Enantioselective fluorination mediated by N-fluoroammonium salts of cinchona alkaloids: first enantioselective synthesis of BMS-204352 (MaxiPost).
We have employed a cinchona alkaloid/Selectfluor-mediated enantioselective fluorination of the oxindole 2 to achieve the first enantioslective synthesis of BMS-204352 (MaxiPost, S-1), an effective opener of maxi-K channels. Fluorination occurred to produce S-1 with 84% ee using the bis-cinchona alkaloid (DHQ)(2)AQN. Recrystallization produced enantiomerically pure (>99% ee) product. Quinidine-mediated fluorination of 2 gave the (R)-antipode of 1 with 68% ee.
Shibata
Norio
N
Faculty of Pharmaceutical Sciences, Toyama Medical and Pharmaceutical University, Sugitani 2630, Toyama 930-0194, Japan. nozshiba@ms.toyama-mpu.ac.jp
Ishimaru
Takehisa
T
Suzuki
Emiko
E
Kirk
Kenneth L
KL
D002384:Catalysis; D002930:Cinchona Alkaloids / Q000737:chemistry*; D015195:Drug Design; D005461:Fluorine / Q000737:chemistry*; D007202:Indicators and Reagents; D007211:Indoles / Q000138:chemical synthesis*; D009682:Magnetic Resonance Spectroscopy; D015394:Molecular Structure; D000644:Quaternary Ammonium Compounds / Q000737:chemistry*; D013237:Stereoisomerism
C424388:BMS204352; D002930:Cinchona Alkaloids; D007202:Indicators and Reagents; D007211:Indoles; D000644:Quaternary Ammonium Compounds; D005461:Fluorine