Enantiospecific formal total synthesis of homogynolide-A

Abstract

Formal total synthesis of both enantiomers of homogynolide-A, a sesquiterpene containing an α-spiro-β-methylene-γ-butyrolactone moiety fused to a bicyclo[4.3.0]nonane framework, is described. Thus, (R)-carvone was converted into both enantiomers of 3-methylcarvone 14. A reductive allylation, Wacker oxidation and intramolecular aldol condensation sequence transformed 3-methylcarvone into the hydrindanone 18. Regiospecific reduction of the enone followed by a three step degradation of the isopropenyl group converted the hydrindanone 18 into the dione 21, which on regioselective ketalisation furnished the key intermediate ketoketal 13. Methoxymethylene Wittig reaction followed by bromoacetalisation reaction transformed the ketoketal 13 into the bromoacetal 23. The 5-exo-dig radical cyclisation of the bromoacetal 23 followed by the hydrolysis and oxidation of the resultant spiroacetal 24 furnished a 1:4 mixture of the Greene's precursor ketospirolactone 12 and its spiroepimer 26.

Carvone as a Versatile Chiral Building Block for Total Syntheses of Heterocyclic Sesquiterpenoids

“…Stereoselective reduction of the ketone 18 followed by esterification with a mixed anhydride of tigilic acid and 2,4,6-trichlorobenzoic acid 19 afforded (+)-homogynolide A (20). Srikrishna and Reddy took an alternative radical approach for introduction of the -methylene-spirolactone moiety in the synthesis of an antipode of Greene's intermediate 18 (Scheme 3) [11]. 1,3-Dipolar cycloaddition of S-(+)-carvone (1) with diazomethane and subsequent thermolysis of the resulting Syntheses of heterocyclic sesquiterpenoids starting from carvone Natural Product Communications Vol.…”