Synthesis and Antifouling Activity Evaluation of Analogs of Bromosphaerol, a Brominated Diterpene Isolated from the Red Alga Sphaerococcus coronopifolius

Abstract

Marine biofouling is an epibiotic biological process that affects almost any kind of submerged surface, causing globally significant economic problems mainly for the shipping industry and aquaculture companies, and its prevention so far has been associated with adverse environmental effects for non-target organisms. Previously, we have identified bromosphaerol (1), a brominated diterpene isolated from the red alga Sphaerococcus coronopifolius, as a promising agent with significant antifouling activity, exerting strong anti-settlement activity against larvae of Amphibalanus (Balanus) amphitrite and very low toxicity. The significant antifouling activity and low toxicity of bromosphaerol (1) motivated us to explore its chemistry, aiming to optimize its antifouling potential through the preparation of a number of analogs. Following different synthetic routes, we successfully synthesized 15 structural analogs (2–16) of bromosphaerol (1), decorated with different functional groups. The anti-settlement activity (EC50) and the degree of toxicity (LC50) of the bromosphaerol derivatives were evaluated using cyprids and nauplii of the cirriped crustacean A. amphitrite as a model organism. Derivatives 2, 4, and 6–16 showed diverse levels of antifouling activity. Among them, compounds 9 and 13 can be considered as well-performing antifoulants, exerting their activity through a non-toxic mechanism.

Antioxidant and Antimicrobial Properties of Selected Red Seaweeds from Central Portugal

“…A previous study reported the noteworthy antimicrobial activity of S. coronopifolius compared to a range of selected seaweed species, whose range of extracts with different solvents (n-hexane, dichloromethane and methanol) inhibit the growth of S. cerevisiae, while only the n-hexane extract inhibits the growth of B. subtilis and, similarly to our study, showed no inhibition against E. coli [39]. Terpenes, commonly found in brown algae, but less so in red algae, have been isolated from S. coronopifolius and targeted in several studies evaluating their potential as anti-cancer [51,[83][84][85][86], antibiotic [87] and anti-fouling [88][89][90] agents. The variations found in the present study are probably explained by the different extraction method, where only aqueous extracts were tested.…”

Fully Aqueous and Air-Compatible Cross-Coupling of Primary Alkyl Halides with Aryl Boronic Species: A Possible and Facile Method

“…The natural marine product, bromosphaerol ( 5a ), produced by the red alga Sphaerococcus coronopifolius, is shown to have marine antifouling activity. Semisynthetic generation of analogues to explore their function and tune their activity has been explored successfully; however, this requires a very selective and mild chemistry on the native molecule, which is inherently prone to substitution, elimination, and rearrangement reactions. By using the primary alkyl bromide as an orthogonal handle, we have been able to selectively install aryl groups to generate analogues 5b , a primary amine tag to enable LC–MS visualization, and 5c , a fluorescent tag, in 100% water on an analytical scale (Figure a).…”

New Insights on Biological Activities, Chemical Compositions, and Classifications of Marine Actinomycetes Antifouling Agents

“…The bromosphaerol, sphaerococcenol A, and bromotetrasphaerol derived from Sphaerococcus coronopifolius are effective anti-macrofouling agents against Balanus amphitrite larvae colonization [90]. Both Bromosphaerol and bromohydrin derivatives attain impressive safety profiles with an LC50/EC50 ratio of 434 (EC50 score of 0.23 mg/L and LC50 score > 100 mg/L) [91].…”