Total Synthesis of Mansonone F and its Derivatives via Regioselective C-H Alkylation.

Mansonone F, a significant natural antimicrobial agent, has been synthesized through a transition metal-mediated late-stage functionalization strategy that introduces alkyl groups at the C6 position. This approach enables the site-selective introduction of alkyl groups at the C6 position, significantly expanding the structural diversity of this pharmacologically relevant scaffold. The synthetic pathways were developed from two distinct precursors: 1-bromo-2-methylnaphthalene and 2-bromo-1-naphthol. Both routes efficiently constructed the characteristic pyrano-fused naphthoquinone core and introduced diverse C6-alkyl substituents with substantially improved yields compared to previously reported methods. The demonstrated versatility and efficiency of this synthetic strategy represent a notable advance in the chemical exploration of this promising class of bioactive naphthoquinone derivatives.