Inhibitors of Bacterial \u3cem\u3eN\u3c/em\u3e-succinyl-L,L-diaminopimelic Acid Desuccinylase (DapE) and Demonstration of in vitro Antimicrobial Activity

The dapE-encoded N-succinyl-L,L-diaminopimelic acid desuccinylase (DapE) is a critical bacterial enzyme for the construction of the bacterial cell wall. A screen biased toward compounds containing zinc-binding groups (ZBG’s) including thiols, carboxylic acids, boronic acids, phosphonates and hydroxamates has delivered a number of micromolar inhibitors of DapE from Haemophilus influenzae, including the low micromolar inhibitor L-captopril (IC50 = 3.3 μM, Ki = 1.8 μM). In vitro antimicrobial activity was demonstrated for l-captopril against Escherichia coli

Synthesis of Substituted 2-Amino-Cyclobutanones

A series of weakly nucleophilic nitrogen derivatives including carbamates, amides, sulfonamides, and anilines were reacted with 1,2‐bis(trimethylsilyloxy)cyclobutene under acidic conditions to afford various substituted 2‐aminocyclobutanone derivatives 3a–i in modest to excellent yields

Inhibitors of Bacterial N-Succinyl-L,L-diaminopimelic Acid Desuccinylase (DapE) and Demonstration of In Vitro Antimicrobial Activity

The dapE-encoded N-succinyl-l,l-diaminopimelic acid desuccinylase (DapE) is a critical bacterial enzyme for the construction of the bacterial cell wall. A screen biased toward compounds containing zinc-binding groups (ZBG’s) including thiols, carboxylic acids, boronic acids, phosphonates and hydroxamates has delivered a number of micromolar inhibitors of DapE from Haemophilus influenzae, including the low micromolar inhibitor l-captopril (IC50 = 3.3 μM, Ki = 1.8 μM). In vitro antimicrobial activity was demonstrated for l-captopril against Escherichia coli