Kim Hea Ok, Yoo Su Jeong, Ahn Hee Sung, Choi Won Jun, Moon Hyung Ryong, Lee Kang Man, Chun Moon Woo, Jeong Lak Shin
Laboratory of Medicinal Chemistry, College of Pharmacy, Ewha Womans University, Seoul 120-750, South Korea.
Bioorg Med Chem Lett. 2004 May 3;14(9):2091-3. doi: 10.1016/j.bmcl.2004.02.039.
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.
氟代-DHCeA（4）以亲电氟化作为关键步骤，由d-环戊烯酮衍生物5高效合成。发现氟代-DHCeA（4）与DHCeA（3）具有同等效力，但与表现出可逆抑制作用的DHCeA（3）不同，它对酶表现出不可逆抑制作用。从这项研究可知，新制癌菌素A和氟代新制癌菌素A的4(')-羟甲基基团在与酶的活性位点结合中起重要作用。
