YAKHAK HOEJI (약학회지)

The Pharmaceutical Society of Korea (대한약학회)
권호 표지

Modified Synthetic Method & Cytotoxic Activity of Ranunculin and Protoanemonin

Ranunculin및 Protoanemonin의 합성법의 개선 및 세포독성 평가

  • 방성철 (충남대학교 약학대학) ;
  • 김용 (충남대학교 약학대학) ;
  • 안병준 (충남대학교 약학대학)
  • Published : 2004.04.01
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Abstract

Ranunculin, a potent cytotoxic component of P. koreana, was synthesized by reacting (s)-(-)-5-(hydroxymethyl)-2(5H)-furanone with 2,3,4,6-tetra-O-acetyl-$\alpha$-D-glucopyranosyl bromide and successive removal of the acetyl protecting group by 0.5 M HCl/MeOH. A new deacetylation process of the intermediate tetraacetylranunculin was deviced giving a yield of 83% of ranunculin. Protoanemonin, the cytotoxic structural moiety of ranunculin, was synthesized by dehydration of (s)-(-)-5-hydroxymethyl-2(5H)-furanone. Ranunculin showed a moderate cytototoxic activity against A-549 (ED$_{50}$=7.53 $\mu\textrm{g}$/$m\ell$), NIH3T (ED$_{50}$=13.6$\mu\textrm{g}$/$m\ell$), and SK-OV-3 (ED$_{50}$=17.5 $\mu\textrm{g}$/$m\ell$). Meanwhile, protoanemonin also exhibited moderate cytotoxicity against A-549 (ED$_{50}$=9.38 $\mu\textrm{g}$/$m\ell$), NIH3T (ED$_{50}$=13.8 $\mu\textrm{g}$/$m\ell$), and SK-OV-3 (ED$_{50}$=15.1 $\mu\textrm{g}$/$m\ell$). It was found that both of the synthetic products showed a potenter cytotoxicity against A-549.ainst A-549.

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References

  1. Bae, K. H. : The medicinal plants of korea (1999)
  2. Wen, C. Y., Nine, N. J., Shou, X. Z., Jing, H. L., Mckervey, M. A. and Stevenson, P. : Triterpenoids from Pulsatilla chinensis, Phytochemistry. 42(3), 799 (1996)
  3. Kim, Y. : Medicinal chemical study on a preparation comprising of pulsatilla koreana, panax ginseng, glycyrrhizae glabra (2001)
  4. Camps, P., Cardellach, J., Font, J., Ortuno, R. M. and Ponsati, O. : Studies on structurally simple $\alpha}$,$\beta$-butenolides-II. Tetrahedron 38, 15, 2395 (1982).
  5. Martin, M. L. and San, R. L. : Dominguez, A. In vitro activity of protoanemonin, an antifungal agent. Planta Med. 56, 66 (1990)
  6. Campbell, W. E., Cragg, G., M. L. and Powrie, A. H. : Anemonin, protoanemonin and ranunculin form Knowltonia capensis. Phytochemistry 18, 323 (1979) https://doi.org/10.1016/0031-9422(79)80083-7
  7. Li, R. Z. and Ji, X. J. : The cytotoxicity and action mechanism of Ranunculin in vitro, Yao Hsueh Hsueh Pao. 28(5), 326 (1993)
  8. Alibes, R., Josep, F., Mula, A. and Ortuno, R. M. : Studies on structurally simple $\alpha$,$\beta$-butenolides. Synthetic Communications 20(17), 2607 (1990). https://doi.org/10.1080/00397919008051468
  9. Skehan, P., Storeng, R., Scudiero, D., Monks, A., McMahon, J., Vistica, D., Warren, J. T., Bokesch, H., Kenney, S. and Boyd, M. R. : New colorimetric cytotoxicity assay for anticancer-drug screening. J. Natl. Cancer Inst. 82, 1107 (1990) https://doi.org/10.1093/jnci/82.13.1107
  10. Brian, S. F, Antony, J. H., Peter, W. G. S. and Austin, R. T. : Vogel's Textbook of practical organic chemistry, 5th edition (1989)
  11. Bradford, P. M. and Michael, G. E. : Name Reactions and Reactions in Organic Synthesis in Wiley press, 3th edition, 126 (1999)
  12. Peter Collins. Robin Ferrier: Monosaccharides in Wiley press , 5 (1995)
  13. Jozef, A. J. M. V., Gabriel, A. M. F., Gordon, J. F. C. and Erik, F. G. : An efficient synthesis of (S)-5-hydroxymethyl-2(5H)Furanone, Tetrahedron Letters 28, 20, 2299 (1987)