Synthesis of Novel N-9-Substituted Purine Derivatives from Polymer Supported alpha-Amino Acids

0447320 - ÚEB 2016 RIV US eng J - Journal Article
Vanda, D. - Jorda, Radek - Lemrová, B. - Volná, T. - Kryštof, Vladimír - McMaster, C. - Soural, M.
Synthesis of Novel N-9-Substituted Purine Derivatives from Polymer Supported alpha-Amino Acids.
ACS Combinatorial Science. Roč. 17, č. 7 (2015), s. 426-432. ISSN 2156-8952. E-ISSN 2156-8944
R&D Projects: GA MŠMT(CZ) LO1204; GA MŠMT(CZ) LO1304
Institutional support: RVO:61389030
Keywords : alpha-amino acids * solid-phase synthesis * purine derivatives
Subject RIV: EB - Genetics ; Molecular Biology
Impact factor: 3.317, year: 2015

Solid-phase synthesis of purine derivatives bearing an alpha-amino acid motif in position 9 is described herein. Polymer supported amines were acylated with various Fmoc-alpha-amino acids and, after cleavage of the protecting group, arylation with 4,6-dichloro-5-nitropyrimidine or 2,4-dichloro-5-nitropyrimidine was performed. The second chlorine atom was replaced with various amines. Subsequent reduction of the nitro group, followed by reaction with aldehydes, afforded the purine scaffold. After cleavage from the polymer support, the target compounds were obtained in very good crude purity, good overall yields, and excellent enantiomeric purity. The anticancer activity of prepared compounds was tested in vitro against human cancer cell lines MCF7 and K562, and they were found to have mild, but clear dose-dependent effects.
Permanent Link: http://hdl.handle.net/11104/0249170