Estudo de tranformações químicas e de Atividades biológicas de um limonóide do tipo A- seco e do Lupeol

Abstract

During the chemical investigation of Lophanthera lactescens Ducke, family Malpighiaceae, a number of compounds were isolated, among them a new limonoid which was named LLD-3 and since this compound is highly functionalized, various transformations were attempted. Two dehydration reactions were attempted using either p-TsOH or DCC but only starting material was recovered. In order to investigate the possible influence of steric effects, a molecular modelling study of the original compound and of its unsaturated derivatives was also made. Hydrogenation of LLD-3 with Pd-C 10% led to the reduction of only the C1- C2 double bond, which was shown by NMR spectroscopy. Farmacological tests were also carried out but did not shown antiinflamatory activity even 0,5 mg/kg doses. LLD-3 in the conditions used in these tests is able to induce toxic effects on the hepatic tissue and also gives rise to lesions in the urinary sistem. A new isolation of LLD-3 from a another sample of wood furnished only an amount too small to be useful for further reactions and as an alternative, a few derivatives of lupeol were prepared and tested against HIV. Hydrogenation of lupeol with Pd-C 10% afforded the saturated compound as proven by NMR and IR spectroscopy. Epoxidation of the double bond of lupeol with m-CPBA led to the expected product, confirmed by NMR and IR spectroscopy. Reaction of the epoxide with LiAIH 4 led to the formation of the corresponding alcohol as shown by NMR and IR spectroscopy. Anti-HIV tests with lupeol-29-ol and lupeoI-EP afforded around 40% inhibition of HIV-1 in MT2 cells (similar to H9 cells). Lupeol and its saturated derivative lupeoI-H were not tested because they were not soluble in the solvent used (DMSO).