Terpenoids-XCI: transformation products of costunolide. Stereochemistry of (-) santonin and solid dihydrocostunolide at C11

Abstract

Solid dihydrocostunolide (VI), on metal-amine reduction furnishes an acid, C₁₅H₂₄O₂ (VII; R = H), the constitution of which has been decided from spectral evidence and confirmed by conversion into the known primary alcohol (V) and the hydrocarbon (IV). Conclusive evidence in support of VII (R = H), and the stereochemistry at C₄ have been obtained from the ozonolysis of VII (R = CH₃) which gives as one of the products, S-(+)-α-methylglutaric acid dimethyl ester (VIIIa), a compound of known absolute configuration. The other product of ozonolysis, (-)-2-methyl-3 (3'-oxo)-butylsuccinic acid dimethyl ester (VIIIb), is converted into (-)-2S-methyl-3S-butylsuccinic acid dimethyl ester (XV), via desulphurization of its thioketal, which proves the α-orientation of the CH₃ group at C₁₁ in both (-)-santonin (X) and dihydrocostunolide (VI). This for the first time provides a chemical proof obtained under mild experimental conditions for the stereochemistry at the centre C₁₁. Acid catalysed cyclization of VII (R = H), furnishes a bicyclic acid, C₁₅H₂₄O₂ (XVII; R = H), and santanolide 'c' (IX); the formation of the latter confirms the assignment of stereochemistry at C₄. α-Cyclodihydrocostunolide (XXVIII), obtainable from both VI and I, has been converted into (+)-isojunenol (XXVII) and dihydro (+)-junenol (XXXIII).