Total synthesis of (±)-specionin

Abstract

(±)-Specionin has been synthesized in a short, efficient sequence of reactions from (±)-exo, exo-6,7-bis(benzyloxy)-exo-4-(hydroxymethyl)-cis-bicyclo[3.3.0]oct-2-ene 5. The key feature of the synthesis is a ‘one-pot’ hydrogenolysis–cyclopentanediol cleavage–bis-acetal cyclisation on intermediate 21a, to provide specionin acetate stereoselectively. The 1β-H, 3α-H stereochemical arrangement of specionin is shown to be thermodynamically preferred and, with the functionality of the left-hand ring complete, the stereochemistry of the ethyl acetals is controlled by equilibration. A diastereoisomer of specionin acetate, 26a, has also been prepared from (±)-exo, exo-6,7-bis(benzyloxy)-endo-2-(hydroxymethyl)-cis-bicyclo[3.3.0]oct-2-ene 6a, by an analogous series of reactions.