engleski

The New 5- or 6-Azapyrimidine and Cyanuric Acid Derivatives of L-Ascorbic Acid Bearing the Free C-5 Hydroxy or C-4 Amino Group at the Ethylenic Spacer: CD-Spectral Absolute Configuration Determination and Biological Activity Evaluations

Cytosine and azacytosine derivatives of L- ascorbic acid are obtained by the reaction of silylated cytosine bases (I) with ascorbic acid derivatives (II) and (VII) under Vorbrueggen reaction conditions. The products are subjected to either debenzylation reactions or to ammonolysis. Ammonolysis creates a new chiral stereocenter at the C-4 position of the lactone moiety, cf. (VI). These compounds exist as a racemates, whereas ascorbic acid derivatives (VIII) containing the C-5 substituted hydroxy group at the ethylenic spacer, are obtained in enantiomeric form. The pyrimidine, azauracil, and cyanuric acid derivatives are synthesized in an analogous manner. In general, the compounds do not display distinct and specific antiproliferative activity, although derivatives (III) possess pronounced cytostatic activity. (IIIb) is highly cytotoxic to normal human fibroblasts as well.

Pyrimidine and cyanuric acid derivatives ; L-ascorbic acid ; Circular dichroism ; Cytostatic activity evaluation ; X-ray diffraction ; Cell cycle analysis

Abstract published in ChemInform.