DOI QR코드

DOI QR Code

Analytical Characterization of Aza-Indole Alkaloids in the Biosynthesis of Catharanthus Roseus

  • Lee, Hyang-Yeol (Department of Biotechnology, Korea National University of Transportation)
  • Received : 2012.05.23
  • Accepted : 2012.06.21
  • Published : 2012.06.30

Abstract

Aza-indoles are important pharmacophores that have similar size and biological properties of indole. Here we have synthesized 4- and 7-azaindole tryptamines and showed that they are successfully incorporated in the biosynthesis of monoterepene indole alkaloids (MIAs) to form novel azaindole alkaloids by enzymatic reactions of strictosidine synthase(STR) and strictosidine glucosidase(SDG) monitored by UPLC/MS. By using HPLC equipped with a HPLC photo diode array(PDA) detector, each of the UV spectra of azaindole alkaloids was obtained and characterized. When hydrophilicity of azaindole alkaloids was compared, 4-azaindole alkaloids were more hydrophilic than 7-azaindole alkaloids.

Keywords

References

  1. T. K. Alder, and A. Albert, The Biological and Physical Properties of The Azaindoles. J. Med. Chem., 6, 480 (1963). https://doi.org/10.1021/jm00341a003
  2. M. Pullagurla, M. Dukat, B. L. Roth, V. Setola and R.A. Glennon, 5-Azatryptamine Analogures as H5-HT6 Serotonin Receptor Ligands. Med. Chem. Res. 14, 1 (2005). https://doi.org/10.1007/s00044-004-0121-8
  3. S. Lee and H.-Y. Lee, Studies of Vindoline Metabolism in Catharanthus Roseus Cell Cultures using Deuteriumlabeled Tabersonine. J. of Korean Oil Chemists' Soc., 29(1), 71 (2012).
  4. H.Y. Lee, N. Yerkes, and S. E. O'Connor, Aza-tryptamine Substrates in Monoterepene Indole Alkaloid Biosynthesis. Chemistry & Biology, 16, 1225 (2009). https://doi.org/10.1016/j.chembiol.2009.11.016
  5. C. Marminon, A. Pierre, B. Pfeiffer, V. Perez, S. Leonce, A. Joubert, C. Bailly, P. Renard, J. Hickman and M. Prudhomme, Synthesis and Antiproliferative Activities of 7-azarebeccamycin Analogues Bearing one 7-azaindole Moiety, J. Med. Chem. 46, 609 (2003). https://doi.org/10.1021/jm0210055
  6. R. W. Schumacher and B. S. Davidson, Didemnolines a-d, new N9-substituted Beta-carbolines from The Marine Ascidian Didemnum sp. Tetrahedron 51, 10125 (1995). https://doi.org/10.1016/0040-4020(95)00594-X
  7. J.J. Maresh, L. A. Giddings, A. Friedrich, E.A. Loris, S. Panjikar, B.L, Trout, J. Stockigt, B. Peters and S.E. O'Connor. Strictosidine Synthase: Mechanism of a Pictet-Spengler Catalyzing Enzyme. J. Am. Chem. Soc., 130, 710 (2008). https://doi.org/10.1021/ja077190z
  8. E. McCoy, M. C. Galan and S. E. O'Connor, Substrates Specificity of Strictosidine Synthase, Bioorg. Med. Chem. Lett., 16, 2475 (2006). https://doi.org/10.1016/j.bmcl.2006.01.098
  9. A. Klapars and S. L. Buchwald, Copper-catalyzed Halogen Exchange in Aryl Halides: An Aromatic Finkelstein Reaction. J. Am. Chem. Soc., 124, 14844 (2002) https://doi.org/10.1021/ja028865v
  10. J. Y. Merour, and B. Joseph, Synthesis and Reactivity of 7-azaindoles (1H-pyrrol[2,3-b]pyridine), Curr. Org. Chem. 5, 471 (2001).
  11. F. Ujjainwalla and D. Warner, Synthesis of 5-, 6- and 7-azaindoles Via Palladium-catalyzed Heteroannulation of Internal Alkynes. Tetrahederon Lett., 39, 5355 (1998). https://doi.org/10.1016/S0040-4039(98)01069-7
  12. Z. Zhang, Z. Yang, H. Wong, J. Zhu, N.A. Meanwell, J.F. Kadow, and T. Wang, An Effective Procedure for The Acylation of Azaindoles at C-3. J. Org. Chem., 67, 6226 (2002). https://doi.org/10.1021/jo020135i
  13. P. Bernhardt, E. McCoy and S. E. O'Connor, Rapid identification of Enzyme Variants for Reengineered Alkaloid Biosynthesis in Periwinkle, Chem. Biol., 14, 888 (2007). https://doi.org/10.1016/j.chembiol.2007.07.008
  14. Y. Yamazaki, A. Urano, H. Sudo, M. Kitajima, H. Takayama, M. Yamazaki, N. Aimi, K. Saito, Metabolite Profiling of Alkaloids and Strictosidine Synthase Activity in Camptothecin Producing Plants, Phytochemistry, 62, 461 (2002).
  15. P. Bernhardt, N. Yerkes, and S. E. O'Connor, Bypassing Stereoselectivity in The Early Steps of Alkaloid Biosynthesis, Org Biomol Chem., 7 (20), 4166 (2009). https://doi.org/10.1039/b916027m
  16. S. Hisiger and M. Jolicoeur, Analysis of Catharanthus Roseus Alkaloids by HPLC, Phytochem Rev., 6, 207 (2007). https://doi.org/10.1007/s11101-006-9036-y
  17. P. J. Facchini, Alkaloid Biosynthesis in Plants: Biochemistry, Cell Biology, Molecualr Regulation, and Metabolic Engineering Applications, Annu. Rev. Plant Physiol. Plant Mol. 52, 29 (2001). https://doi.org/10.1146/annurev.arplant.52.1.29