Francesco Risitano

A convenient synthesis of furo[3,2-c]coumarins by a tandem alkylation/intramolecular aldolisation reaction

Abstract A simple and efficient synthesis of furo[3,2- c ]coumarin derivatives from 4-hydroxycoumarin and α-haloketones via a tandem O -alkylation/cyclisation protocol is described.

First synthesis of a bromonitrilimine. Direct formation of 3-bromopyrazole derivatives

The first example of the preparation of bromonitrilimine 3 is described. This precursor provides a convenient entry to highly regioselective synthesis of 3-bromopyrazole derivatives 4 and 5.

Diastereoselective multicomponent synthesis and anti-HSV-1 evaluation of dihydrofuran-fused derivatives

Enolizable 6-membered cyclic 1,3-dicarbonyls undergo an efficient and diastereoselective domino condensation/addition/heterocyclization reaction with arylaldehydes and phenacyl chloride, producing highly substituted dihydrofuran-fused derivatives. Ring size of the cyclic 1,3-dicarbonyls and the presence of at least one keto group are crucial to the reaction’s success. The new compounds were evaluated in vitro for antiviral activity against herpes simplex virus type-1 (HSV-1). Interestingly, some of them appeared able to interfere with HSV-1 replication, without detection of cytotoxic effects.

Synthesis and anti HSV-1 evaluation of novel indole-3,4-diones

A novel class of water soluble indole-3,4-diones has been synthesized and evaluated in vitro for antiviral activity against HSV-1. The results showed lack of cytotoxicity and significant antiviral activity. The cellular internalization efficiency and the antiherpetic effect were successfully increased by incorporation into nanoaggregates of an amphiphilic β-cyclodextrin.

Direct synthesis of C3-mono-functionalized oxindoles from N-unprotected 2-oxindole and their antileishmanial activity.

A novel approach for the synthesis of unprecedented C3-mono-functionalized indolin-2-ones is reported, starting from 2-oxindole and chalcones. The reactions proceed regioselectively under mild conditions, without di- and tri-alkylated side products. The new compounds have been evaluated in vitro for their antiproliferative effects against the protozoan Leishmania infantum. Interestingly, they appear able to kill L. infantum promastigotes and amastigotes, without significant cytotoxic effects.

Self-Catalyzed Mannich-Type Reaction of Enolizable Cyclic 1,3-Dicarbonyls to Acyclic Nitrones: An Entry to Functionalized β-Enamino Diones

A new method for the preparation of highly functionalized β-enamino diones has been developed. The protocol involves an initial self-catalyzed Mannich-type reaction of enolizable cyclic 1,3-dicarbonyls to nitrones, followed by a spontaneous intramolecular reorganization of the resulting nonisolated hydroxylamine to enamino derivatives. These compounds retain the features of unnatural α-amino acids. The ease of preparation makes them attractive intermediates for the synthesis of peptidomimetics, polyheterocycles, and other multifunctional compounds. All experimental results have been efficiently rationalized by in silico studies at the M06-2X level of theory, and a valid mechanistic pathway has been proposed.

C,C- and C,N-linked dimers and 4-arylmethyl derivatives from 4-arylmethylene pyrazol-5-ones and isoxazol-5-ones with 2-arylbenzim idazolines.

Abstract 2-arylbenzimidazolines (8), generated in situ from o-phenylenediamine (7) and the appropriate arylaldehydes, by reaction with 4-arylmethylene pyrazol-5-ones (1) or isoxazol-5-ones (2) produce the 4-arylmethyl derivatives (3) or (4) and the C,C- (5) or the C,N-linked dimers. The reaction was rationalised on the basis of the role of 2-arylbenzimidazoline as a reducing agent and proceeds by a non-chain, free radical process involving one-electron transfer.

REACTION OF DIAZINES AND THEIR BENZO DERIVATIVES WITH BENZONITRILE OXIDE

Abstract The reaction of diazines 1 and benzodiazines 2 with benzonitrile oxide in refluxing benzene affords regio, site and stereospecific cycloadducts to the diazine ring and/or products derived from them.

Pyridinium N-Ylides and (Arylmethylene)azol-5-ones. Reaction Cascade Leading to an Unusual Spiroisoxazolinone Ring

Abstract The reaction of a series of (arylmethylene)azol-5-ones with phenacylpyridinium salt 3 in glacial acetic acid/ammonium acetate mixture gives different results depending on the starting azolone. The isoxazol-5-ones 1 give the unusual spirans 6 in a reaction cascade involving Michael- and retro-Michael reactions, C-alkylation, aldol addition, and diastereospecific cyclization. The reaction performed with oxazol-5-ones 11 has shown that a literature report has to be corrected since no oxazolopyridines 12 but rather arylideneimidazol-5-ones 13 are produced. In the case of pyrazolin-5-ones 14, the unavoidable formation of bis-adducts 15 always prevents any other type of reaction.

Aldol-type compounds from water-soluble indole-3,4-diones: synthesis, kinetics, and antiviral properties

A straightforward transformation of indole-3,4-diones is reported. The reaction feasibility is evidenced by kinetic studies on a model substrate, revealing a double phase process with a first faster pseudo-first-order step (i.e., deprotonation of the dione and self-nucleophilic attack of the anion) and a subsequent slower dehydration of the intermediate. The overall process is faster at pH higher than the pK value of the investigated substrate. The biological relevance of new compounds has been assessed in vitro against herpes simplex virus type-1 (HSV-1), showing a more promising biological profile with respect to their precursors.