3.4.1. Intricatetraol

Intricatetraol (**64**) is a halogenated triterpenoid with a *C2* symmetry that was isolated in 1993 from the red alga *Laurencia intricata* (Figure 15). Suzuki and coworkers observed that a crude fraction of the extract showed cytotoxic activity against P388 leukemia cells with an IC50 value of 12.5 μg/mL. Nevertheless, pure intricatetraol was no longer active after chromatography. At first, its stereostructure was proposed as being based on its hypothetical biogenesis [61]. In 2006, Morimoto confirmed this assignment by synthesizing a degradation product of intricatetraol through a two-directional synthesis [62].

**Figure 15.** Structure of (+)-intricatetraol **64**.

One year later, Morimoto completed the asymmetric total synthesis of **(+)-64** and, thus, determined its absolute configuration [63]. The tetrahydrofuran ring **65** was stereospecifically constructed by treatment of diepoxyalcohol **66** with lithium hydroxide aqueous solution. A further 10 steps (with an accumulated yield of 30%) were needed to obtain intermediate **67**, which was then dimerized to afford **68** by olefin metathesis with a secondgeneration Grubbs catalyst. Final diimide reduction of intermediate **68** produced **(+)-64** (Scheme 9).

**Scheme 9.** Synthesis of (+)-intricatetraol (**(+)-64**).
