Total Synthesis of the Dihydrooxepine-Spiroisoxazoline Natural Product Psammaplysin A

J Am Chem Soc. 2022 Nov 2;144(43):19704-19708. doi: 10.1021/jacs.2c10010. Epub 2022 Oct 21.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Biological Products*
  • Cyclization
  • Spiro Compounds*
  • Stereoisomerism

Substances

  • psammaplysin A
  • Biological Products
  • Spiro Compounds