Practical synthesis of a 1beta-methylcarbapenem, J-111,225, using 4-mercapto-2-[4-(N-methylaminomethyl)phenyl]pyrrolidine as a precursor.
An effective and practical procedure for the synthesis of J-111,225 (1), a new 1beta-methylcarbapenem, was developed using 4-mercapto-2-14-(N-methylaminomethyl)phenyl]pyrrolidine (2a) as a precursor. The coupling reaction of 2a with p-nitrobenzyl (PNB)-protected 1beta-methylcarbapenem enolphosphate 3a and successive removal of PNB group afforded J-111,225 (1) in significantly increased yield compared to the ordinary procedure using a C-2 side-chain thiol with amino-protective groups.
Imamura
H
H
Banyu Tsukuba Research Institute, Banyu Pharmaceutical Co., Ltd., Tsukuba, Ibaraki, Japan. imamrahk@banyu.co.jp
Shimizu
A
A
Sato
H
H
Sugimoto
Y
Y
Sakuraba
S
S
Yamada
K
K
Morishima
H
H
D000890:Anti-Infective Agents / Q000138:chemical synthesis*; D015780:Carbapenems / Q000138:chemical synthesis*; D018360:Crystallography, X-Ray; D007202:Indicators and Reagents; D011759:Pyrrolidines / Q000737:chemistry*
C432959:4-mercapto-2-(4-(N-methylaminomethyl)phenyl)pyrrolidine; D000890:Anti-Infective Agents; D015780:Carbapenems; D007202:Indicators and Reagents; C404721:J 111225; D011759:Pyrrolidines