Total Synthesis of (±)-Welwitindolinone A Isonitrile

Keywords

(±)-welwitindolinone A isonitrile - oxindole alkaloids - Grignard addition - [2+2] cycloaddition - carbonylative cross-coupling - semipinacol rearrangement

Significance

Wood and co-workers report the total synthesis of (±)-welwitindolinone A isonitrile. The natural product, isolated from a blue-green algae in 1994, is characterized by a highly functionalized spirocyclobutane oxindole carbocyclic skeleton. Additionally, the target bears a densely packed and diverse array of functional groups.

 

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Comment

The synthesis commenced with the preparation of carbamate E from acetonide A (previously reported in Angew. Chem. Int. Ed. 2004, 43, 1270). After elaboration of E into allylic alcohol G, semi-pinacol rearrangement was induced with aqueous NaOCl, setting the quaternary stereocenter α to the chlorine in ketone H. Finally, formamide J was dehydrated and converted into putative isocyanate which, upon exposure to base, cyclized to the oxindole delivering (±)-welwitindolinone A isonitrile.

 

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Publikationsverlauf

Artikel online veröffentlicht:
22. Mai 2025