Rearrangement-based total syntheses of oxacyclic natural products

International audienceOxacycles are commonly found in natural products. Some compounds of interest to us, due to their complexity and biological properties, are based on the seven-membered oxepane or oxepin motif, like the fungal cyclotripeptides janoxepin and varioxepin A, or the plant 2,5-dihydrobenzoxepin radulanin A. Numerous strategies have been described in the literature for their synthesis through C-C (e.g. metathesis) or C-O (e.g. Mitsunobu reaction) bond formation. However, these strategies use long synthetic sequences to reach the precursors. In this poster, we want to disclose our latest results on the synthesis of oxacycles. Several rearrangement-based methodologies will be described. First, the retro-Claisen [3,3] rearrangement of cis-2-vinylcyclopropane carboxaldehydes allowed us to synthesize two different natural products using a fragment-based strategy: janoxepin1 and radulanin A.2 Second, an interrupted Hock cleavage of 1-hydroperoxycycloalkanes led to new oxacycles and allowed us to synthesize substituted benzoxepanes and chromanes like the natural product erythrococcamide B. In addition, a photochemical rearrangement should complete this panel of methodologies.Our total synthesis of janoxepin, including a strong methodological development for each key step, uses a fragment-based strategy leading to an important increase of complexity through the retro-Claisen rearrangement. The completion of the synthesis was particularly challenging, when it came to oxidize the dihydrooxepin intermediate into the oxepin ring. Our total synthesis of radulanine A employed a similar rearrangement but here, the challenge lied on the aromatization step. Overall, these works show that the retro-Claisen rearrangement can be useful in total synthesis