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Synthesis and biological activities of novel pyrimidine derivatives of 4,5-didehydro-5,6-dideoxy-L-ascorbic acid

The new pyrimidine derivatives of 2, 3-O, O-dibenzyl-6-deoxy-L-ascorbic acid (8-10) were synthesised by condensation of uracil and its 5-fluoro and 5-trifluoromethyl substituted derivatives with 4-(5, 6-epoxypropyl)-2, 3-O, O-dibenzyl-L-ascorbic acid (7), while pyrimidine derivatives of 4, 5-didehydro-5, 6-dideoxy-L-ascorbic acid (14-17) with free C-2' and C-3' hydroxy groups in the lactone ring were obtained by debenzylation of 11-13 with boron trichloride. Z-Configuration of the C-(4')=C(5') double bond and position of the benzyl group in the lactone ring of 14 were deduced from their 1H and 13C NMR spectra and connectivities in COSY, ROESY and HMBC spectra. The exact stereostructure of 13 was confirmed by its X-ray crystal structure analysis. Of all compounds in the series, the compound 16 containing 5-fluoro-substituted uracil ring showed the most significant antitumor activities against murine leukemia L1210/0 (IC_50 = 1.4 microg/mL), murine mammary carcinoma FM3A/0 (IC_50 = 0.78 microg/mL) and, to a lesser extent, human T-lymphocyte cells Molt4/C8 (IC_50= 31.8 microg/mL) and CEM/0 cell lines (IC-_50 = 20.9 microg/mL)

pyrimidine derivatives of 2 ; 3-O ; O-dibenzyl-6-deoxy-L-ascorbic acid and 4 ; 5-didehydro-5 ; 6-dideoxy-L-ascorbic acid ; synthesis ; antitumor activities

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