Bushy-Tailed Multicationic Quaternary Phosphonium Compounds: Potent Amphiphilic Disinfectants with Promising Therapeutic Indices.

Quaternary ammonium compounds (QACs) have been essential for protecting human health for almost a century, functioning as surface disinfectants and sanitizers. With bacterial resistance increasing against commercially available QACs, the development of novel antimicrobials with divergent architectures is essential for effective infection prevention and control. Toward this end, our group has expanded beyond traditional ammonium scaffolds and explored the development of quaternary phosphonium compounds (QPCs).

Bushy-Tailed QACs: The Development of Multicationic Quaternary Ammonium Compounds with a High Degree of Alkyl Chain Substitution.

Quaternary ammonium compounds have served as a first line of protection for human health as surface disinfectants and sanitizers for nearly a century. However, increasing levels of bacterial resistance have spurred the development of novel QAC architectures. In light of the observed reduction in eukaryotic cell toxicity when the alkyl chains on QACs are shorter in nature (≤10 C), we prepared 47 QAC architectures that bear multiple short alkyl chains appended to up to three cationic groups, thus rendering them "bushy-tailed" multiQACs.

Ni-Catalyzed Enantioselective Intramolecular Mizoroki-Heck Reaction for the Synthesis of Phenanthridinone Derivatives.

A Ni-catalyzed enantioselective intramolecular Mizoroki-Heck reaction has been developed to transform symmetrical 1,4-cyclohexadienes with attached aryl halides into phenanthridinone analogues containing quaternary stereocenters. Herein, we report important advances in reaction optimization enabling control of unwanted proto-dehalogenation and alkene reduction side products. Moreover, this approach provides direct access to six-membered ring heterocyclic systems bearing all-carbon quaternary stereocenters, which have been much more challenging to form enantioselectively with nickel-catalyzed Heck reactions.

Catalytic Enantioselective Birch-Heck Sequence for the Synthesis of Phenanthridinone Derivatives with an All-Carbon Quaternary Stereocenter.

Novel phenanthridinone analogues with an all-carbon quaternary stereocenter have been enantioselectively synthesized using the Birch-Heck sequence. Flat phenanthridinone structures have extensive bioactivity but consequently also suffer from poor therapeutic selectivity. The addition of a quaternary center to the phenanthridinone skeleton has the potential to generate more complex analogues with improved selectivity.