title: Geminal dialkyl derivatives of N-substituted pantothenamides: synthesis and antibacterial activity.
abstract: As a key precursor of coenzyme A (CoA) biosynthesis, pantothenic acid has proven to be a useful backbone to elaborate probes of this biosynthetic pathway, study CoA-utilizing systems, and design molecules with antimicrobial activity. The increasing prevalence of bacterial strains resistant to one or more antibiotics has prompted a renewed interest for molecules with a novel mode of antibacterial action such as N-substituted pantothenamides. Although numerous derivatives have been reported, most are varied at the terminal N-substituent, and fewer at the β-alanine moiety. Modifications at the pantoyl portion are limited to the addition of an ω-methyl group. We report a synthetic route to N-substituted pantothenamides with various alkyl substituents replacing the geminal dimethyl groups. Our methodology is also applicable to the synthesis of pantothenic acid, pantetheine and CoA derivatives. Here a small library of new N-substituted pantothenamides was synthesized. Most of these compounds display antibacterial activity against sensitive and resistant Staphylococcus aureus. Interestingly, replacement of the ProR methyl with an allyl group yielded a new N-substituted pantothenamide which is amongst the most potent reported so far.
authors: Department of Chemistry, McGill University, Montréal, Québec, Canada.
authors: T Olukayode
authors: TO
authors: Akinnusi
authors: Kenward
authors: K
authors: Vong
authors: Karine
authors: K
authors: Auclair
mesh_terms: D000577:Amides; D000900:Anti-Bacterial Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D055624:Methicillin-Resistant Staphylococcus aureus / Q000187:drug effects; D008722:Methods; D010205:Pantothenic Acid / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D054852:Small Molecule Libraries / Q000138:chemical synthesis; D013211:Staphylococcus aureus / Q000187:drug effects*; D013329:Structure-Activity Relationship
chemical_list: D000577:Amides; D000900:Anti-Bacterial Agents; D054852:Small Molecule Libraries; D010205:Pantothenic Acid