Novas dietoxifosfonil-N-acilarilidrazonas e dialquilfosforilidrazonas com potencial atividade biológica

Abstract

Two series of different organophosphorus compounds were synthesized in this work. The first one deals with 6 new diethoxiphosphonyl-N-acylarylhydrazones (2a-f) that were obtained through 3 reaction steps. The first step takes place through a Michaelis-Arbuzov reaction where the triethyl phosphite reacts with bromine ethyl acetate, giving the triethyl phosphono acetate with a 95% yield. The second step, involves reaction of triethyl phosphonacetate with monohydrated hidrazine to give a phosphonacyl hydrazine, through an acid-catalyzed condensation. The phosphonacyl hydrazine obtained then reacts with different substituted aromatic aldehydes to give the respective products (2a-2e) except in the case of compound 2f where in the last step it reacts with b-lapachone. The analysis of the 1H NMR spectra allowed to observe a mixture of the two possible diastereomers (E/Z) for the first five compounds (2a-2e). The second series with 13 new dialkylphosphorylhydrazones (4a-e and 6a-h) was synthesized, also in three reaction steps. The first one consists of the synthesis of different dialkyl phosphites which are obtained through the reaction of phosphorus tricloride (PCl3) with three mols of the corresponding alcohol. In the second step, the reaction of the dialkyl phosphites with hydrazine, in a two-phase system, gives the respective dialkylphosphorylhydrazines. The last step is the condensation reaction of these dialkylphosphorylhydranines with different substituted aromatic aldehydes. The analysis of the 1H NMR spectra allowed to observe a single stereoisomer with probable E stereochemistry. All the compounds were characterized by 1H, 13C and 31P NMR, IR and mass spectroscopy. Eight of the synthesized compounds (4a, 4b, 6a, 6b, 6d, 6e, 6f,e 6g) were evaluated against Artemia salina Leach showing low toxicity, five of them (4e, 6b, 6d, 6e and 6g) were evaluated for their ability to inhibit germination of tomato seeds and compound 4e was found to be very active. Six of the compounds (2b, 2c, 2d, 2e, 6b and 6d) were evaluated for their potential in inhibiting proliferation of two protozoa (Giardia lamblia and Leishmania amazonensis), and in both cases, compound 6b showed the strongest activity.