Bioactive triterpenoids of the Rutales.

This thesis describes the investigation of the bioactivity of triterpenoids, limonoids and spiro-triterpenoids, isolated from the order of the Rutales. The focus of this research has been towards the development of botanical insecticides with non-neurotoxic modes of action in insects. It follows the recent development of Neem (Azadirachta indica, Meliaceae) as a botanical insecticide containing a limonoid azadirachtin as its main active compound. Because so few Meliaceae members have been examined for insecticidal activity the project was initiated by the screening of over sixty ethanol extracts of various parts of twenty species (collected from Costa Rica and the Tropical Museum in Miami, Florida) for bioactivity against the European corn borer (Ostrinia nubilalis) and the Variegated cutworm (Peridroma saucia). The data suggest that a majority of the extracts studied inhibited growth significantly; some are more active than neem leaf extracts. Swietenia mahogani bark, Trichilia glabra bark, T. hirta leaves, T. americana bark, T. trifolia wood, T. pleana and Azadirachta indica wood showed potent activity against the cutworm. Ruptiliocarpon caracolito bark, Cedrela odorata leaves, Aphanamixis polystachys wood, T. glabra wood and T. pleana bark showed good activity against the corn borer larvae. Bioassay guided fractionation of the most active crude extract, the bark of Ruptiliocarpon caracolito, has resulted in the isolation of six very novel spiro-CD-triterpenoids, the spirocaracolitones. The spirocaracolitones, at 100 ppm, were screened for antifungal activity against Fusarium using a hyphal growth bioassay. After 48 h a high degree of inhibition of growth (59-79%) was observed. These novel triterpenoids exhibited no antimalarial activity when screened against Plasmodium falciparum. A study of the effects of these compounds, incorporated into artificial diet, on the neonate life cycle of the European corn borer was conducted. All the spirocaracolitones effected the growth and the development of the insects but spirocaracolitone B and spirocaracolitone C were substancially more active than the other spirocaracolitones. Two postulates dealing with the biosynthesis of these unique spiro-compounds are also presented. Both commence with a friedelin derivative because canophyllol was isolated in large quantities from the hexane extract. They envisage generation of a carbocation at C12 followed by migration of the C23 methyl group this results in the formation of a carbocation at C13. The spirosystem results from migration of the C8-C14 bond. An investigation of the structure/activity relationships of gedunin was conducted to determine the moieties responsible for its antimalarial and/or antifeedant properties. Ten derivatives of gedunin were prepared (1,2-dihydrogedunin, 1,2-epoxygedunin, 1,2-dihydro-3$\beta$-gedunol, 3$\beta$-acetoxy-1,2-dihydrogedunin, 7-deacetylgedunin, 7-ketogdunin, hexahydrogedunin, tetrahydrogedunin, 21-acetylgedunin, 23-acetylgedunin) along with five other limonoids (limonin, epilimonol, nomilin, obacunone, hirtin) closely related to gedunin were evaluated for antifeedant activity (Ostrinia nubilalis) and antimalarial activity (Plasmodium falciparum). Evaluation of these compounds for antimalarial activity presented no increase in activity however it was clearly determined that alterations to the enone in ring A and at C7 of gedunin resulted in large losses of activity. Evaluation of the effects of these limonoids on the neonate life cycle of the European corn borer at 5 and 50 ppm incorporation into the artificial diet did lot produced dramatic effects on the growth and development of the larvae. At these concentrations structure/activity relationships could not be proposed.$\sp*$ ftn$\sp*$Please refer to the dissertation for diagrams