Total Synthesis of Phomopsene

Описание: This video is about the first total syntheses of polycyclic diterpene phomopsene, which has been achieved using a unique cascade reorganization of carbon-carbon single bonds. The method involves: A novel Nazarov cyclization/double ring expansion developed by the authors, enabling rapid and stereospecific construction of the 5/5/5/5 tetraquinane scaffold with contiguous quaternary centers; and a one-pot strategic ring expansion through Beckmann fragmentation/recombination to efficiently assemble the required 5/5/6/5 tetracyclic skeleton of the target molecules.
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Also in this video:
1,4-addition of the Grignard reagent and hydrolysis.
CDI-mediated amide coupling.
Formation of the cyclobutanone via enol triflate.
Horner−Wadsworth−Emmons reaction and hydrolysis.
Formation of the β-ketoester.
Condensation with cyclobutanone.
Nazarov 4π-conrotatory electrocyclization/double ring expansion.
Krapcho decarboxylation.
Allylic Rubottom-type oxidation.
Protection of the alcohol with MOMCl.
1,4-reduction with sodium borohydride.
Oximation with hydroxylamine.
Beckmann fragmentation.
DIBALH reduction of the nitrile.
Cyclization on a neutral alumina column.
Dess−Martin oxidation and double bond migration.
Stereoselective installation of the methyl group.
Removal of the MOM group under acidic conditions.
Hydrogenation of the enone, followed by Dess−Martin oxidation.
Selective protection of the carbonyl group on the six-membered ring.
Oxidation of the ketone to the corresponding enone.
1,4-addition, oxidation, and hydrogenation sequence.
Removal of the carbonyl group and deprotection.
Radical bromination and elimination.
Removal of the carbonyl group.
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Reference:
J. Am. Chem. Soc. 2023, 145, 21170−21175. https://doi.org/10.1021/jacs.3c07044