The two pairs of enantiomers of isoxazolidin-3-ones 3 and 4 were synthesized by means of Lipase PS-catalyzed hydrolyses of suitable racemic butyrates. The same butyrates were also employed as key intermediates in the preparation of racemic 3 and 4. The antimuscarinic potency of the new compounds was assayed in two in vitro functional tests. The eutomers (-)-3 and (-)-4 share the same stereochemistry (5R) of the most potent enantiomer of `'azamuscarone'' 2, a structurally related muscarinic agonist. Such a spatial arrangement around the chiral center of 2-4, coupled with the low values of eudismic ratio, represents an anomaly among the chiral muscarinic ligands. This anomaly was accounted for by the absence of a chiral center at C-2, a positon whose configuration is crucial in determining the high enantioselectivity of muscarinic agonists and antagonists.

SYNTHESIS AND PHARMACOLOGICAL INVESTIGATION OF NEW CHIRAL MUSCARINIC ANTAGONISTS / M. Carnielli, M. De Amici, C. De Micheli, T. Gianferrara, V. Maurich, M. Zacchigna, E. Grana, C. Boselli. - In: IL FARMACO. - ISSN 0014-827X. - 50:1(1995), pp. 21-27.

SYNTHESIS AND PHARMACOLOGICAL INVESTIGATION OF NEW CHIRAL MUSCARINIC ANTAGONISTS

M. De Amici
Secondo
;
C. De Micheli;
1995

Abstract

The two pairs of enantiomers of isoxazolidin-3-ones 3 and 4 were synthesized by means of Lipase PS-catalyzed hydrolyses of suitable racemic butyrates. The same butyrates were also employed as key intermediates in the preparation of racemic 3 and 4. The antimuscarinic potency of the new compounds was assayed in two in vitro functional tests. The eutomers (-)-3 and (-)-4 share the same stereochemistry (5R) of the most potent enantiomer of `'azamuscarone'' 2, a structurally related muscarinic agonist. Such a spatial arrangement around the chiral center of 2-4, coupled with the low values of eudismic ratio, represents an anomaly among the chiral muscarinic ligands. This anomaly was accounted for by the absence of a chiral center at C-2, a positon whose configuration is crucial in determining the high enantioselectivity of muscarinic agonists and antagonists.
Settore CHIM/08 - Chimica Farmaceutica
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/2434/184428
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