Synthesis, characterization, absolute structural determination and antifungal activity of a new chlorinated aromatic avenaciolide analogue.
BACKGROUND
Avenaciolide, a natural product isolated from Aspergillus avenaceus H. Smith, possesses several interesting biological properties, such as antifungal and antibacterial activities and inhibition of glutamate transport in mitochondria. In a study aiming to discover new compounds with antifungal activity, a bis-gamma-lactone analogous to avenaciolide was prepared and characterized by elemental analysis, mass spectrometry, and infrared and NMR spectroscopy.


RESULTS
The absolute structures of this compound and of the synthetic precursor (also a bis-gamma-lactone) were determined by X-ray diffraction analysis. The bis-gamma-lactones synthesized crystallize in the orthorhombic space group P2(1)2(1)2(1), and the crystal packings are supported by C--H...O hydrogen bonds. The compound showed antifungal activity against Colletotrichum gloeosporioides (Penz.) Penz. & Sacc., while the synthetic precursor was inactive under the in vitro test conditions employed.


CONCLUSIONS
The results indicate that it is not only the bis-gamma-lactone skeleton that is important to antifungal activity. The latter also depends on the presence of the exocyclic double bond possibly due to a Michael addition type reaction with the fungal enzymes.
Castelo-Branco
Pedro A
PA
Coordenação de Química, Centro Federal de Educação Tecnológica de Campos, RJ, Brazil.
Rubinger
Mayura M M
MM
Guilardi
Silvana
S
Leite
Vanessa M
VM
dos Santos
Adeliane R
AR
de C Alves
Leandro
L
Lariucci
Carlito
C
Vencato
Ivo
I
Piló-Veloso
Dorila
D
Zambolim
Laércio
L
D020231:Colletotrichum / Q000187:drug effects; D005659:Fungicides, Industrial / Q000737:chemistry* / Q000494:pharmacology*; D007783:Lactones / Q000737:chemistry* / Q000494:pharmacology*; D008958:Models, Molecular; D015394:Molecular Structure
D005659:Fungicides, Industrial; D007783:Lactones; C100081:avenaciolide