3.4.3. Longilenes

Longilenes are triterpene polyethers that were first isolated from the wood of *Eurycoma longifolia* in the form of (−)-longilene peroxide (**(***−***)-73**) [68,69]. In 2001, Morimoto accomplished its total synthesis [70] and determined its absolute configuration. The same author also developed a biomimetic synthesis of the C9–C16 fragment of oxasqualenoids in an enantioselective manner [71]. This chiral building block could be used as an advanced intermediate for the synthesis of different polyethers, such as teurilene, longilene peroxide, or glabrescol.

In 2018, Fernández and Daranas reported the isolation of other members of the family, namely (+)-longilene peroxide (**(+)-73**), longilene (**74**), and the derivative (+)-prelongilene (**(+)-75**), from the red seaweed *Laurencia viridis* [72]. These compounds present Ser/Thr protein phosphatase 2A inhibitory activity (Figure 17). To date, no synthetic approaches have been reported.

**Figure 17.** Structure of (−)-longilene peroxide (**(***−***)-73**), (+)-longilene peroxide (**(+)-73**), longilene (**74**), and the derivative (+)-prelongilene (**(+)-75**).

3.4.4. Laurokanols and Yucatecone

In 2021, laurokanols A–E (**76–80**) and yucatecone (**81**) (Figure 18), polyether triterpenes, were isolated from the red alga *Laurencia viridis* [73]. Laurokanols have an unprecedented tricyclic core with an [6,6]-spiroketal system. Yucatecone is the first compound of this series with an *R* configuration at the C14 position. A biogenetic model, supported by DFT calculations, was then postulated for the biogenesis of yucatecone.

**Figure 18.** Structures of laurokanols A–E (**76**–**80**) and yucatecone (**81**).

3.4.5. Thyrsenol

Thyrsenol A (**82**) and B (**83**) (Figure 19) are polyether squalene derivatives that were isolated by Norte and coworkers in 1997 from the red alga *Laurencia viridis* [74]. Although both compounds show high activity against murine lymphoid neoplasm P-388 cells, compound **83** induced significantly higher inhibitory effects [75]. Other related compounds, such as thyrsiferol derivatives and dehydrovenustatriol, were found to be even more active. Therefore, it was postulated that the presence of a flexible chain around C14 to C19, and its configuration, are of particular importance for the bioactivity of these compounds. Later, Fernández and coworkers also found **83** to have protein phosphatase PP2A inhibitory activity [76]. The activity was comparable to that of dehydrothyrsiferol and thysiferyl-23-acetate, concluding that a hydroxyl group at C15 or C16 is a key factor for their intrinsic activity. In 2011, the isolation of other derivatives has been reported [77].

**Figure 19.** Structure of thyrsenol A (**82**) and B (**83**).
