Synthesis of Analogue to Camptothecine

Authors: Abdulkareem Hamid, Adam Daïch

Abstract:

Camptothecin (CPT) is a cytotoxic quinoline alkaloid, which inhibits the DNA enzyme topoisomerase I (topo I). It was discovered in 1966 by M. E. Wall and M. C. Wani in systematic screening of natural products for anticancer drugs. It was isolated from the bark and stem of Camptotheca acuminata (Camptotheca, Happy tree), a tree native in China. CPT showed remarkable anticancer activity in preliminary clinical trials but also low solubility and (high) adverse drug reaction. Because of these disadvantages synthetic and medicinal chemists have developed numerous syntheses of Camptothecine [1][2][3] and various derivatives to increase the benefits of the chemical, with good results. In our method CPT analogues has be six steps starting from available material DL Malic acid.

Keywords: Camptothecine, synthesis, analogue.

Digital Object Identifier (DOI): doi.org/10.5281/zenodo.1084622

References:

[1] Lee, Y. S.; Kang, D. W.; Lee, S. J.; Park, H. Synth. Commun. 1995, 25, 1947. (b) Lee, Y. S.; Kang, D. W.; Lee, S. J.; Park, H. J. Org. Chem. 1995, 60, 7149. (c) Lee, J. Y.; Lee, Y. S.; Chung, B. Y.; Park, H. Tetrahedron 1997, 53, 2449. (d) Lee, Y. S.; Kang, S. S.; Choi, J. H.; Park, H. Tetrahedron 1997, 53, 3045.
[2] Louwrier, S.; Ostendorf, M.; Boom, A.; Hiemstra, H.; Speckamp, W. N. Tetrahedron 1996, 52, 2603.
[3] Polniaszek, R. P.; Belmont, S. E. J. Org. Chem. 1991, 56, 4868 et les références citées.
[4] Chihab-Eddine, A.; Daïch, A.; Jilale, A.; Decroix, B. Tetrahedron Lett. 2001, 42, 573
[5] Marson, C. M.; Pink, J. H.; Hall, D.; Hursthouse, M. B.; Malik, A.; Smith, C. J. Org. Chem. 2003, 68, 792
[6] Lee, L. S.; Yan, J-.L.; Wang, K. C. Tetrahedron: Asymmetry 1997, 8, 3051.
[7] (a) Cheng, C.-C.; Yan, S.-J. In Organic Reactions; Dauben, W. G., Ed.; John Wiley & Sons: New York, 1982; Vol. 28, Chapitre 2. (b) Friedländer, P. Berichte 1882, 15, 2572. (c) Jones, G. In Comprehensive Heterocyclic Chemistry II; Ramsden, C. A., Ed.; Pergamon Press: Tarrytown, 1996; Vol. 5., Chapitre 5. (d) Lowe, P. A. In Comprehensive Heterocyclic Chemistry; Boulton, A. J., McKillop, A., Eds.; Pergamon Press: New York, 1984; Vol. 2, Chapitre 2.11
[8] (a) Yadav, J. S.; Reddy, B. V. S.; Premalatha, K. Synlett 2004, 963. (b) Wu, J.; Zhang, L.; Diao, T.-N. Synlett 2005, 2648. (c) De, S. K.; Gibbs, R. A. Tetrahedron Lett. 2005, 46, 1647. (d) Wang, G-.W.; Jia, C-.S.; Dong, Y-.W. Tetrahedron Lett. 2006, 47, 1059
[9] Borsche, W.; Ried, W. Justus Liebigs Ann. Chem. 1943, 554, 269
[10] McNaughton, R. B.; Miller, L. Org. Lett. 2003, 5, 4257.