Lolamicin is an experimental antibiotic.^[1] It targets Gram-negative bacteria without significantly affecting typical gut microbes.^[2] Lolamicin was discovered by a team led by Paul Hergenrother at the University of Illinois Urbana-Champaign and was first reported in 2024.^[1]

In a mouse model of bacterial infection, lolamicin was found to be especially effective against Escherichia coli, Klebsiella pneumoniae, and Enterobacter cloacae.^[3]

Lolamicin works by interfering with the lipoprotein transport system of Gram-negative bacteria.^[1]

Lolamicin is synthesized in five steps. Initially, methyl 3-hydroxybenzoate undergoes nucleophilic substitution with 3-(chloromethyl)benzonitrile in the presence of potassium carbonate, forming the corresponding ether. The ester is then hydrolyzed under basic conditions to yield the carboxylic acid. In a two-step process, the carboxylic acid is activated using PyBOP and reacted with N,O-dimethyl hydroxylamine hydrochloride to form the corresponding methoxamide. This intermediate is then subjected to condensation with 2,4,6-collidine under low-temperature conditions using lithium diisopropylamide (LDA), yielding a dimethylpyridine derivative. Finally, treatment with hydrazine monohydrate under reflux promotes cyclization to produce the final pyridine-pyrazole core structure of lolamicin.^[1]