| Popis: |
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 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. Debenzylation of 2,3-O,O-dibenzyl derivatives of L-ascorbic acid with boron trichloride gave mono- and/or dihydroxy derivatives (A). Z-Configuration of the C(4')=C(5') double bond and position of the benzyl group in the lactone ring of monobenzylated derivatives were deduced from their 1H and 13C NMR spectra and connectivities in COSY, ROESY and HMBC spectra. Of all compounds in the series 5-fluoro-2,3-O,O-dibenzyl-4,5-didehydro-5,6-dideoxy-L-ascorbic acid showed the most significant antitumor activities against leukemia L1210/0 (IC50=1.4 g/mL), murine mammary carcinoma FM3A/0 (IC50=0.78 g/mL) and in a less extent, human T-lymphocyte cells Molt4/C8 (IC50=31.8 g/mL) and CEM/0 cell lines (IC50=20.9 g/mL). This compound was also the most selective in the citostatic activity. It inhibits selectively the L1210/0 and FM3A/0 tumor cells but not the other ones.1, 2 1 S. Raic-Malic, A. Hergold-Brundic, A. Nagl, M. Grdisa, K. Pavelic, E. De Clercq and M. Mintas, J. Med. Chem. (1999), 42, 2673-2678. 2 S. Raic-Malic, D. Svedruzic, T. Gazivoda, A. Hergold-Brundic, A. Nagl, J. Balzarini, E. De Clercq and M. Mintas, J. Med. Chem. (2000), 43, 4806-4811. |
