Synthesis of Demissidine Analogues from Tigogenin via Imine Intermediates

A five-step transformation of a spiroketal side chain of tigogenin into an indolizidine system present in solanidane alkaloids such as demissidine and solanidine was elaborated. The key intermediate in the synthesis was spiroimine 3 readily obtained from tigogenin by its RuO4 oxidation to 5,6-dihydrokryptogenin followed by amination with aluminum amide generated in situ from DIBAlH and ammonium chloride. The mild reduction of spiroimine to a 26-hydroxy-dihydropyrrole derivative and subsequent mesylation resulted in the formation of 25-epidemissidinium salt or 23-sulfone depending on reaction conditions.

Automated summary

The study elaborated a five-step transformation of a spiroketal side chain of tigogenin into an indolizidine system present in solanidane alkaloids. The key intermediate in the synthesis, spiroimine 3, was readily obtained from tigogenin by oxidation and amination. Subsequent mild reduction and mesylation resulted in the formation of different products depending on reaction conditions.