Synthesis of 5'-substituted fluoro-neplanocin A analogues: importance of a hydrogen bonding donor at 5'-position for the inhibitory activity of S-adenosylhomocysteine hydrolase

Four 5'-substituted fluoro-neplanocin A analogues 1a-d were designed and synthesized, using cyclopentenone derivative 2 as a key intermediate. The inhibitory activity against SAH was in the following order: NH(2)>SH>F, N(3), indicating a hydrogen bonding donor such as OH or NH(2) was essential for inhibitory activity. All the final compounds showed much less decreased cytotoxicity in two cancer cell lines (Col2 and A549), implying that phosphorylation of the 5'-hydroxyl group of fluoro-neplanocin A is closely related to its high cytotoxicity.