Withanolides from Jaborosa reflexa

GARCÍA, M. E.; NICOTRA, V. E; BURTON, G.; OBERTI, J.C

Venecia, Italia

Otro; 10th Summer School on Green Chemistry.; 2008

INCA

Withanolides from Jaborosa reflexa   Manuela E. García,a Viviana E. Nicotra,a Gerardo Burton,b and Juan Carlos Obertia   a Depto. de Química Orgánica, Facultad de Ciencias Químicas (IMBIV-CONICET), Universidad Nacional de Córdoba, Córdoba (CP5000), b Depto. de Química Orgánica, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Ciudad de Buenos Aires (CP1428).   Natural products play a highly significant role in the drug discovery and development process. This was particularly evident in the areas of cancer and infectious diseases, where over 60% and 75% of these drugs, respectively, were shown to be of natural origin.[1] Withanolides are a group of oxygenated steroidal lactones isolated from several genera of the plant family Solanaceae. Jaborosa Miers is a South American genus belonging to the Solanaceae that comprises about 23 different species that grow mainly in Argentina.[2] Many of them exhibit a variety of biological activities such as inducers of the enzyme quinone reductase, [3] insecticidal[4] and phytotoxic activity,[5] among others. As part of our investigations of the withanolides of Jaborosa Miers species, we studied the withanolides from Jaborosa reflexa. The aerial parts of J. reflexa were air dried and extracted with ethanol. After concentration and defatting, the residue was fractionated by a combination of chromatographic techniques, ultimately affording three new withanolides (I-III). The withanolides I and II have a hemiketal ring formed between a 21-hydroxyl and a 12-ketone. The compound III, a 12-oxowithanolide, may function as a biosynthetic precursor to I and II.[6] The full and unambiguous proton and carbon NMR assignments for compounds I-III were performed using a combination of, DEPT, COSY-60, HSQC y HMBC experiments.     As part of a project aimed at the search of withanolides with potential application as friendly environmentally herbicides, we report the phytotoxic activity of the main compound from J. reflexa, (I), related structurally to Jaborosalactona 38 isolated from J. caulescens.[7] Compound I was tested on seed germination and radicle length on both a dicotyledon (Lactuca sativa) and a monocotyledon (Avena sativa) as standard target species in the range concentration 15-400 ppm. This metabolite produce a significant inhibition of radicle growth at 150 ppm on Lactuca sativa (41 %), while on Avena sativa the corresponding inhibition was quite small (6%). Dependency of the inhibiting activity with the concentration is not observed. Similar selective inhibition effect on dicotyledon species was reported for Jaborosalactona 38.   [1]           Newman, D. J.; Cragg, G. M.; Snader, K. M., J. Nat. Prod., 2003, 66, 1022-1037. [2]           Hunziker, A. T. The Genera of Solanaceae Illustrated: Arranged According to a New System; A. R.     G. Gantner Verlag K.-G.; Ruggell, Germany, 2001, xvi, 500 pp. [3]           Kenelly, E. J.; Gerhauser, C.; Song, L. L.; Graham, J. G.; Beecher, C. W. W.; Pezzuto, J. M.;   Kinghorn, A. D. J. Agric. Food Chem. 1997, 45, 3771-3777. [4]           Veleiro, A. S.; Oberti, J. C.; Burton, G. in Bioactive Natural Products (Part M), Ed. Atta-ur   Rahman. Series Studies in Natural Products Chemistry, Vol. 32, Elsevier Science Publishers, Amsterdam, 2005.pp. 1019-1052. [5]           Vaccarini, C. E.; Bonetto, G. M.; J. Chem. Ecol. 2000, 26, 2187-2193. [6]           Ramacciotti, N. S.; Nicotra, V. E.; J. Nat. Prod., 2007, 70, 1513-1515. [7]           Nicotra, V.E.; Gil, R.R.; Oberti, J.C.; Burton G., J. of Nat. Prod. 2007, 70, 808-812.