IJUP08 - Universidade do Porto

Chiral Alaninol Xanthone Derivatives: Synthesis, Structural
Elucidation and Biological Activities
A. Pinto 1 , C. Fernandes 1,2 , M. Pinto 1,2 , A. Pozzi 3 , B. Matos 3 , L. Oliveira 3 and P. Correiade-Sá
3
1 Department of Organic Chemistry, Faculty of Pharmacy, University of Porto, Portugal.
2 Research Centre of Organic Chemistry, Phytochemistry and Pharmacology of the University of
Porto (CEQOFFUP), Faculty of Pharmacy, University of Porto, Portugal.
3 Unit for Multidisciplinary Investigation in Biomedicine (UMIB), Abel Salazar Biomedical
Sciences Institute (ICBAS), University of Porto, Portugal.
Chiral compounds are of great interest and comprise an area in continuous development in
Medicinal Chemistry [1]. Considering the group of compounds of the chemical family of
xanthone derivatives, there is a large variety of natural and synthetic compounds, described
in the literature [2] but only a few examples with a chiral moiety [3]. Some of these
compounds, namely chiral aminoalkanolic derivatives, have demonstrated important
activities in the central nervous system (CNS), with the available data suggesting potential
antiepileptic and antidepressant activities [3].
In this presentation it is shown the synthesis of two chiral aminoalkanolic derivatives by
the connection of the 2-carboxy-6-methoxyxanthone (1), as building block, with both
enantiomers (S and R) of the amino alcohol alaninol (Fig. 1). These reactions were carried
out with the coupling reagent O-(benzotriazol-1-yl)-N-N-N’-N’-tetramethyluronium
tetrafluoroborate (TBTU).
MeO
O
O
O
OH
TBTU,THF, triethylamine
(S)-(+)-2-alaninol
(1)
TBTU,THF, triethylamine
(R)-(-)-2-alaninol
MeO
O
Fig. 1: Synthesis of chiral alaninol xanthone derivatives (2) and (3) (3).
Considering compound (1), as building block, the expected compounds for a similar
reaction are 2 and 3 (Fig. 1) and their structure will be established by spectroscopic
methods ( 1 H NMR, 13 C NMR, IV and mass spectrometry) and also will be evaluated for
enantiomeric purity. Preliminary pharmacological tests concerning sciatic nerve
conduction experiments [4] were developed and suggest that this family of compounds is
potentially interesting. These preliminary results will be presented in this meeting by
Matos and collaborators. We expect that the synthesis of these new chiral xanthone
derivaties will result in the discovery of some “hit compounds” with important activities in
the central nervous system.
[1] Caner, H., Groner E., Levy L. (2004) Drug Discovery Today, 9 (3), 105-110; [2] Pinto,
M.M.M. et al. (2005), Current Medicinal Chemistry, 12, 2517-2538; [3] Jastrebska-Wiesek, M.,
Librowski, T., Czarnecki, R., Marona, H. and Nowak, G. (2003), Polish Journal of Pharmacology,
55, 461-465; [4] Mert et al., (2003), Pharmacology, 69, 68-73.
Acknowledgements: FCT (I&D, nº226/94), FEDER, POCI, U. Porto, and Caixa Geral de Depósitos
for financial support.
MeO
(2)
O
O
O
O
O
N
H
N
H
OH
OH
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