New Terpenoids from the Brown AlgaStypopodiumzonale

Enrique Dorta, Mercedes Cueto, Inmaculada Brito, José Darias
2002 Journal of natural products  
Three new terpenoids, 1a-3a, and the known metabolites atomaric acid, stypoquinonic acid, and 5′adesmethyl-5′-acetylatomaric acid have been isolated from the tropical brown alga Stypopodium zonale. The structures and relative stereochemistry of the methyl ester of 1a-3a were determined by spectral methods. The methyl ester of 3a exhibits in vitro cytotoxic activity against human lung and colon carcinoma. Brown algae possess the ability to produce a great variety of secondary metabolites with
more » ... metabolites with very different skeleton types and functionalities. 1 Among this group the brown algae Taonia atomaria, Stypopodium flabelliforme, and Stypopodium zonale are known to produce a unique series of cyclic terpenes of mixed biogenesis, such as taondiol and atomaric acid isolated from T. atomaria. 2, 3 Taondiol was also isolated from S. zonale as the enantiomer of that which occurs in T. atomaria. 4 Diterpenoids isolated from S. flabelliforme show insecticidal activity. 5 S. zonale was found to excrete rust-colored substances that proved to be ichthyotoxic, 6 and many of the compounds isolated from this alga have been found to have ichthyotoxic activity. Crude extracts of S. zonale showed weak antimicrobial activity. 4,7 Stypoldione is a potent inhibitor of synchronous cell division in a fertilized sea urchin egg assay 4 and an inhibitor of microtubulin polymerization. 8 Stypoquinonic acid and atomaric acid showed inhibition of tyrosine kinase (p56 lck ) and weak antibacterial activity. 9 In this paper we report on the isolation and structure determination of the methyl esters, 1-3, and of three new acids, 1a-3a, that were isolated together with atomaric acid, 3,9 stypoquinonic acid, 9 and 5′a-desmethyl-5′-acetylatomaric acid 10 from Stypopodium zonale (L.) Lamouroux (Dyctiotaceae) collected in the Macaronesia Archipelago. Compound 3 exhibits in vitro cytotoxic activity against human colon carcinoma cell lines HT-29 (IC 50 <2.5 µg/mL) and H-116 (IC 50 2.5 µg/mL) and human lung carcinoma A-549 (IC 50 2.5 µg/mL). Compounds 1a-3a were isolated as a mixture, homogeneous by TLC, from a fraction of the crude extract (see Experimental Section). The compounds were separated as their methyl ester derivatives, 1-3, by recycling-HPLC after methylation of the mixtures of the acids. The MS and 1 H and 13 C NMR spectroscopic data of compounds 1-3 suggested that they are closely related to atomaric acid. Compound 1 was isolated as a yellow oil. The EIMS spectrum showed a peak at m/z 430 that corresponds to the molecular formula C 26 H 38 O 5 [M] + (HRMS). An absorbance for a hydroxyl group, a carboxyl group, and a carbonyl group were observed at 3467, 1737, and 1707 cm -1 , respectively, in the IR spectrum. The 13 C NMR spectrum (Table 1) displayed signals for a ketone at δ 211.8, a methyl ester group at δ 174.3, and six olefinic carbons (two methines and four quaternary carbons) that confirmed the presence of an aromatic ring in compound 1. The 1 H NMR spectrum showed signals for two meta-coupled aromatic protons at δ 6.55 (d, J ) 2.9) and 6.70 (d, J ) 2.9), a broad peak at δ 4.30 assigned to the phenolic proton, one methoxy group at δ 3.73 (s, 3H), one methyl ester group at δ 3.66 (s, 3H), a benzylic methylene at δ 3.03 (d, J ) 13.8) and 2.36 (d, J ) 13.8), and an aromatic methyl group at δ 2.23 (s, 3H). In the upfield region appear signals for three methyl groups at δ 1.21 (3H, d, J ) 6.9), 0.91 (3H, s), and 0.80 (3H, s). Compound 1 has three carbons less than atomaric acid. Comparison of the spectroscopic data of 1 with those of atomaric acid indicates that there is a ketone at C-10 in compound 1 instead of the isopropylene group of atomaric acid. This information was confirmed by HMBC correlations of protons H-8, H-9, and H-11 with C-10 at δ 211.8 and also by the MS peaks at m/z 152 and 279, corresponding to fragments A and B (Figure 1 ), respectively. Compound 2 was isolated as a yellow oil. The EIMS spectrum showed a peak at m/z 416, which corresponds to the molecular formula C 25 H 36 O 5 [M] + (HRMS). Its 1 H and 13 C NMR spectra are very close to those of compound 1 (Table 1) , the most significant difference being the presence, for compound 2, of a phenolic signal at
doi:10.1021/np020090g pmid:12444716 fatcat:j7imorazbzb3tezh5pbsopwgfq