Synthesis of fluorinated cyclopentenyladenine as potent inhibitor of S-adenosylhomocysteine hydrolase

Abstract

Fluoro-DHCeA (4) was efficiently synthesized from D-cyclopentenone derivative 5 using electrophilic fluorination as a key step. Fluoro-DHCeA (4) was found to be as potent as DHCeA (3), but exhibited irreversible inhibition of enzyme unlike DHCeA (3) showing reversible inhibition. From this study, 4 ′-hydroxymethyl groups of neplanocin A and fluoro-neplanocin A played an important role in binding to the active site of the enzyme. © 2004 Elsevier Ltd. All rights reserved.