Effective Synthesis and Antifouling Activity of Dolastatin 16 Derivatives

Some derivatives of dolastatin 16, a depsipeptide natural product first obtained from the sea hare Dolabella auricularia, were synthesized through second-generation synthesis of two unusual amino acids, dolaphenvaline and dolamethylleuine. The second-generation synthesis enabled derivatizations such as functionalization of the aromatic ring in dolaphenvaline. The derivatives of fragments and whole structures were evaluated for antifouling activity against the cypris larvae of Amphibalanus amphitrite. Small fragments inhibited the settlement of the cypris larvae at potent to moderate concentrations (EC50 = 0.60-4.62 mu g/mL), although dolastatin 16 with a substituent on the aromatic ring (24) was much less potent than dolastatin 16.

Automated summary

This study successfully synthesized some derivatives of dolastatin 16 through second-generation synthesis and evaluated their antifouling activity. The results showed that certain small fragments exhibited potent inhibitory activity against the settlement of cypris larvae.