Enrico Aiello

Synthesis and antimicrobial activity of new 3-(1-R-3(5)-methyl-4-nitroso-1H-5(3)-pyrazolyl)-5-methylisoxazoles.

A number of new 3-(1-R-3(5)-methyl-4-nitroso-1H-5(3)-pyrazolyl)-5-methylisoxazoles 6a-g (7b-f) were synthesized and tested for antibacterial and antifungal activity. Some of these compounds displayed antifungal activity at non-cytotoxic concentrations. Derivative 6c was 9 times more potent in vitro than miconazole and 20 times more selective against C. neoformans. 6c was also 8- and 125-fold more potent than amphotericin B and fluconazole, respectively. None of the compounds was active against bacteria. Preliminary structure-activity relationship (SAR) studies showed that the NO group at position 4 of the pyrazole ring is essential for the activity. Lipophilicity of the pyrazole moiety, N-alkyl chain length and planarity of the two heterocyclic rings appear to play a decisive role in modulating cytotoxicity and antifungal activity.

Protonation of 3-aminopyrroles

Abstract The protonation of 3-aminopyrroles has been investigated using H and 13C n.m.r. spectroscopy. The spectral data are compatible with predominant protonation of the amino group with no evidence for protonation of the pyrrole ring.

Facile synthesis of pyrazoles and pyrroles via thermolysis of tetrazolo[1,5-b]pyridazines, tetrazolo[1,5-a]pyrimidines and tetrazolo[1,5-a]pyridines

Abstract A simple and high yielding preparation of pyrazoles and pyrroles is described. Thermolysis of tetrazolo[1,5- b ]pyridazines, tetrazolo[1,5- a ]pyrimidines and tetrazolo[1,5- a ]pyridines allowed easy ring contraction thus providing a facile preparation of cyanopyrazole and cyanopyrrole heterocycles. Since the cyano group is a versatile precursor of other functionalities, the reaction appears of particular interest for the construction of a variety of pyrazoles and pyrroles. The simple preparation of the starting tetrazole derivatives, the relatively mild conditions employed, and the very short reaction times make this versatile procedure of great synthetic utility and applicable both to small and large scale preparation.

3-Triazenoindoles. Synthesis and antileukemic activity

Abstract Triazenoindoles of type 3 were synthesized in excellent yields by coupling the 3-diazoindole 1 with the suitable amines. The 3-triazenoindoles 3a-c and the 3-diazoindole 1 showed good cytotoxic activity in vitro against erythroleukemia and multi-drug-resistant cells, with IC50 values in the range 0.053-0.080 μM and 0.10-0.34 μM, respectively.

From ascorbigens to indolocarbazoles

Abstract New methods of l -ascorbic acid derivatization with the use of polyfunctional indole-3-cabinols are described. Reaction of β-hydroxy- N -methyltryptamine and l -ascorbic acid gave lactame derivatives; (indol-3-yl)glycolic and l -ascorbic acids produced 2-hydroxy-4-hydroxymethyl-3-(indol-3-yl)-cyclopen-2-enone. Similarly, 4-hydroxy-3-methoxyphenylglycolic and l -ascorbic acids yielded 2-hydroxy-3-(4-hydroxy-3-methoxyphenyl)-4-hydroxymethyl-cyclopen-2-enone. Properties of N -methoxyascorbigen (neoascorbigen) were investigated. Alkylation of l -ascorbic acid with polysubstituted pyrrolecarbinols led to pyrrole analogues of ascorbigen. Acidic transformation of 3-formylindole and 1-methyl-3-formylindole led to indolocarbazoles and triindolylmethane derivatives.

Polycondensed Nitrogen Heterocycles. Part 26. Aminopyrrolo[1,2-f]phenanthridines by Decomposition and Cyclization of 2-Aryl-1-(3-azidophenyl)pyrroles

Acid catalyzed decomposition of 1-(3-azidophenyl)pyrroles (8a-d) afforded the 6-amino- and 8-aminopyrrolo[1,2-f]phenanthridines of type (11) and (12) through cyclization of the intermediate protosolvated arylnitrenium ions (9). In the case of azide (8a, b) intermolecular side-reactions led also to the hydroxyphenyl derivatives (10)

Synthesis of 3-Triazenopyrroles

Abstract The 3-triazenopyrroles, a new class of pyrrole derivatives, were synthesized in quantitative yield by coupling 3-diazopyrroles with secondary amines.

3-Diazopyrroles—IV. Structure determination using 13C NMR spectroscopy

Abstract On the basis of the 13 C NMR chemical shifts, it is proposed that, although b is the major canonical structure, structure c , in which a negative charge resides at C-3, provides an important contribution to the resonance stabilization of the 3-diazopyrroles, 1–4 .

Polycondensed nitrogen heterocycles. Part 8. Pyrrolo[3,2-b]indole

The reduction of the nitro-derivatives (4a–c) with iron–acetic acid leads to the pyrrolo[3,2-b]indoles (7a–c). This unusual indolization, in which displacement of the heterocycle amino-group occurs, is regarded as a nucleophilic attack by the 2-aminophenyl group on the pyrrole ring, and is an interesting example of intramolecular nucleophilic substitution in the pyrrole series.

Polycondensed nitrogen heterocycles. VI. Pyrrolo[3,4-b]-1,4-thiazine. A new heterocyclic ring system

This paper describes the synthesis of a new ring system, pyrrolo[3,4-b]-1,4-thiazine, obtained via H III IV.