The red seaweed Laurencia viridis is a rich source of oxygenated secondary metabolites that were derived from squalene. In study three novel compounds, (+)-longilene peroxide (1), longilene (2), and (+)-prelongilene (3) were isolated from this alga.

Squalene-derived polyethers belonging to the thyrsiferol and venustatriol series have shown different biological activities, such as cytotoxicity, integrin antagonist activity, and protein phosphate type 2A inhibition.

New bioactive molecules from marine sources, were isolated and the structural elucidation of three new marine polyether natural products, (+)-longilene peroxide (1), longilene (2), and (+)-prelongilene (3), and another two compounds (4–5), which were derived from the rapid degradation of 2 and 3.

The molecular formula of (+)-longilene peroxide (1) C30H52O8Na, was established by HRESIMS analysis, where its sodiated molecular ion was observed at m/z 563.3571. the marine polyether that was isolated from Laurencia viridis must be the enantiomeric form of the terrestrial (−)-longilene peroxide (6).

The HRESIMS analysis of the very unstable metabolite longilene (2) provided the molecular formula C30H52O7 that was based on the m/z 524.3716 (calculated for 524.3713 [M]+), as observed.

The resemblance of the NMR data in compound 1 and 2 suggested that the relative configurations of the stereocentres in 2 match those that were previously described for (+)-longilene peroxide (1) in accordance with a C2 symmetry.

Compound 3, (+)-prelongilene, was obtained as an amorphous white solid. Its molecular formula was established by ESI-HRMS as C30H52O6 (m/z 531.3655; calculated for 531.3662.

According to the simulation results, the binding modes of 1 and 3 to PP2A were very similar, as expected from their minor structural differences. However, the resulting (+)-longilene peroxide (1)-PP2A complex showed favorable contacts that were not observed in the (+)-prelongilene (3)-PP2A complex.

Among these, were the key hydrogen bonds that were formed between the hydroperoxide group with the Arg-214 and His-241 residues, as well as that between the hydroxyl group on C-23 and the Ile-123 residue.

On the other hand, from the analysis of the structure of the (+)-prelongilene-PP2A complex, no important favorable contributions were identified, but small unfavorable contacts with Trp-200, Hys-118, and Leu-243 were observed.

The overall orientation of the two ligands within the active site of PP2A was therefore very similar and the structural difference between these two molecules is the additional allylic hydroperoxide group at C-2 in 1.

For these reasons, it seems clear that the two predicted hydrogen bonds in the (+)-longilene peroxide (1)—PP2A complex are the factor leading to their differences in bioactivity. Three new squalene derived metabolites have been isolated from the red algae Laurencia viridis and their structures were determined by spectroscopic analysis.

Subsequently, the protein phosphatase type 2A inhibitory activity of the less labile compounds (1 and 3) was tested, resulting in 1 as a moderately active compound (IC50 11.3 μM), while the very similar compound 3 was completely inactive up to a concentration of 100 μM.