General diastereoselective synthetic approach toward isospongian diterpenes. Synthesis of (-)-marginatafuran, (-)-marginatone, and (-)-20-acetoxymarginatone.
This work describes a synthetic approach to the carbocyclic skeleton of isospongian diterpenes that uses the commercially available monoterpene (S)-carvone as a C-ring synthon, which is incorporated into the tetracyclic isospongian framework via a C→ABC→ABCD ring annulation strategy using intramolecular Diels-Alder and ring-closing metathesis reactions. This approach has been successfully used to prepare both the title natural isospongians and several nonnatural oxygenated analogues. A preliminary evaluation of the inhibitory activity of the small collection of synthesized isospongians on the mammalian mitochondrial respiratory chain revealed that most were able to inhibit the integrated electron transfer chain (NADH oxidase activity) in the micromolar range.
Departamento de Química Orgánica, Facultad de Química, Universidad de Valencia, Dr Moliner 50, 46100 Burjassot, Valencia, Spain.
Antonio
A
Gris
Nuria
N
Cabedo
Ismael
I
Navarro
Ignacio
I
de Alfonso
Consuelo
C
Agulló
Antonio
A
Abad-Somovilla
D004224:Diterpenes / Q000138:chemical synthesis* / Q000737:chemistry; D008968:Molecular Conformation; D013237:Stereoisomerism
C575956:20-acetoxymarginatone; D004224:Diterpenes; C575955:marginatone