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

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.

SUBMITTER: Paciorek J

PROVIDER: S-EPMC9634798 | biostudies-literature | 2022 Nov

REPOSITORIES: biostudies-literature

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

Paciorek Jan J Höfler Denis D Sokol Kevin Rafael KR Wurst Klaus K Magauer Thomas T

Journal of the American Chemical Society 20221021 43

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 dihyd ...[more]

PMID: 36270001

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