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

Hea Ok Kim; Su Jeong Yoo; Hee Sung Ahn; Won Jun Choi; Hyung Ryong Moon; Kang Man Lee; Moon Woo Chun; Lak Shin Jeong

doi:10.1016/j.bmcl.2004.02.039

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

Bioorg Med Chem Lett. 2004 May 3;14(9):2091-3. doi: 10.1016/j.bmcl.2004.02.039.

Authors

Hea Ok Kim¹, Su Jeong Yoo, Hee Sung Ahn, Won Jun Choi, Hyung Ryong Moon, Kang Man Lee, Moon Woo Chun, Lak Shin Jeong

Affiliation

¹ Laboratory of Medicinal Chemistry, College of Pharmacy, Ewha Womans University, Seoul 120-750, South Korea.

PMID: 15080985
DOI: 10.1016/j.bmcl.2004.02.039

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Adenine / analogs & derivatives*
Adenine / chemical synthesis*
Adenine / chemistry
Adenine / pharmacology*
Adenosylhomocysteinase / antagonists & inhibitors*
Cyclopentanes / chemical synthesis*
Cyclopentanes / chemistry
Cyclopentanes / pharmacology*
Enzyme Inhibitors / pharmacology*
Fluorine / chemistry*
Magnetic Resonance Spectroscopy

Substances

Cyclopentanes
Enzyme Inhibitors
cyclopentenyladenine
Fluorine
Adenosylhomocysteinase
Adenine