title: Enantioselective Synthesis and Profiling of Two Novel Diazabicyclooctanone β-Lactamase Inhibitors.
abstract: The enantioselective synthesis of two novel cyclopropane-fused diazabicyclooctanones is reported here. Starting from butadiene monoxide, the key enone intermediate 7 was prepared in six steps. Subsequent stereoselective introduction of the cyclopropane group and further transformation led to compounds 1a and 1b as their corresponding sodium salt. The great disparity regarding their hydrolytic stability was rationalized by the steric interaction between the cyclopropyl methylene and urea carbonyl. These two novel β-lactamase inhibitors were active against class A, C, and D enzymes.
authors.affiliation: Infection Innovative Medicines, AstraZeneca Pharmaceuticals , 35 Gatehouse Drive, Waltham, Massachusetts 02451, United States.
authors.forename: Hui
authors.initials: H
authors.lastname: Xiong
authors.affiliation: Infection Innovative Medicines, AstraZeneca Pharmaceuticals , 35 Gatehouse Drive, Waltham, Massachusetts 02451, United States.
authors.forename: Brendan
authors.initials: B
authors.lastname: Chen
authors.affiliation: Infection Innovative Medicines, AstraZeneca Pharmaceuticals , 35 Gatehouse Drive, Waltham, Massachusetts 02451, United States.
authors.forename: Thomas F
authors.initials: TF
authors.lastname: Durand-Réville
authors.affiliation: Infection Innovative Medicines, AstraZeneca Pharmaceuticals , 35 Gatehouse Drive, Waltham, Massachusetts 02451, United States.
authors.forename: Camil
authors.initials: C
authors.lastname: Joubran
authors.affiliation: Infection Innovative Medicines, AstraZeneca Pharmaceuticals , 35 Gatehouse Drive, Waltham, Massachusetts 02451, United States.
authors.forename: Yun W
authors.initials: YW
authors.lastname: Alelyunas
authors.affiliation: Infection Innovative Medicines, AstraZeneca Pharmaceuticals , 35 Gatehouse Drive, Waltham, Massachusetts 02451, United States.
authors.forename: Dedong
authors.initials: D
authors.lastname: Wu
authors.affiliation: Infection Innovative Medicines, AstraZeneca Pharmaceuticals , 35 Gatehouse Drive, Waltham, Massachusetts 02451, United States.
authors.forename: Hoan
authors.initials: H
authors.lastname: Huynh
keywords: asymmetric synthesis; hydrolytic stability; β-lactamase inhibitor