Total Synthesis of the Dihydrooxepine-Spiroisoxazoline Natural Product Psammaplysin A
Jan Paciorek, Denis Höfler, Kevin Rafael Sokol, Klaus Wurst, Thomas Magauer
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.
Topics & Concepts
ChemistryRegioselectivityTotal synthesisNatural productRing (chemistry)StereochemistrySequence (biology)Combinatorial chemistryOrganic chemistryCatalysisBiochemistryChemical synthesis and alkaloidsSynthetic Organic Chemistry MethodsAsymmetric Synthesis and Catalysis