Estudos envolvendo a modificação e a interação do lapachol com compostos de metais de transição

AUTOR(ES)
DATA DE PUBLICAÇÃO

2000

RESUMO

This thesis is concerned with some studies of the natural compound 2-hidroxy-3(3-methyl-2-butenyl)-1,4-naphtoquinone, popularly known as lapachol. In Chapter I, a review is presented which includes the descriptions of procedures for the extraction of lapachol, its synthesis, physical, spectroscopic and structural properties, its biological activities, some of its transformations into known natural products and its reactions with amines. The importance of transition metal compounds in cancer chemotherapy is also discussed and the rare examples of transition metal compounds containing the lapacholate ligand are presented. Chapter II is concerned with the development of procedures for the extraction and purification of lapachol, both at bench and pilot plant scales, from yellow ipê wood which probably belongs to the Tabebuia ochracea gender. A 2 factorial experiment with two factors, C and V - concentration and volume of the Na2CO3 solution, respectively - and two levels (+ and -), with a triplicate central point (C0V0) which was used in the optimisation of the extraction process at bench scale (50,0 g of powdered wood), is described. The process was then reproduced at pilot scale with 2 Kg of powdered wood from which lapachol was obtained in approximately 1% yield, after crystallisation from CH2CI2/hexane, at the approximate cost of US$ 1.70/g, considering only reagents and solvents. In Chapter III, the syntheses of some derivatives of lapachol are described. Methylation of lapachol resulted in 2-methoxy-3(3-methyl-2butenyl)-1,4-naphtoquinone, (2), in 60% yield. The novel secondary amines 2N-alyl- and 2N-benzyl-3(3methyl-2butenyl)-1,4naphtoquinones, (3) and (4), respectively, where obtained from the reactions of compound 2 with alyl and benzylamine in 63 and 65% yields, respectively. A novel product, 2-hidroxy-3(3-methyl-butyl)-tetrahydronaphtalene-1,4-dione, (5), was also obtained from the hydrogenation of the quinone ring and the isoprenyl radical of lapachol, using Pd/charcoal as catalyst. Selective hydrogenation of the isoprenyl radical of compound 2 was also achieved in the presence of [lr(h-cod)(py)(tcyp)][PF6], with formation of 2-methoxy-3(3-methyl-butyl)-1,4-naphtoquinone, (6).All compounds where characterised by elemental analyses and H, {H} C NMR spectroscopy. Some reactions of lapachol and its derivatives 3 and 4 with rhodium and iridium organometallic compounds are described in Chapter IV. The reactions of lapachol with trans-[RhCl(CO)(PPh3)2], (7), trans-[IrCl(CO)(PPh3)2], (8) and [Rh2(m-CI2)(CO)4], (9), were studies under a variety of conditions, but no stable product was isolated from the coordination of the lapacholate anion to the metal centres. The reaction of the amine 4 with the dimeric species 9 in MeCN led to the formation of dicarbonylchloro-2N-alyl- 3(3methyl-2butenyl)1,4,naphtoquinonerhodium(I), (10), in low yields, whose identity was established by IR spectroscopy. Chapter V contains the experimental details of this work.

ASSUNTO(S)

quinona hidrogenação aminas naftoquinona rodio

ACESSO AO ARTIGO

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