The Synthesis, Cytostatic and Antiviral Evaluations of The Novel C-5 Substituted Pyrimidine and Purine Derivatives of L-ascorbic Acid

The syntheses of the novel C-5 substituted pyrimidine derivatives of L-ascorbic acid containing free hydroxy groups at C-2' (6-10) or C-2' and C-3' (11-15) positions of the lactone ring are described. Debenzylation of the 6-chloro- and 6-(N-pyrrolyl)purine derivatives of 2, 3-O, O-dibenzyl-L-ascorbic acid (16 and 17) gave the new compounds containing hydroxy groups at C-2' (18), and C-2' and C-3' (19 and 20).1, 2 The novel series of the uracil L-ascorbic acid derivatives (21a-j) containing substituents at position 5 which are conjugated with uracil moiety were synthesized by Stille reaction, i.e. the palladium catalyzed coupling of organotin compounds with unsaturated carbon electrophiles. The compound 15 containing 5-(trifluoromethyl)uracil showed marked inhibitory activity against all human malignant cell lines (IC50: 5.6 – 12.8  M) except on human T-lymphocytes. Besides, this compound influenced the cell cycle by increasing the cell population in G2/M phase and induced apoptosis in SW 620 and MiaPaCa-2 cells. The compound 18 containing 6-chloropurine ring expressed the most pronounced inhibitory activities against HeLa (IC50: 6.8  M) and MiaPaCa-2 cells (IC50: 6.5  M).