engleski

Synthesis And Biological Evaluation Of Novel Pyrimidine And Purine Derivatives Of L-Ascorbic Acid

The pyrimidine derivatives of 2, 3-O, O-dibenzyl-4, 5-didehydro-5, 6-dideoxy-L-ascorbic acid (A) and 2, 3-O, O-dibenzyl-6-deoxy-L-ascorbic acid (B) were synthesized by Vorbrüggen condensation of uracil and its 5-substituted derivatives with 5, 6-O, O-diacetyl-2, 3-O, O-dibenzyl-L-ascorbic acid and 4-(5, 6-epoxypropyl)-2, 3-O, O-dibenzyl-L-ascorbic acid, respectively. The purine derivatives of L-ascorbic acid (C) were obtained by condensation of the purine ring with 5-O-acetyl-6-bromo-2, 3-O, O-dibenzyl-L-ascorbic acid. Debenzylation of 2, 3-O, O-dibenzyl derivatives of L-ascorbic acid with boron trichloride gave mono- and/or dihydroxy derivatives (B and C). The stereostructures of compounds 2, 3-O, O-dibenzyl-5, 6-O, O-isopropylidene-L-ascorbic acid and 2, 3-O, O-dibenzyl-6-O-tosyl-L-ascorbic acid were established by its X-ray structural analysis. The absolute configuration of the carbon atoms C4 and C19 in both structures were determined to be R and S. Of all compounds in the series 5-fluoro-4, 5-didehydro-5, 6-dideoxy-L-ascorbic acid showed the most significant antitumor activities against leukemia L1210/0 (IC50= 1.4  g/mL) and murine mammary carcinoma cells FM3A/0 (IC50= 0.78  g/mL). It inhibits selectively the L1210/0 and FM3A/0 tumor cells but not the other ones.1, 2  1 S. Raić-Malić et al ; J. Med. Chem., 1999, 42, 2673-2678.  2 ibid., 2000, 43, 4806-4811

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