Antifouling activity of synthetic γ-hydroxybutenolides

The desire to provide greener antifouling (AF) biocides for incorporation into marine paints has led to the discovery of many AF natural products. However, economical and sustainable supply of these natural products is often lacking. Twenty one structurally diverse γ-hydroxybutenolides - inspired by two natural AF sesterterpene γ-hydroxybutenolides (cavernosolide and lintenolide A) - were synthesized and tested for in vitro AF efficacy against the marine bryozoan larvae (Bugula neritina) and algae (Isochrysis galbana). The most potent analogues (EC50 ca. 2 μg/mL) had AF activity comparable to the natural products (EC50 ca. 0.6 μg/mL). Sites of attachment of side chains to the γ-hydroxybutenolide core structure had little effect on AF activity, however a clear relationship was established between lipophilicity and AF activity. Four analogues were chosen for field trials, incorporated into paints and deployed on panels in the marine environment. These analogues were chosen to reflect logistics of large scale synthesis and to provide representation of diverse structural motifs. Without any primary or co-biocides (except ZnO as a paint pigment), two analogues demonstrated a pronounced AF effect by resisting biofouling for over 18 weeks, compared to the ZnO control of between 7 and 10 weeks. Fine tuning of the structural motifs and/or the inclusion of co-biocides in paint formulations provide the potential to increase AF efficacy further.