Collect. Czech. Chem. Commun. 1985, 50, 393-417

Preparation of analogues of cytosine and 2-pyrimidinone nucleosides and their effect on bacterial (Escherichia coli A 19) cytidine aminohydrolase

Antonín Holýa, Anita Ludzišab, Ivan Votrubaa, Kateřina Šediváa and Helmut Pischelc

a Institute of Organic Chemistry and Biochemistry, Czechoslovak Academy of Sciences, 166 10 Prague 6, Czechoslovakia
b Institute of Organic Synthesis, Academy of Sciences of the Latvian S.S.R., Riga, U.S.S.R.
c Sektion Biowissenschaften-Pharmazie, Karl-Marx-Universitat, Leipzig, G.D.R.


The set of compounds investigated as substrates and inhibitors of bacterial cytidine aminohydrolase (EC consists of cytidine analogues modified in the heterocyclic base or the sugar moiety and analogues of the similar type derived from l-(β-D-ribofuranosyl)-2-pyrimidone (I) and its isomers. The latter group of compounds includes also open-chain derivatives of neutral and acidic character. These compounds were prepared by novel synthetic procedures. Minimum necessary conditions for the structure of an inhibitor of cytidine aminohydrolase from E. coli A 19 include: a heterocyclic system containing an Rf-N-CO-N(H) fragment of a basic character in which Rf denotes a β-D-aldopentafuranoside with a 3-hydroxy group of ribo-configuration; the 5-hydroxy group of the sugar moiety may bear a substituent, except a phosphomonoester function. The heterocyclic base may also bear substituents in positions other than α to the nucleoside bond which do not reduce substantially the basicity of the system and do not change the conformation of the nucleoside molecule.