The isoxazolidine ring represents one of the privileged structures in medicinal chemistry, and there have been an increasing number of studies on isoxazolidine and isoxazolidine-containing compounds. Optimization of the 1,3-dipolar cycloaddition (1,3-DC), original methods including electrophilic or palladium-mediated cyclization of unsaturated hydroxylamine, has been developed to obtain isoxazolidines. Novel reactions involving the isoxazolidine ring have been highlighted to accomplish total synthesis or to obtain bioactive compounds, one of the most significant examples being probably the thermic ring contraction applied to the total synthesis of (±)-Gelsemoxonine. The unique isoxazolidine scaffold also exhibits an impressive potential as a mimic of nucleosides, carbohydrates, PNA, amino acids, and steroid analogs. This review aims to be a comprehensive and general summary of the different isoxazolidine syntheses, their use as starting building blocks for the preparation of natural compounds, and their m...

Isoxazolidine: A Privileged Scaffold for Organic and Medicinal Chemistry

In the present perspective the advances and real possibilities of 1,3-dipolar cycloadditions as key steps in the total synthesis of virus inhibitors are described. Azides, nitrones, and azomethine ylides are the most appropriate 1,3-dipoles for the synthesis of privileged structures with the highest biological responses against viruses.

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1,3-Dipolar cycloadditions: applications to the synthesis of antiviral agents.

A novel organocatalytic formal [3 + 2] cycloaddition reaction with in situ generation of N-carbamoyl nitrones is presented. For the first time, N-Boc- and N-Cbz-protected isoxazolidines have been directly obtained as single diastereoisomers in generally high yields and enantiomeric excesses using mild reaction conditions and inexpensive, readily available Cinchona alkaloid quaternary ammonium salts as catalysts. Synthetic manipulations of the products provided highly valuable building blocks such as free isoxazolidines, a N-Boc-1,3-aminoalcohol, and a free delta-lactam. This report represents a pioneering work in the use of N-carbamoyl nitrones as electron-poor 1,3-dipoles and glutaconates as new dipolarophiles in asymmetric catalysis.

Organocatalytic asymmetric formal [3 + 2] cycloaddition with in situ-generated N-carbamoyl nitrones.

Microwave‐Assisted 1,3‐Dipolar Cycloaddition: an Eco‐Friendly Approach to Five‐Membered Heterocycles

Antiviral activity of seed extract from Citrus bergamia towards human retroviruses

Phosphonated carbocyclic 2'-oxa-3'-aza-nucleosides have been synthesized in good yields by 1,3-dipolar cycloaddition methodology. The cytotoxicity and the reverse transcriptase inhibitory activity of the obtained compounds have been investigated. Phosphonated carbocyclic 2'-oxa-3'-aza-nucleosides, while showing low levels of cytotoxicity, exert a specific inhibitor activity on two different reverse transcriptases, which is comparable with that of AZT, opening new perspectives on their possible use as therapeutic agents, in anti-retroviral and anti-HBV chemotherapy.

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Synthesis of phosphonated carbocyclic 2'-oxa-3'-aza-nucleosides: novel inhibitors of reverse transcriptase.

Phosphonated carbocyclic 2‘-oxa-3‘-azanucleosides have been synthesized and tested for their antiretroviral activity. The obtained results have shown that some of the compounds were as powerful as azydothymidine in inhibiting the reverse transcriptase activity of the human retrovirus T-cell leukemia/lymphotropic virus type 1 and in protecting human peripheral blood mononuclear cells against human retrovirus T-cell leukemia/lymphotropic virus type 1 transmission in vitro. These data indicate that phosphonated carbocyclic 2‘-oxa-3‘-azanucleosides possess the necessary requirements to efficiently counteract infections caused by human retroviruses.

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Phosphonated carbocyclic 2'-oxa-3'-azanucleosides as new antiretroviral agents.

The present invention relates to the use in the medical field of 2-oxo-2H-pyrrol- 1 (5)-carboxamide derivatives in the treatment of HIV infections, pharmaceutical compositions containing these derivatives as active ingredients, and a process for the preparation of such derivatives.

Roberto Romeo

Papers

Synthesis of phosphonated carbocyclic 2'-oxa-3'-aza-nucleosides: novel inhibitors of reverse transcriptase.

Phosphonated carbocyclic 2'-oxa-3'-azanucleosides as new antiretroviral agents.

Use of 2-oxo-2h-pyrrol-1(5h)-carboxamide derivatives as anti-hiv agents and process for the production thereof

Uso di derivati 2-oxo-2h-pirrol-1(5h)-carbossamidicicome agenti anti-hiv e processo per la loroproduzione