Total Synthesis of (±)-Leonuketal

Abstract

Cleavage of a C–C bond is a diversifying process in the biogenesis of <i>seco</i>-terpenoids that has produced fascinating molecular structures. Leonuketal is an 8,9-<i>seco</i>-labdane terpenoid with a unique tetracyclic structure, owing to a C–C bond cleavage event in its biosynthesis. We report the first total synthesis of leonuketal, featuring an unusual Shapiro-type reaction as part of an enabling auxiliary ring strategy, and a novel Au-catalysed spirocyclization of a b-keto(enol)lactone.

Total Synthesis of (±)-Leonuketal

“…In summary, we report the first total synthesis of complex seco -labdane leonuketal ( 1 ) over 23 steps from 12 . Successful completion of the synthesis was enabled by development of three key transformations: the Ti­(III)-mediated cyclization of 12 , the unusual Shapiro-type fragmentation of 11 as part of an auxiliary ring strategy, and the previously undescribed Au-catalyzed spirocyclization of a β-keto­(enol)­lactone ( 7 ) .…”

“…11 In summary, we report the first total synthesis of complex seco-labdane leonuketal (1) over 23 steps from 12. 60 Successful completion of the synthesis was enabled by development of three key transformations: the Ti(III)-mediated cyclization of 12, the unusual Shapiro-type fragmentation of 11 as part of an auxiliary ring strategy, and the previously undescribed Aucatalyzed spirocyclization of a β-keto(enol)lactone (7) . We anticipate that these extensions to the synthetic toolkit will find wider application in the preparation of complex structures and that ongoing investigations into the chemistry and biology of natural product frameworks exemplified by 1, and more particularly 18, will prove to be fruitful fields of research.…”