Synthetic study on novel immunosuppressant KF20444.
The two new synthetic routes to 6,7-dihydro-10-fluoro-3-(2-fluorophenyl)-5H- benzo[6,7]cyclohepta[1,2-b]-quinoline-8-carboxylic acid (1), a novel immunosuppressant KF20444, are described. The seven-membered ring construction from 2-[4-(2-fluorophenyl)phenyl]-3-(2-carboxyethyl)-4-chloromethyl-6-fluoroquinoline (17c) was achieved by intramolecular Friedel-Crafts reaction under acidic conditions as the key step. Subsequently, the oxidation of 4-chloromethyl group followed by reduction of carbonyl group on the seven-membered ring afforded 1. This route provides a new method for the synthesis of 1.
Chujo
I
I
Sakai Research Laboratories, Kyowa Hakko Kogyo Co., Ltd., 1-1-53, Takasu-cho, Sakai, Osaka 590-8554, Japan. iwao.chujo@kyowa.co.jp
Masuda
Y
Y
Fujino
K
K
Kato
S
S
Ogasa
T
T
Mohri
S
S
Kasai
M
M
D001671:Biochemistry / Q000379:methods*; D001713:Biphenyl Compounds / Q000138:chemical synthesis*; D007166:Immunosuppressive Agents / Q000138:chemical synthesis*
D001713:Biphenyl Compounds; D007166:Immunosuppressive Agents; C118187:KF 20444