2.1.3. Chagosensine

Chagosensine (**59**) (Figure 10), a chloro-substituted macrolide, was isolated from the calcareous sponge *Leucetta chagosensis*. Its structure, consisting of a sixteen-membered macrolide, two 2,5-*trans*-disubstituted tetrahydrofuran rings embedded within, a unique *Z,Z*-configured chloro-1,3-diene unit, and eleven chiral centers, was assigned by spectroscopic techniques and degradation experiments [47]. Chagosensine structure is similar to the haterumalide and biselide families, but the conjugated chlorodiene unit is only present in this natural product. Nevertheless, Fürstner and co-workers have shown disagreement with the proposed structure and have carried out different synthetic studies in order to demonstrate their arguments [48,49].

**Figure 10.** Initially proposed structure of chagosensine.

The synthesis of putative chagosensine proposed by Fürstner relied on Mukaiyama cyclizations using Co(II) catalyst to obtain 2,5-*trans*-tetrahydrofuran derivatives **60** and **61**

from the appropriate alkenols **62** and **63** [48]. After further elaboration, optimized Stille coupling of 1,2-bisstannane derivative **64** and vinyl iodide **65** provided the precursor diene **66** in moderate yield. Finally, six additional steps, including a Yamaguchi lactonization, produced the desired macrocycle (Scheme 11). The product proved unstable and had to be transformed into the known methyl esther, though huge deviations in the NMR seemed to indicate that the structure was misassigned. More recently, further efforts were made to access eight different diastereomers in order to find the correct structure [49]. Unfortunately, none of the structures synthesized matched the original spectroscopic data. Thus, the structure of this intriguing marine macrolide remains unresolved.

**Scheme 11.** Synthesis of putative chagosensine.
