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Total Synthesis of Ganoapplanin Enabled by a Radical Addition/Aldol Reaction Cascade.

ABSTRACT: The total synthesis of the Ganoderma meroterpenoid ganoapplanin, an inhibitor of T-type voltage-gated calcium channels, is reported. Our synthetic approach is based on the convergent coupling of a readily available aromatic polyketide scaffold with a bicyclic terpenoid fragment. The three contiguous stereocenters of the terpenoid fragment, two of which are quaternary, were constructed by a diastereoselective, titanium-mediated iodolactonization. For the fusion of the two fragments and to simultaneously install the crucial biaryl bond, we devised a highly effective two-component coupling strategy. This event involves an intramolecular 6-exo-trig radical addition of a quinone monoacetal followed by an intermolecular aldol reaction. A strategic late-stage oxidation sequence allowed the selective installation of the remaining oxygen functionalities and the introduction of the characteristic spiro bisacetal structure of ganoapplanin.

SUBMITTER: Muller N

PROVIDER: S-EPMC7616391 | biostudies-literature | 2024 Aug

REPOSITORIES: biostudies-literature

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Total Synthesis of Ganoapplanin Enabled by a Radical Addition/Aldol Reaction Cascade.

Müller Nicolas N Kováč Ondřej O Rode Alexander A Atzl Daniel D Magauer Thomas T

Journal of the American Chemical Society 20240807 33

The total synthesis of the <i>Ganoderma</i> meroterpenoid ganoapplanin, an inhibitor of T-type voltage-gated calcium channels, is reported. Our synthetic approach is based on the convergent coupling of a readily available aromatic polyketide scaffold with a bicyclic terpenoid fragment. The three contiguous stereocenters of the terpenoid fragment, two of which are quaternary, were constructed by a diastereoselective, titanium-mediated iodolactonization. For the fusion of the two fragments and to ...[more]

PMID: 39110664

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