Total Synthesis of the Dihydrooxepine-Spiroisoxazoline Natural Product Psammaplysin A.

We report a general synthetic entry to dihydrooxepine-spiroisoxazoline (DOSI) natural products that culminated in the first racemic total synthesis of psammaplysin A. For the synthesis of the unique spirocyclic fragment we employed a strategy that features two key transformations: (1) a diastereoselective Henry reaction/cyclization sequence to access the C7 hydroxylated isoxazoline scaffold in one step and (2) a regioselective Baeyer-Villiger ring expansion to install the fully substituted dihydrooxepine and avoid the risk of a previously observed oxepine-arene oxide rearrangement. The overall synthesis proceeds in 13 steps from an inexpensive starting material.

Total Synthesis of Oxepin and Dihydrooxepin Containing Natural Products.

The construction of oxepin and dihydrooxepin containing natural products represents a challenging task in total synthesis. In the last decades, a variety of synthetic methods have been reported for the installation of these structural motifs. Herein, we provide an overview of synthetic methods and strategies to construct these motifs in the context of natural product synthesis and highlight the key steps of each example.