. C., & Lee, K. H. (1996b). Antitumor agents. 163. Three-dimensional quantitative structure-activity relationship study of 4′-Odemethylepipodophyllotoxin analogs using the modified CoMFA/q2-GRS approach. Journal of Medicinal Chemistry, 39, 1383–1395. DOI: 10.1021/jm9503052.CrossRefGoogle Scholar
  8. Gordaliza, M., García, P. A., Miguel del Corral, J. M., Castro, M. A., & Gómez-Zurita, M. A. (2004). Podophyllotoxin: distribution, sources, applications and new cytotoxic derivatives. Toxicon, 44, 441–459. document DOI: 10.1016/j.toxicon.2004.05.008.CrossRefGoogle Scholar
  9. Hande, K. R. (1998). Etoposide: four decades of development of a topoisomerase II inhibitor. European Journal of Cancer, 34, 1514–1521. DOI: 10.1016/S0959-8049(98)00228-7.CrossRefGoogle Scholar
  10. Hansen, H. F., Jensen, R. B., Willumsen, A. M., Nørskov-Lauritsen, N., Ebbesen, P., Nielsen, P. E., & Buchardt, O. (1993). New compounds related to podophyllotoxin and congeners: synthesis, structure elucidation and biological testing. Acta Chemica Scandinavica, 47, 1190–1200. DOI: 10.3891/acta.chem.scand.47-1190.CrossRefGoogle Scholar
  11. Kamal, A., Gayatri, N. L., & Rao, N. V. (1998). Facile and improved synthesis of 4β-aminopodophyllotoxin congeners. Bioorganic & Medicinal Chemistry Letters, 8, 3097–3100. DOI: 10.1016/S0960-894X(98)00570-8.CrossRefGoogle Scholar
  12. Kamal, A., Gayatri, N. L., Reddy, D. R., Reddy, P. S. M., Arifuddin, M., Dastidar, S. G., Kondapi, A. K., & Rajkumar, M. (2005). Synthesis and biological evaluation of new 4β-anilino and 4β-imido-substituted podophyllotoxin congeners. Bioorganic & Medicinal Chemistry, 13, 6218–6225. DOI: 10.1016/j.bmc.2005.06.032.CrossRefGoogle Scholar
  13. Kamal, A., Kumar, B. A., Arifuddin, M., & Dastidar, S. G. (2003). Synthesis of 4β-amido and 4β-sulphonamido analogues of podophyllotoxin as potential antitumour agents. Bioorganic & Medicinal Chemistry, 11, 5135–5142. DOI: 10.1016/j.bmc.2003.08.019.CrossRefGoogle Scholar
  14. Kamal, A., Laxminarayana, B., & Gayatri, N. L. (1997). Stereo and chemoselective enzymatic reduction of azido functionality: Synthesis of 4β-aminopodophyllotoxin congeners by Baker’s yeast. Tetrahedron Letters, 38, 6871–6874. DOI: 10.1016/S0040-4039(97)01582-7.CrossRefGoogle Scholar
  15. Keller-Juslen, C., Kuhn, M., Von Wartburg, A., & Staehelin, H. (1971). Mitosis-inhibiting natural products. 24. Synthesis and antimitotic activity of glycosidic lignan derivatives related to podophyllotoxin. Journal of Medicinal Chemistry, 14, 936–940. DOI: 10.1021/jm00292a012.CrossRefGoogle Scholar
  16. Li, G. Z., Feng, R. H., Chen, L. B., Feng, J. T., Tian, X., & Zhang, X. (2006). Synthesis and antifeedant activity of 4β-halogenated-4-deoxypodophyllotoxin and 4β-amino-4-deoxypodophyllotoxin. Chinese Journal of Pesticide Science, 8, 87–90.CrossRefGoogle Scholar
  17. Liu, Y. Q., Yang, L., & Tian, X. (2007). Podophyllotoxin: Current perspectives. Current Bioactive Compounds, 3, 37–66. DOI: 10.2174/157340707780126499.CrossRefGoogle Scholar
  18. Roulland, E., Magiatis, P., Arimondo, P., Bertounesque, E., & Monneret, C. (2002). Hemi-synthesis and biological activity of new analogues of podophyllotoxin. Bioorganic & Medicinal Chemistry, 10, 3463–3471. DOI: 10.1016/S0968-0896(02)00255-9.CrossRefGoogle Scholar
  19. Tian, X., Wang, Y. G., Yang, M. G., & Chen, Y. Z. (1997). Synthesis and antitumor activity of spin labeled derivatives of podophyllotoxin. Life Sciences, 60, 511–517. DOI: 10.1016/S0024-3205(96)00689-3.CrossRefGoogle Scholar
  20. Wang, Z. Q., Kuo, Y. H., Schnur, D., Bowen, J. P., Liu, S. Y., Han, F. S., Chang, J. Y., Cheng, Y. C., & Lee, K. H. (1990). Antitumor agents. 113. New 4β-arylamino derivatives of 4′-O-demethylepipodophyllotoxin and related compounds as potent inhibitors of human DNA topoisomerase II. Journal of Medicinal Chemistry, 33, 2660–2666. DOI: 10.1021/jm00171a050.CrossRefGoogle Scholar
  21. Wilstermann, A. M., Bender, R. P., Godfrey, M., Choi, S., Anklin, C., Berkowitz, D. B., Osheroff, N., & Graves, D. E. (2007). Topoisomerase II-drug interaction domains: Identification of substituents on etoposide that interact with the enzyme. Biochemistry, 46, 8217–8225. DOI: 10.1021/bi700272u.CrossRefGoogle Scholar
  22. Xu, H., Zhang, L., & Tian, X. (2008). A highly improved synthesis of 4β-aminopodophyllotoxin. Chinese Journal of Organic Chemistry, 28, 1243–1246.Google Scholar
  23. Yu, Y. P., Chen, S. Y., Wang, Y. G., & Chen, Y. Z. (1999). A facile and efficient synthesis of 4β-aminopodophyllotoxins. Tetrahedron Letters, 40, 1967–1970. DOI: 10.1016/S0040-4039(99)00125-2.CrossRefGoogle Scholar

Copyright information

© Institute of Chemistry, Slovak Academy of Sciences 2010

Authors and Affiliations

  • Ying-Qian Liu
    • 1
    • 2
  • Lin-Hai Li
    • 2
  • Liu Yang
    • 3
  • Hong-Yu Li
    • 1
    • 2
    Email author
  1. 1.MOE Key Laboratory of Arid and Grassland EcologySchool of Life SciencesLanzhouChina
  2. 2.School of PharmacyLanzhou UniversityLanzhouChina
  3. 3.Environmental and Municipal Engineering SchoolLanzhou Jiaotong UniversityLanzhouChina

Personalised recommendations