著者

石黒 正路 西原 達郎 田中 里枝

出版者

公益社団法人 日本薬学会

雑誌

YAKUGAKU ZASSHI (ISSN:00316903)

巻号頁・発行日

vol.121, no.12, pp.915-927, 2001-12-01 (Released:2002-09-27)

参考文献数

33

被引用文献数

5 8

---

An orally active penem antibiotic, Farom (generic name: faropenem), was designed by the conformational analysis of active and inactive penem derivatives. Faropenem showed potent activity against a wide variety of bacteria including extended-spectrum β-lactamase (ESBL)-producing ones. The mechanism of the stability against ESBL was elucidated by modeling the Michaelis complex of faropenem and Toho-1, an ESBL. Modeling of a complex of faropenem at the active site of a penicillin-binding protein 2 (PBP2) model suggested the characteristic affinity for faropenem with PBP2 of Escherichia coli. Faropenem has been totally synthesized from (R)-1,3-butanediol. The synthetic intermediate, a 3-hydroxyethyl-4-acetoxyazetidinone derivative, was efficiently prepared by the 2+2 coupling of a optically active vinyl-sulfide derivative and chlorosulfonyl isocyanate, followed by the substitution of the acetoxy group for the thiophenyl group at the C-4 position.