The discovery of new pharmacological agents is one of the biggest challenges for chemists. One of these is the synthesis of spiro-isoxazolidines pharmacologically active. In recent years it has been developed the synthesis of spiro compounds by 1,3-dipolar cycloaddition reactions, in which the isoxazolidinic core product is an interesting pharmacophore that could be the future in biology and pharmacology fields. Isoxazolidines are cyclic molecules that mimic natural nucleosides exerting antiviral activity; for example, the furanopirimidine N,O-nucleosides inhibit the replication of DNA and RNA of poliovirus 1. The presence of a nucleobase on the oxazolidine ring leads to the formation of modified N,O-nucleosides which greatly increase the cytotoxicity of these molecules making them excellent candidates as antitumor agents1,2. In addition, the asymmetric character of the molecules that have one or more spiro carbon is one of the most important factors that determine the biological activities3,4. The indole compounds are further relevant since their spiro derivatives are excellent anti-cancer agents, antibiotics, inhibitors of the receptor NK-15 and inhibitors of p53- MDM2 interaction. In this context, the object of this work is the synthesis of a new class of indolyl spiro-isoxazolidine N,O-nucleosides variously functionalized that can enclose all the pharmacological properties of each class of molecules above described. The synthesis of these chiral compounds is carried out with simple and "Solvent-free" methodologies, by diastereoselective and microwave assisted 1,3-dipolar cycloaddition reaction between a chetonitrone derived from 1-indanone and a vinylnucleobase (Scheme 1). The synthetic methodology is innovative in that the two precursors are reacted in the solid phase and without solvent. The reaction products were obtained with high reaction yields and excellent diasteroisomeric ratio. Moreover, all products are been subjected to a subsequent test phase to evaluate the pharmacological activity.

Solvent-Free Synthesis and Characterization of Spiro-isoxazolidines at Potential Biological Activity

NARDI M;
2015

Abstract

The discovery of new pharmacological agents is one of the biggest challenges for chemists. One of these is the synthesis of spiro-isoxazolidines pharmacologically active. In recent years it has been developed the synthesis of spiro compounds by 1,3-dipolar cycloaddition reactions, in which the isoxazolidinic core product is an interesting pharmacophore that could be the future in biology and pharmacology fields. Isoxazolidines are cyclic molecules that mimic natural nucleosides exerting antiviral activity; for example, the furanopirimidine N,O-nucleosides inhibit the replication of DNA and RNA of poliovirus 1. The presence of a nucleobase on the oxazolidine ring leads to the formation of modified N,O-nucleosides which greatly increase the cytotoxicity of these molecules making them excellent candidates as antitumor agents1,2. In addition, the asymmetric character of the molecules that have one or more spiro carbon is one of the most important factors that determine the biological activities3,4. The indole compounds are further relevant since their spiro derivatives are excellent anti-cancer agents, antibiotics, inhibitors of the receptor NK-15 and inhibitors of p53- MDM2 interaction. In this context, the object of this work is the synthesis of a new class of indolyl spiro-isoxazolidine N,O-nucleosides variously functionalized that can enclose all the pharmacological properties of each class of molecules above described. The synthesis of these chiral compounds is carried out with simple and "Solvent-free" methodologies, by diastereoselective and microwave assisted 1,3-dipolar cycloaddition reaction between a chetonitrone derived from 1-indanone and a vinylnucleobase (Scheme 1). The synthetic methodology is innovative in that the two precursors are reacted in the solid phase and without solvent. The reaction products were obtained with high reaction yields and excellent diasteroisomeric ratio. Moreover, all products are been subjected to a subsequent test phase to evaluate the pharmacological activity.
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/20.500.12078/1333
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