Estudos para a síntese da viscosamina, de análogos oxigenados e de novos sais de piridínio quirais usando a reação de zincke

Abstract

This work was divided into two parts. The first part deals with the attempt at the synthesis of the marine alkaloid viscosamine, a macrocycle of natural occurrence, and its oxygenated analogues. The second part deals with the synthesis of chiral pyridinium salts. The Zincke's reaction was chosen to perform the key step that would lead to viscosamine and its oxygenated analogues; and for the introduction of the stereocenter directly linked to the ring nitrogen of chiral pyridinium salts. The studies to obtain viscosamine did not lead to total synthesis of this alkaloid. In addition to the several difficulties encountered during the attempts to obtain this compound, its synthesis was described for the first time by another group during our research work. So it was decided to interrupt the viscosamine synthesis, and start the synthesis of new oxygenated analogues of this alkaloid. In this work a new oxygenated macrocycle was obtained in low yield. During our attempts of the synthesis of viscosamine analogues we obtained a new oxygenated analogue of marine alkaloid teonalidine C. For the synthesis of chiral pyridinium salts, new compounds with different chain alkyl groups attached to position 3 of the pyridine ring were obtained. It was also shown that is possible to use microwaves for the synthesis of Zincke's salts in the absence of any solvent, and for the synthesis of several chiral pyridinum salts using 1-butanol or water as a solvent of the reaction. The use of microwaves irradiation to prepare compounds in the absence of solvent or the synthesis of molecules in water as described above, is very important regarding the development of safer and ecologically correct methodologies. Finally, for the first time the antimicrobial activity of Zincke's salts was quantified. Of the eleven salts tested at least nine of them showed activity against one of the bacteria tested.