Stationary and slow-moving marine organisms regularly employ a
natural product chemical defense to prevent being colonized by marine
micro- and macroorganisms. While these natural antifoulants can be
structurally diverse, they often display highly conserved chemistries
and physicochemical properties, suggesting a natural marine antifouling
pharmacophore. In our current report, we investigate the marine natural
product phidianidine A, which displays several chemical properties
found in highly potent marine antifoulants. Phidianidine A and synthetic
analogues were screened against the settlement and metamorphosis of Amphibalanus improvisus cyprids, and several of the compounds
displayed inhibitory activities at low micromolar concentrations with
IC50 values down to 0.7 μg/mL observed. The settlement
study highlights that phidianidine A is a potent natural antifoulant
and that the scaffold can be tuned to generate simpler and improved
synthetic analogues. The bioactivity is closely linked to the size
of the compound and to its basicity. The study also illustrates that
active analogues can be prepared in the absence of the natural constrained
1,2,4-oxadiazole ring. A synthetic lead analogue of phidianidine A
was incorporated in a coating and included in antifouling field trials,
where it was shown that the coating induced potent inhibition of marine
bacteria and microalgae settlement.
An efficient method for the synthesis of the carbazole scaffold was designed and investigated. The method was developed to produce substituted carbazoles by an intramolecular combination of a free amine group and an arene. The steps of the method involved tandem Pd‐catalyzed C–H activation and intramolecular C–N bond formation. The method showed good functional group tolerance, and substituent(s) could be on either of the two rings or on both of the two rings of the 2‐aminobiphenyl substrate. After ring closure, the reduced Pd catalyst was oxidized to PdII by hydrogen peroxide. The novel method was also demonstrated to operate excellently with the corresponding 2‐N‐acetylaminobiphenyls.
A simple and efficient method for Suzuki cross‐coupling of highly substituted and congested 1‐chloro‐2‐nitrobenzene with phenylboronic acid was developed, investigated, and optimized. The reaction conditions comprises a mixture of MeOH and water (4:1) as the reaction medium, readily available and cheap Pd(PPh3)4 as catalyst, sodium carbonate as base, and microwave heating, which affords a fast reaction rate with good outcomes. The procedure was proven to have high functional group tolerance with phenylboronic acid and for 1‐chloro‐2‐nitrobenzene and thus is a general method for the synthesis of 2‐nitrobiphenyl. The target scaffold, 2‐nitrobiphenyls, was produced in excellent yields with excellent selectivities in all cases.
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