Organic Chemistry

General Synthetic Entry to Dihydrooxepine-spiroisoxazoline Natural Products: Total Synthesis of Psammaplysin A

Authors

Abstract

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

Version notes

Correction of grammar mistakes and typos. Correction of structure 4 of Scheme 1.

Content

Thumbnail image of Psammaplysin A_ChemRxiv_2022_New.pdf

Supplementary material

Thumbnail image of SI_Psammaplysin A_ChemRxiv_2022_P1_Procedures.pdf
Supporting Information P1
Experimental procedures.
Thumbnail image of SI_Psammaplysin A_ChemRxiv_2022_P2_Xray.pdf
Supporting Information P2
Xray.
Thumbnail image of SI_Psammaplysin A_ChemRxiv_2022_P3_NMR.pdf
Supporting Information P3
NMR spectra.