Polyhalogenated Indoles from the Red Alga Rhodophyllis membranacea: The First Isolation of Bromo-Chloro-Iodo Secondary Metabolites

Abstract

An unusual tetrahalogenated indole with the exceptionally rare inclusion of the three halogens bromine, chlorine, and iodine was found using mass spectrometry within a fraction of a semipurified extract obtained from the red alga Rhodophyllis membranacea. We report herein the isolation and structure elucidation, using a combination of NMR spectroscopy and mass spectrometry, of 11 new tetrahalogenated indoles (1-11), including four bromochloroiodoindoles (5-7, 10). Several were evaluated for cytotoxic and antifungal activities against the HL-60 promyelocytic cell line and Saccharomyces cerevisiae, respectively.

Iodinated Meroditerpenes from a Red Alga Callophycus sp.

“…Distinct chemical shift ranges were observed for halogenated carbons of 3–5 : either δ C 112–114 or 82–89, which correspond to brominated or iodinated aromatic carbons, respectively. 15 The same strategy used to characterize the aromatic ring of 2 was followed; namely, determination of C-2′ and C-4′ from HMBC correlation with H 2 -1 and determination of the halogens substitution pattern on C-1′ and C-5′ with the help of HMBC correlations from H-2′. The observation of a 4 J HMBC correlation between H-2′ and C-5′ seemed initially problematic, but this correlation was considerably weaker than 2 J H32′,C31′ (Figure 4).…”

“…13,14 Recently, bromo-chloro-iodoindoles from the red alga Rhodophyllis membranacea were reported as the first natural products containing three halogen types. 15 Also, five terpenes iodinated at a terminal methylene or on a benzene ring have been described from red algae. 16–18 Herein, we report the isolation and structural characterization of five new iodinated (and brominated) meroditerpenes ( 1–5 ), along with the determination of their absolute stereochemistries by quantitative NOESY, ECD spectroscopy, and DFT modeling.…”

Marine natural products

“…371 Halogenated indoles are another commonly encountered structural type, with eleven polyhalogenated indoles 772-782 from Rhodophyllis membranacea, including six which were the rst isolation of bromo-chloro-iodo secondary metabolites, as exemplied by 776. 372 Further related compounds were four brominated indole related alkaloids 783-786 (Laurencia similis), 373 and bromophenol 787 (Odonthalia corymbifera). 374 Papers describing work on new bioactivities for known compounds from red algae include the reporting of the larvicidal potential of obtusol (Laurencia dendroidea) 375 against the dengue fever mosquito Aedes aegypti, 376 bis(2,3-dibromo-4,5dihydroxybenzyl) ether (BDDE) (Odonthalia corymbifera) 377 as a novel PTP1B inhibitor and potential anti-diabetic agent, 378 immunomodulatory effects of the mycosporine-like amino acids shinorine and porphyra-334 from Porphyra sp., 379 and the insecticidal activity guided isolation of palytoxin 380 from Chondria armata.…”

Costatone C—A new halogenated monoterpene from the New Zealand red alga plocamium angustum

“…The absolute configuration of costatone A was solved by X-ray crystallography, and has since been isolated from samples identified as P. angustum [4]. As part of our investigation into the secondary metabolites of common Rhodophytes collected from the coast of Wellington, New Zealand [12], it was observed using 1 H NMR spectroscopy that an extract of an alga identified as "P. angustum" had many chemical shifts indicative of halogenated monoterpenes. A detailed analysis of the alga resulted in the isolation of the two major compounds that have not been previously reported from "P. angustum", new compound 7 and known compound 8 (Scheme 1).…”