Polycyclic ether natural products have attracted considerable attention for their toxicological properties, their structural complexity, and their potential use as therapeutic agents. Our current research focuses on constructing fused polycyclic ethers through diastereoselective exo-mode oxacyclizations, with stereo induction in the ring-closing step from an allylic oxygen substituent. This presentation will detail our investigation of the vinyloxirane substrate (1), which undergoes Brønsted acid-catalyzed cycloisomerization to form the trans-fused cyclic ether (2). The product structure corresponds to the trans-syn-trans substructure (3) found in a variety of polycyclic ether natural products, ranging from brevenal to yessotoxin and maitotoxin. Our presentation will also describe convergent and stereoselective syntheses of substrates including compound (1), our tests of mechanistic hypotheses regarding the diastereoselectivity of the formation of cycloisomerization product (2), and ongoing work to establish the generality and scope of this method with other ring sizes and substituent patterns.

Stereoselective synthesis of fused polycyclic ethers: Exo-mode oxacyclizations of vinyloxiranes

251st National Meeting (2016)

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.