Nucleosides and nucleotides .150. Enzymatic synthesis of 5'-phosphatidyl derivatives of 1-(2-C-cyano-2-deoxy-beta-D-arabino-pentofuranosyl) (CNDAC) and their notable antitumor effects in mice

1-(2-C-Cyano-2-deoxy-beta-D-arabino-pentofuranosyl)cytosine (CNDAC, 1) is a potent antitumor nucleoside developed by us. A series of 5'-phosphatidyl derivatives of CNDAC bearing various fatty acyl residues, namely dimyristoyl derivative 3a, dipalmitoyl derivative 3b, distearoyl 3c, dioleoyl derivative 3d, and dilinoleoyl derivative 3e, was synthesized by phospholipase D-catalyzed transphosphatidylation. All of these 5'-phosphatidyl-CNDACs (3a-e) administered ip almost perfectly inhibited the growth of sc-implanted M5076 sarcoma in mice, and the effects were clearly superior to that of CNDAC. (C) 1996 Elsevier Science Ltd.