Collect. Czech. Chem. Commun. 2003, 68, 779-791

A Facile Synthesis of 9-Deaza Analogue of Olomoucine

Petr Čapek, Miroslav Otmar*, Milena Masojídková, Ivan Votruba and Antonín Holý

Institute of Organic Chemistry and Biochemistry, Academy of Sciences of the Czech Republic, Flemingovo nám. 2, 166 10 Prague 6, Czech Republic


Heating of 6-(benzylamino)-2-chloro-9-deazapurine (3) with ethanolamine afforded 6-(benzylamino)-2-[(2-hydroxyethyl)amino]-9-deazapurine (8). Its treatment with formaldehyde in alkaline solution, after protection of the OH group with DMTr, led to hydroxymethylation at position 9. Conversion of the hydroxymethyl group to methyl was performed by catalytic hydrogenation under simultaneous deprotection, which resulted in the formation of the 9-deaza analogue 1 of olomoucine. Compound 1 does not exhibit any significant in vitro cell growth inhibition of CCRF-CEM, HeLa and L-1210 cell lines. Cytostatic activity was found in 6-(benzylamino)-9-deazapurine (2) and its 2-chloro derivative 3 in CCRF-CEM cells with IC50 13.3 and 15.8 μM, respectively.

Keywords: Pyrrolo[3,2-d]pyrimidines; 9-Deazapurine; 2a,3,4,5-Tetrahydro-2a,5,6,8-tetraazaacenaphthylene; CDK Inhibitors; Purines; Cytokinins; Antitumor activity; Cytostatics.

References: 17 live references.