Obtenção de derivados do lapachol e de compostos relacionados

Abstract

Lapachol (3) is extracted from ipê-roxo (Tabebuia impetiginosa) wood. Other naphthoquinones are obtained from it, such as and -lapachones (4), (5), and also 2-methoxy-lapachol (6). Lately there has been a great interest in quinone cemistry, mainly due to their biological activity. The objective of the present work was the preparation of compounds derived from these naphthoquinones through reaction with in situ generated organometallics. The quinols (tertiary alcohols) which were obtained were mono-addition products in all cases. The possibility of dehydration of these alcohols was studied, both by heating in acidic media and by the use of the iodine/triphenyl-phosphine system (which was also used in reactions with tertiary alcohols obtained from phenantherenequinone and from 1,2-diphenyl-ethane-dione). Investigated was the reactivity of 3 and 6 towards nucleophilic nitrogen reagents, without or with base (in excess. It was observed that in all cases of reactions with 6 in the absence of base there was addition to the carbonyl at C1 and products with Z stereochemistry, indicated by the characteristic signal at low field in the 1H NMR spectra, due to intramolecular hydrogen bond. Reactions with excess base resulted, in one case, in substitution of the methoxyl, with intermediate formation of α-xyloidone, which then reacted with semicarbazide to generate the carbonyl addition product (at the carbonyl not conjugated with the alkoxy group). In another case, substitution of the methoxyl resulted in replacement by nitrogen and formation of a cyclic product with two ketone carbonyl absorptions in the 13C NMR spectrum. Reactions performed with 3 resulted only in addition to carbonyl (C1), no substitution products being observed. Obtained were the oximes from -lapachone (Z stereochemistry) and from -lapachone, which also had Z stereochemistry in CDCl3 solution but in the solid state, after recrystallization from ethanol, showed E configuration and dimers, united by two intramolecular hydrogen bonds, as determined by analysis of X-ray diffraction spectra – in these cases addition also occurred exclusively at the carbonyl not conjugated with the alkoxy group. The toxicity of the synthetized compounds was evaluated for the Chagas desease and malaria agents, Tripanosoma cruzi and Plasmidium falciparum, respectively, compound 55 was the most active in both cases.