Conversion of Gibberellic Acid into the B-Ring seco-Kaurenoid, Longirabdolactone

Abstract

The base-catalyzed rearrangement of an α-hydroxy aldehyde derived from the gibberellin GA₁₅ results in ring-expansion of the five-membered B-ring of the gibberellin molecule and transformation into an ent-kaurene derivative. Further manipulation affords 19,7-acetals and access to the highly functionalized B-ring seco-kaurenoid bioactive secondary metabolites that have been isolated from the genus Rabdosia. The methodology is illustrated by the synthesis of longirabdolactone from gibberellic acid. Unanticipated and unobserved epimerization at C5 led initially to the 5-epimer of the synthetic target by a series of ketol rearrangements, but the isomerization could be avoided through the use of milder reaction conditions.