IJUP08 - Universidade do Porto

MeO
Synthesis, Structural Elucidation and Biological Activities of
Chiral 1-Amino-2-Propanol Xanthone Derivatives
O
O
(1)
O
I. Teixeira 1 , M. Pinto 1,2 and C. Fernandes 1,2
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.
There is a large variety of natural and synthetic xanthone derivatives described in the
literature [1] but only a few examples with a chiral moiety [2]. Previous research has
shown that chiral xanthones, namely chiral aminoalkanolic derivatives, present a sort of
pharmacological activities, such as anticonvulsant and antidepressant activities [2].
Our research group (CEQOFFUP) has a large experience in synthesis of xanthones with
interesting biological activities, namely among then a chiral xanthone obtained by the
condensation of 2-carboxy-6-methoxyxanthone with the aminoalcohol L-valinol.
In this presentation it is shown the synthesis of new chiral aminoalkanolic derivatives by
the connection of the same building block (1), with two amino alcohols. The xanthone (1)
was bonded to (R)-(-)-1-amino-2-propanol and (S)-(+)-1-amino-2-propanol to give the
chiral derivatives 2 and 3 (Fig. 1). These reactions were carried out with the coupling
reagent O-(benzotriazol-1-yl)-N-N-N’-N’-tetramethyluronium tetrafluoroborate (TBTU).
OH
N
H 2
1eq TBTU, dry THF
OH
MeO
O
O
(2) or (3)
O
R
(2) R:
(3) R:
Fig. 1: Synthesis of chiral 1-amino-2-propanol xanthone derivatives (2) and (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.
All compounds will be evaluated for their neurological activity on nerve conduction
properties using the sciatic nerve model [3]. We hope that this methodology lead to the
discovery of new chiral compounds with potential antiepileptic activity.
References:
[1] Pinto, M.M.M., Sousa, M.E. and Nascimento, M.S.J. (2005), Xanthone Derivatives: New
Insights in Biological Activity, Current Medicinal Chemistry, 12 (21), 2517-2538.
[2] Marona, H. (1998), Synthesis and anticonvulsant effects of some aminoalkanolic derivatives of
xanthone, Pharmazie, 53, 672-676.
[3] Mert et al., (2003), Differential Effects of Lidocaine and Tramadol on Modified Nerve Impulse
by 4-Aminopyridine in Rats, Pharmacology, 69, 68-73.
Acknowledgments: FCT (I&D, nº226/94), FEDER, POCI for financial support.
NH
NH
OH
OH
CH 3
CH 3
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