Nucleosides and nucleotides. 150. Enzymatic synthesis of 5′-phosphatidyl derivatives of [formula omitted] (CNDAC) and their notable antitumor effects in mice 1

Abstract

1-(2-C- Cyano-2-deoxy-β- 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.