1. Efficient Electrochemical N-Alkylation of N-Boc-Protected 4-Aminopyridines: Towards New Biologically Active Compounds
- Author
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Feroci, Marta, Chiarotto, Isabella, Forte, Gianpiero, Simonetti, Giovanna, D'Auria, Felicia Diodata, Diodata, Maes, Louis, Scipione, Luigi, Friggeri, Laura, DI SANTO, Roberto, DE VITA, Daniela, and Tortorella, Silvano
- Subjects
chemistry.chemical_classification ,4-aminopyridines ,Article Subject ,Chemistry ,medicine.drug_class ,antiprotozoal activity ,antifungal activity ,Halide ,Biological activity ,Alkylation ,electrochemical N-alkylation ,Medicinal chemistry ,Antiprotozoal ,medicine ,Reactivity (chemistry) ,Human medicine ,Counterion ,Biology ,Alkyl ,Aminopyridines ,Research Article - Abstract
The use of electrogenerated acetonitrile anion allows the alkylation of N-Boc-4-aminopyridine in very high yields, under mild conditions and without by-products. The high reactivity of this base is due to its large tetraethylammonium counterion, which leaves the acetonitrile anion “naked.” The deprotection of the obtained compounds led to high yields in N-alkylated 4-aminopyridines. Nonsymmetrically dialkylated 4-aminopyridines were obtained by subsequent reaction of monoalkylated ones with t-BuOK and alkyl halides, while symmetrically dialkylated 4-aminopyridines were obtained by direct reaction of 4-aminopyridine with an excess of t-BuOK and alkyl halides. Some mono- and dialkyl-4-aminopyridines were selected to evaluate antifungal and antiprotozoal activity; the dialkylated 4-aminopyridines 3ac, 3ae and 3ff showed antifungal towards Cryptococcus neoformans; whereas 3cc, 3ee and 3ff showed antiprotozoal activity towards Leishmania infantum and Plasmodium falciparum.
- Published
- 2014
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