Synthesis and Antitumor Activities of Novel Pyrimidine Derivatives of 2,3-O,O-Dibenzyl-6-deoxy-<SCP>l</SCP>-ascorbic Acid and 4,5-Didehydro-5,6- dideoxy-<SCP>l</SCP>-ascorbic Acid

The new pyrimidine derivatives of 2,3-O,O-dibenzyl-6-deoxy-<SCP>l</SCP>-ascorbic acid (<BO>8</BO>−<BO>10</BO>) were synthesized by condensation of uracil and its 5-fluoro- and 5-trifluoromethyl-substituted derivatives with 4-(5,6-epoxypropyl)-2,3-O,O-dibenzyl-<SCP>l</SCP>-ascorbic acid (<BO>7</BO>), while pyrimidine derivatives of 4,5-didehydro-5,6-dideoxy-<SCP>l</SCP>-ascorbic acid (<BO>14</BO>−<BO>17</BO>) with free C-2‘ and C-3‘ hydroxy groups in the lactone ring were obtained by debenzylation of <BO>11</BO>−<BO>13</BO> with boron trichloride. Z-Configuration of the C4‘&dbd;C5‘ double bond and position of the benzyl group in the lactone ring of <BO>14</BO> were deduced from their ¹H and ¹³C NMR spectra and connectivities in COSY, ROESY, and HMBC spectra. The exact stereostructure of <BO>13</BO> was confirmed by its X-ray crystal structure analysis. Of all the compounds in the series, compound <BO>16</BO> containing a 5-fluoro-substituted uracil ring showed the most significant antitumor activities against murine leukemia L1210/0 (IC<INF>50</INF> = 1.4 μg/mL), murine mammary carcinoma FM3A/0 (IC<INF>50</INF> = 0.78 μg/mL), and, to a lesser extent, human T-lymphocyte cells Molt4/C8 (IC<INF>50</INF> = 31.8 μg/mL) and CEM/0 cell lines (IC<INF>50</INF> = 20.9 μg/mL).