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Syntheses of isoxazoline-carbocyclic nucleosides and their antiviral evaluation: a standard protocol.

Quadrelli P, Vazquez Martinez N, Scrocchi R, Corsaro A, Pistarà V - ScientificWorldJournal (2014)

Bottom Line: Improved yields were obtained by the proper tuning of the single synthetic steps, opening the way for the preparation of a variety of novel compounds.No specific antiviral activity was observed in the cases at hand.Novel compounds were prepared for future biological tests.

View Article: PubMed Central - PubMed

Affiliation: Dipartimento di Chimica, Università degli Studi di Pavia, Viale Taramelli 12, 27100 Pavia, Italy.

ABSTRACT
The current synthesis of racemic purine and pyrimidine isoxazoline-carbocyclic nucleosides is reported, detailing the key-steps for standard and reliable preparations. Improved yields were obtained by the proper tuning of the single synthetic steps, opening the way for the preparation of a variety of novel compounds. Some of the obtained compounds were also evaluated against a wide variety of DNA and RNA viruses including HIV. No specific antiviral activity was observed in the cases at hand. Novel compounds were prepared for future biological tests.

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Related in: MedlinePlus

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Mentions: The HDA cycloadduct N-benzoyl-2,3-oxazanorborn-5-ene 8 was obtained from freshly distilled cyclopentadiene 6 (2 equivalents) that quantitatively trapped the nitrosocarbonyl benzene 7 generated in situ through the mild oxidation of benzonitrile oxide Ph-CNO (BNO) in CH2Cl2 with a slight excess (1.3 equivalents) of N-methyl-morpholine N-oxide (NMO) according to the published procedure (Scheme 1) [18, 19] in good yields (73%). It is essential not to exceed with the NMO amounts in this preparation because a larger excess of the oxidant could be detrimental for the nitrosocarbonyl intermediate's life, since the N-oxide could add the intermediate and promote its decomposition [16, 18, 19]. In Scheme 1 the decomposition pathway is sketched. Nitrosocarbonyls are in fact short-living species, just 180 μs as reported by Cohen and coworkers [20] and, if not instantly trapped, can add the excess NMO to give the intermediate 7i that evolves to add nucleophilic species which can be present in the reaction mixtures even in small amounts to afford N-methylmorfoline, N2O, and the adduct between the benzoyl group and the nucleophile Nu (in case of water, benzoic acid) [21].


Syntheses of isoxazoline-carbocyclic nucleosides and their antiviral evaluation: a standard protocol.

Quadrelli P, Vazquez Martinez N, Scrocchi R, Corsaro A, Pistarà V - ScientificWorldJournal (2014)

© Copyright Policy - open-access
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC4230217&req=5

Mentions: The HDA cycloadduct N-benzoyl-2,3-oxazanorborn-5-ene 8 was obtained from freshly distilled cyclopentadiene 6 (2 equivalents) that quantitatively trapped the nitrosocarbonyl benzene 7 generated in situ through the mild oxidation of benzonitrile oxide Ph-CNO (BNO) in CH2Cl2 with a slight excess (1.3 equivalents) of N-methyl-morpholine N-oxide (NMO) according to the published procedure (Scheme 1) [18, 19] in good yields (73%). It is essential not to exceed with the NMO amounts in this preparation because a larger excess of the oxidant could be detrimental for the nitrosocarbonyl intermediate's life, since the N-oxide could add the intermediate and promote its decomposition [16, 18, 19]. In Scheme 1 the decomposition pathway is sketched. Nitrosocarbonyls are in fact short-living species, just 180 μs as reported by Cohen and coworkers [20] and, if not instantly trapped, can add the excess NMO to give the intermediate 7i that evolves to add nucleophilic species which can be present in the reaction mixtures even in small amounts to afford N-methylmorfoline, N2O, and the adduct between the benzoyl group and the nucleophile Nu (in case of water, benzoic acid) [21].

Bottom Line: Improved yields were obtained by the proper tuning of the single synthetic steps, opening the way for the preparation of a variety of novel compounds.No specific antiviral activity was observed in the cases at hand.Novel compounds were prepared for future biological tests.

View Article: PubMed Central - PubMed

Affiliation: Dipartimento di Chimica, Università degli Studi di Pavia, Viale Taramelli 12, 27100 Pavia, Italy.

ABSTRACT
The current synthesis of racemic purine and pyrimidine isoxazoline-carbocyclic nucleosides is reported, detailing the key-steps for standard and reliable preparations. Improved yields were obtained by the proper tuning of the single synthetic steps, opening the way for the preparation of a variety of novel compounds. Some of the obtained compounds were also evaluated against a wide variety of DNA and RNA viruses including HIV. No specific antiviral activity was observed in the cases at hand. Novel compounds were prepared for future biological tests.

Show MeSH
Related in: MedlinePlus