An alternative synthesis of 4-amino-3-hydroxy-4,5,6,6a-tetrahydro-3aH- cyclopenta[d]isoxazole-4-carboxylic acid, a conformationally constrained analogue of aspartic acid, is described. The synthetic strategy is based on a regioselective 1,3-dipolar cycloaddition to give the cyclopenta[d]isoxazoline framework; subsequent condensation of this 4-oxocyclopenta[d]isoxazoline with 4-methoxybenzylamine gives a 4-imino derivative, which undergoes a highly stereoselective nucleophilic attack by the cyanide ion. This gives a 4-(methoxybenzylamino)-4-cyano derivative, which is oxidized to the corresponding 4-amino-4-cyano derivative, which itself is transformed into the target 4-carboxylic acid. This amino acid is obtained in 27% overall yield in five steps, whereas the previously described synthetic strategy gave the target derivative in only 0.5% overall yield over 15 steps.

Stereoselective synthesis of 4-amino-3-hydroxy-4,5,6,6a-tetrahydro-3aH-cyclopenta[d]isoxazole-4-carboxylic acid, a conformationally constrained analogue of aspartic acid / P. Conti, A. Pinto, G. Roda, L. Tamborini, D. Arosio, C. De Micheli. - In: SYNTHESIS. - ISSN 0039-7881. - 14:14(2007 Jul 17), pp. 2145-2148. [10.1055/s-2007-983750]

Stereoselective synthesis of 4-amino-3-hydroxy-4,5,6,6a-tetrahydro-3aH-cyclopenta[d]isoxazole-4-carboxylic acid, a conformationally constrained analogue of aspartic acid

P. Conti
Primo
;
A. Pinto
Secondo
;
G. Roda;L. Tamborini;C. De Micheli
Ultimo
2007

Abstract

An alternative synthesis of 4-amino-3-hydroxy-4,5,6,6a-tetrahydro-3aH- cyclopenta[d]isoxazole-4-carboxylic acid, a conformationally constrained analogue of aspartic acid, is described. The synthetic strategy is based on a regioselective 1,3-dipolar cycloaddition to give the cyclopenta[d]isoxazoline framework; subsequent condensation of this 4-oxocyclopenta[d]isoxazoline with 4-methoxybenzylamine gives a 4-imino derivative, which undergoes a highly stereoselective nucleophilic attack by the cyanide ion. This gives a 4-(methoxybenzylamino)-4-cyano derivative, which is oxidized to the corresponding 4-amino-4-cyano derivative, which itself is transformed into the target 4-carboxylic acid. This amino acid is obtained in 27% overall yield in five steps, whereas the previously described synthetic strategy gave the target derivative in only 0.5% overall yield over 15 steps.
1,3-dipolar cycloaddition; Aspartate analogues; Glutamate transporters; Heterocycles; Stereoselective synthesis;
Settore CHIM/08 - Chimica Farmaceutica
17-lug-2007
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2434/39052
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