Synthesis of fluorinated cyclopentenyladenine as potent inhibitor of S-adenosylhomocysteine hydrolase.
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.
Kim
Hea Ok
HO
Laboratory of Medicinal Chemistry, College of Pharmacy, Ewha Womans University, Seoul 120-750, South Korea.
Yoo
Su Jeong
SJ
Ahn
Hee Sung
HS
Choi
Won Jun
WJ
Moon
Hyung Ryong
HR
Lee
Kang Man
KM
Chun
Moon Woo
MW
Jeong
Lak Shin
LS
D000225:Adenine / Q000031:analogs & derivatives* / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D043383:Adenosylhomocysteinase / Q000037:antagonists & inhibitors*; D003517:Cyclopentanes / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D005461:Fluorine / Q000737:chemistry*; D009682:Magnetic Resonance Spectroscopy
D003517:Cyclopentanes; D004791:Enzyme Inhibitors; C494075:cyclopentenyladenine; D005461:Fluorine; D043383:Adenosylhomocysteinase; D000225:Adenine