Stereospecific Synthesis of 9α-(Acetoxymethyl)-8α,8'-epoxy-3α,4,4-trimethyl-trans-decalin-1α-ol Acetate, a Model for the Investigation of Structure-Activity Relationships of the Insect Antifeedant Neoclerodanes

Article abstract of DOI:10.1021/jo00330a013

The stereospecific synthesis of 9α-(acetoxymethyl)-8α,8'-epoxy-3α,4,4-trimethyl-trans-decalin-1α-ol acetate (3) is described.This compound represents the decalin portion of the insect antifeedant diterpenes with the neoclerodane skeleton such as clerodin (1) and ajugarin I (2) and can therefore serve as a model compound for the investigation of structure-activity relationships.Octalone 8 is a key intermediate in the synthesis of 3.Reductive alkylation of 8 gives the trans-decalone 9 which is transformed into the α,β-unsaturated ketone 10.An equatorial methyl at C-3 and carbonyl group at C-1 are introduced by means of an alkylative carbonyl transposition followed by catalytic hydrogenation.Reduction of this carbonyl group followed by acetylation affords 14.Cleavage of the cyclic ether then gives 16, which in turn can be dehydrohalogenated to 17.Epoxidation of 17 gives the isomeric epoxides 3 and 19.Stereospecific epoxidation of 17 to 3 can be acomplished via diol 20.