New brominated sesquiterpenes from the red alga Laurencia hetroclada Harvey, and their immunosuppressive activity studies

Abstract

Red algae of the genus Laurencia Harvey (Ceramiales, Rhodomelaceae) is a complex genus, encompassing a large variety of morphologicallycomplex algal species. In continuation of our work on chemistry and biological activity studies of some Sri Lankan seaweeds, we examined the chemistry of MeOH extract of Laurencia hetroclada collected from Tangalle coast. Above extract was subjected to column chromatography followed by PTLC gave a new brominated sesquiterpene 1 along with two known compounds, algoane 2, and caulerpin 3. The 13C NMR spectrum along with the DEPT experiments of 1 revealed only 15 carbon signals corresponding to four methyls, five methylene, one methine and five quaternary carbons. The 1H NMR (CD3OD, 500 MHz) spectrum of 1 showed signals due to three methyls, four methylenes, and two methine protons. The singlets resonated at 1.25 (3H, s), 1.27 (3H, s), and 1.85 (3H, s) were assigned to Me-8’, Me-6’, and Me-9’, respectively. The characteristic downfield proton at 4.83 (dd, J = 4.2,15 Hz) was assigned to H-4, geminal to the Br atom, whereas the proton that resonated at 3.96 (d, J = 1.7 Hz) was assigned to the oxymethine H- 1. Furthermore, the olefinic singlet resonated at 5.26 was assigned to Ha-7’ and Hb-7. The down field carbon atoms resonated at 110.2 and 165.2 were assigned to olefinic carbon atoms. The positive CI MS of 1 showed the molecular ion peak [M+H]+ at m/z 349 along with isotopic peak at m/z 351 (1:1), indicating the presence of a Br atom in the molecule. The above MS data were found to be consistent with the molecular formula C15H25O4Br with 3 degrees of unsaturation. A comparison of the NMR spectroscopic data of 1 with those of 2 suggested a similar skeleton with differences in substitution pattern and unsaturation sites. From the above spectral data, the structure of 1 was confirmed as a new natural product 4-bromo-5-methyl-2-(3’-hydroxy-1’,3’- dimethyl-2’ methylenecyclopentyl) cyclohexane-1,2,5- triol. Caulerpin (3) showed a significant dose suppressive effect with an IC50 5.8 ± 1.0 μg/mL on Tcell proliferation assay.