Total synthesis of ma'edamines E and F via Chichibabin pyridinium synthesis

Abstract

Marine sponges, particularly those in the order Verongiida, produce bromotyrosine-derived alkaloids with notable antimicrobial and cytotoxic activities. This study focuses on the synthesis of ma'edamines E and F, analogs of the previously isolated ma'edamine C from the sponge Suberea sp. The synthetic strategy is based on the Chichibabin pyridinium synthesis, in which substrate hydrophobicity and aqueous solubility significantly influenced reaction outcomes. Modulating substrate hydrophilicity enabled efficient synthesis of key intermediates en route to ma'edamines E and F. These findings offer insights into optimizing reaction conditions for the synthesis of complex pyridinium alkaloids with potential therapeutic applications.