Isocyanides Derived from α,α‐Disubstituted Amino Acids: Synthesis and Antifouling Activity Assessment

Herein, we contribute to the development of environmentally friendly antifoulants by synthesizing eighteen isocyanides derived from α,α‐disubstituted amino acids and evaluating their antifouling activity/toxicity against the cypris larvae of the Balanus amphitrite barnacle. Almost all isocyanides showed good antifouling activity without significant toxicity and exhibited EC₅₀ values of 0.07 – 7.30 μg/mL after 120‐h exposure. The lowest EC₅₀ values were observed for valine‐, methionine‐, and phenylalanine‐derived isocyanides, which achieved > 95% cypris larvae settlement inhibition at concentrations of less than 30 μg/mL without exhibiting significant toxicity. Thus, the prepared isocyanides should be useful for further research focused on the development of environmentally friendly antifouling agents.