Studies on the chemistry of Phalaris canariensis and other natural products

The thesis is presented in two parts with one appendix. Part I was prompted by a report that the starch isolated from the seeds of Phalaris Canariensis possessed hypotensive activity. A review of the literature on Phalaris species is presented and the isolation of the starch and its extracts is described. No hypotansive activity of the starch or its extracts was found. Chemical examination of aqueous extracts of the starch showed the presence of choline, glucose, maltose, azelaic acid and aminoacids. Ion exchange and paper chromatography were used to identify serine, alpha-alanine, phenylalanine, leucine, proline, aspartic acid, valine and aminobutyric acid. The light petroleum soluble matter of the powdered seeds was examined and a mixture of sterols was isolated. beta-sitosterol was identified in the mixture by conversion of the sterols to the methyl ethers and examination of the ethers by gas chromatography; two other components in the mixture were not identified. It is also shown that the "beta-sitosterol" isolated from Aristolochia reticulata consisted of two components one of which is - sitosterol. The fatty acids in the extract were identified as myristic, palmitic, stearic, oleic and linoleic acids, and glycerol was also isolated. Part II has as its main theme the attempted synthesis of aristolochic acid. A review of the degradation work carried out on aristolochic acids is given followed by an account of the pharmacological activity of extracts and compounds isolated from Aristolochia species. After a report on the synthesis of derivatives of aristolochic acid, in which the benzoate of 8-methoxy-3,4-methylendioxy-10-nitro-l-phenanthroic lactam was obtained as the only new product, a route to aristolochic acid is proposed. This was based on the Pschorr Synthesis, as one of the required intermediates, 2-nitro-methoxybenzaldehyde was known. The attempted preparation of the other intermediate, 6-carboxy-3.4-methylenedioxyphenyl-nitromethane, is discussed and the structure for a new compound obtained during this work is suggested. The lack of success in this stage turned attention to the synthesis of 3.4-methylenedioxyphenylnitromethane and the corresponding 6-bromo-compound and both compounds were obtained by two routes. One of these involved the use of metal nitrites and the conditions used and reactions taking place are considered in some detail. The condensation of the nitro-compound with benzaldehyde and substituted benzaldehydes was investigated and the following compounds were prepared. alpha-nitro-6-bromo-3.4-methylenedioxy-2'-nitro-6'-methoxystilbene. alpha-nitro-3.4-methylenedioxy-2'-nitro-6'-methoxystilbene. alpha-nitro-6-bromo-3.4-methylenedioxy-6'-methoxystilbene alpha-nitro-6-bromo-3.4-methylenedioxy-2'-nitrostilbene. alpha-nitro-3.4-methylenedioxy-2'-nitrostilbene. Side reactions occuring during the condensation are discussed and tentative structures advanced for two of the products. Attempted condensation of acetylaminobenzaldehyde with the substituted phenylnitromethanes met with no success. Selective reduction of alpha-nitro-6-bromo-3.4-methylenedioxy-2'-nitrostilbene and alpha-nitro-3.4-methylenedioxy-2'-nitrostilbene by ammonium sulphide caused the elimination of one nitro-group from each compound and evidence is presented to show that the products were 6-bromo-3.4-methylenedioxy-2'- nitrostilbene and 3.4-methylenedioxy-2'-nitrostilbene respectively. The reduction of the nitro-compounds was also attempted by a variety of reducing agents, but no satisfactory product was isolated. In order to avoid selective reduction of a nitro-group irradiation of alpha-nitro-6-bromo-3.4-methylenedioxy-6'-methoxystilbene and 6-bromo-3.4-methylenedioxy-2'-nitrostilbene was attempted on the micro-scale, but ultraviolet absorption evidence indicated that the phenanthrene nucleus was not formed. Part II concludes with an assessment of the results obtained and a scheme for further work is proposed. The appendix presents the results of an examination % of extracts of small quantities of the roots and rhizomes of goldieana and of the aerial parts of A. indica. No aristolochic acid was isolated from the extracts