3.4.2. Omaezakianol

Omaezakianol (**69**) (Figure 16) is a squalene-derived triterpene polyether that was isolated in 2008 from the red alga *Laurencia omaezakiana* by Morimoto and coworkers [64]. The same group rapidly reported its first asymmetric total synthesis and, therefore, stablished its absolute configuration [65]. Key steps were olefin cross-metathesis and an epoxide-opening cascade.

**Figure 16.** Structure of (+)-omaezakianol (**69**).

In 2010, Corey reported a short total synthesis via a biomimetic epoxide-initiated cationic cascade reaction [66]. Compound **70** was treated with camphorsulfonic acid (CSA) to induce the epoxide-opening cascade cyclization, producing **71**. Reduction of **71,** with sodium in acetone under reflux, formed the terminal double bond with opening of the THF ring, affording **69** in 76% yield (Scheme 10). Thus, the synthesis was accomplished in just six steps from squalene.

**Scheme 10.** Synthesis of (+)-omaezakianol **69** by Corey via an epoxide-initiated cationic cascade.

Another biomimetic epoxide-opening cascade for the synthesis of **(+)-69** was reported in 2013 by Morimoto and coworkers [67]. The cascade, which mimics the direct hydrolysis mechanism of epoxide hydrolases, begins with 5-*exo* cyclization of the terminal epoxide triggered by Brønsted acid catalysis. Intermediate **72** then undergoes an epoxide-opening cascade reaction with TfOH to afford **(+)-69** in 33% yield (Scheme 11).

**Scheme 11.** Synthesis of (+)-omaezakianol (**(+)-69**) by a biomimetic epoxide-opening cascade.
