Table of Contents
ISRN Organic Chemistry
Volume 2014 (2014), Article ID 621592, 10 pages
http://dx.doi.org/10.1155/2014/621592
Research Article

Efficient Electrochemical N-Alkylation of N-Boc-Protected 4-Aminopyridines: Towards New Biologically Active Compounds

1Department of Basic and Applied Sciences for Engineering, Sapienza University of Rome, Via Castro Laurenziano 7, 00161 Rome, Italy
2Department of Public Health and Infectious Diseases, Sapienza University of Rome, Piazzale Aldo Moro 5, 00185 Rome, Italy
3Laboratory for Microbiology, Parasitology and Hygiene (LMPH), Faculty of Pharmaceutical, Biomedical and Veterinary Sciences, Antwerp University, 2610 Antwerp, Belgium
4“Istituto Pasteur-Fondazione Cenci Bolognetti”, Department of “Chimica e Tecnologie del Farmaco”, Sapienza University of Rome, Piazzale Aldo Moro 5, 00185 Rome, Italy

Received 22 November 2013; Accepted 21 January 2014; Published 5 March 2014

Academic Editors: L. Palombi and R. Pohl

Copyright © 2014 Marta Feroci et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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.