On the biometric transformation of aporphine alkaloids to taspinoids

Taspine, an optically inactive tertiary base, is the principal alkaloid in the latex of the South American jungle trees, genus Croton (Euphorbiacea), most commonly C. lechleri. This latex is widely used throughout South America as a folk medicine for wound treatment and is known as "Sangre de Grado" or dragons blood because of its red color. Taspine is considered a rare alkaloid, having been found in only one other plant species, Leontice ewersmanni, lion's tail (Berberidacea), and no structurally related alkaloids have been isolated as natural products. Thus synthesis is the only entry to this class of compounds, the taspinoids.; A potentially general route for transforming aporphine alkaloids into taspinoids has been developed. This conversion employed an elimination-oxidation sequence patterned on the presumed biogenetic relationship between these alkaloid types. Aporphines with varying ring-substitutions were used as starting materials: magnoflorine/isocoryidine, boldine, and apomorphine/apocodeine. Initial attempts to effect elimination starting with quaternary aporphinoids was found to be a synthetically inefficient method for obtaining the desired phenathrene alkaloids. In contrast, treatment of tertiary aporphines with acetic anhydride led to formation of phenanthrenes in excellent yield in all cases attempted. Subsequent ozonolysis (and reduction of the ozonide mixture) then furnished, in quantitative yield, the corresponding 2,2{dollar}spprime{dollar}-biaryidialdehydes. This simple two-step procedure was used to convert isocorydine, boldine, apomorphine and apocodeine into seco-derivatives having the biphenylethyl amine carbon-nitrogen skeleton characteristic of taspinoids. Oxidation of these biaryldialdehydes required rigorous conditions, aqueous alkaline potassium permanganate with a phase transfer agent proved most effective furnishing good yields of 2,2{dollar}spprime{dollar}-biaryldicarboxylic acids. Finally, amide hydrolysis and subsequent reductive methylation gave amino dicarboxylic acids, analogues of taspinic acid.