Sociedade Brasileira de Espectrometria de Massas – BrMASS
Produtos Naturais e Sintéticos
Synthesis and ESI(+)-MS/MS Study of N-alkyl-lactamic
Aromatic Aminoesters
Renato Sonchini Gonçalves1, Patrícia Verardi Abdelnur2, Rosineide C. Simas2
Marcos N. Eberlin2, Eduardo R. Pérez González1
eperez@fct.unesp.br
Departamento de Física, Química e Biologia, Faculdade de Ciencias e
Tecnologia, UNESP, C.P. 467, Presidente Prudente, 19060-900, SP, Brasil.
2
ThoMSon Mass Spectrometry Laboratory, Institute of Chemistry, State
University of Campinas, Campinas, São Paulo, Brazil.
1
Compounds structurally related to p-aminobenzoic acid (PABA) have shown interesting
pharmacological properties. PABA derivatives such as procaine, benzocaine and
lidocaine are known as local anesthetic. [1] In this work we synthesized benzocaine
like-compounds 1-4 by a nucleophilic aromatic substitution reaction (SNAr) of 4-chloro3-nitrobenzoic acid with N-(3-aminopropyl)-2-azepanone (APA) and N-(3-aminopropyl)2-pyrrolidone (APP) subsequently by coupled with acid catalyzed esterification using
several aminoalcohols. Molecules containing the APA moiety have been reported as
inhibitors of the human tryptase, an important mediator in the asthma pathology, while
APP derivatives were found to be active against H2N2 and H3N2 strains of influenza
virus. On the other hand, APP containing compounds have also been reported as HIV-1
protease inhibitors. [2] All the synthesized products have been characterized by NMR,
FT-IR and Mass Spectrometry. It was realized a more detailed MS study of the
products involving experiments using ESI-MS with high resolution mass to verify if the
generated products had been the proposed chemical formula. To prove the structure of
compounds here described we have performed MS/MS experiments using Argon as
collision gas and the fragmentations confirmed the proposed structures. With these
results, the products had been characterized and their structures were proving by
ESI(+)-MS and ESI(+)-MS/MS.
R
O
C
O
N R
yield 56-70 %
NO2
n( )
N
NH
1. n = 1, R = Me
2. n = 3, R = Me
3. n = 1, R = Et
4. n = 3, R = Et
O
Figure. Synthesis of benzocaine analogues derivative by SNAr – Fisher esterification
coupled reactions.
Reference
[1] Bhananker, S.M.; Azavedo, L.F.; Splinter, W.M. Pediat. Anesthes. 2008, 18, 140-144.
[2] Ghosh, A.K., Leshchenko-Yashchuk, S., Anderson, D.D., Baldridge, A., Noetzel, M., Miller,
H.B., Tie, Y., Wang, Yuan-Fang, Koh, Y., Weber, I.T., Mitsuya|, H. J. Med. Chem. 2009, 52,
3902–3914.
3º Congresso BrMass – 12 a 15 de Dezembro de 2009