Scalable and Chromatography-Free Synthesis of Settlement Inhibition Glucosamine Derivative

A scalable synthesis (>10 g) of a glucosamine derivative with settlement inhibition activity against the barnacles of Amphibalanus amphitrite is described. We previously reported the importance of an isocyanide group for settlement inhibition activity. In this work, the isocyanide group was installed into a glucosamine derivative. The synthesis is chromatography-free throughout the entire synthetic scheme, enabling efficient and cost-effective preparation of the final product to provide a pure product with potent settlement inhibition activity (50% effective concentration = 0.30 µg/mL) along with low toxicity, 50% lethal concentration >10 µg/mL. Inexpensive reagents are also employed in the synthesis.