Derivados de 2H-cromen-2-onas acoplados a L-aminoácidos via reação de Ullmann empregados na síntese de 1,3,4-oxadiazóis 2,5-dissubstituídos

Abstract

In the following work, an unprecedented series of 2,5- disubstituted 1,3,4- oxadiazole 3 was synthesized from 2H-chromen-2-ones-L-amino acids derivatives 1, targeting the union of 2H-chromen-2-one, L-amino acid and 1,3,4-oxadiazole pharmacophoric centers. The synthesis of 2H-chromen-2-ones-L-amino acids derivatives 1a-d was performed by Ullmann coupling reaction between 6-halogen- 2H-chromen-2-one and an L-amino acid, providing a novel of products in yields of 44-78%. The amino acids used in this synthesis were L-valine, L-isoleucine, Lphenylalanine and L-methionine, leading to products 1a, 1b, 1c and 1d, respectively, where compound 1a showed antifungal activity. The 2,5-disubstituted 1,3,4- oxadiazole 3 were obtained from the reaction between 2H-chromen-2-ones-L-amino acids derivatives 1a-d and benzoyl hydrazides 2a-d (a = benzohydrazide, b = 4- tolyl-hydrazide, c = 4-methoxy- benzohydrazide, d = 4-bromo-benzohydrazide), with yields of 16-72 %. All 1,3,4-oxadiazoles showed fluorescence activity and compounds 3aa, 3ab and 3ac showed antibacterial activity.