Advancements in Nitrogen Deletion Enabled Squalene Synthesis

Abstract

Squalene is a biologically active terpene and vaccine additive critical in the fight against influenza and SARS-COV-2. While squalene is typically purified from shark liver oil, plant-derived molecules are abundant, and recent advances in synthetic methodology show potential for cost-effective conversion of these compounds to squalene. Employing starting material of botanical origin, a nitrogen deletion enabled reaction sequence is reported that can deliver pure squalene in three steps under mild, scalable conditions. Preliminary experiments harnessing iridium-based photocatalysis for nitrogen extrusion were also performed to improve the sequence’s atom economy. If implemented in industry, this sequence has the potential to steer vaccine manufacturers away from animal-derived squalene sources, which often carry higher levels of marine-associated impurities that compromise vaccine reliability.