A short-step synthesis of orally active carbapenem antibiotic CS-834.
An orally bioavailable carbapenem CS-834, which is a pivaloyloxymethyl (POM) ester-type prodrug and has (R)-5-oxopyrrolidin-3-ylthio moiety at the C-2 position of the 1 beta-methylcarbapenem skeleton, is currently under clinical trial. We accomplished a short-step synthesis of CS-834 by using phosphorus ylide from the intramolecular Wittig-type reaction in the key step for cyclization to the bicyclic carbapenem system. The POM ester group was found to be suitable for the cyclization conditions.
Mori
M
M
Medicinal Chemistry Research Laboratories, Sankyo Co., Ltd., Tokyo, Japan.
Oida
S
S
D015780:Carbapenems / Q000138:chemical synthesis*; D007202:Indicators and Reagents; D009682:Magnetic Resonance Spectroscopy; D011355:Prodrugs / Q000138:chemical synthesis
D015780:Carbapenems; D007202:Indicators and Reagents; D011355:Prodrugs; C107030:CS 834