Total synthesis of Podophyllum lignans - An exploratory study

Approaches to podophyllotoxin 1c involving electrophilic ring closure as the crucial step have until now failed to produce the tetralin framework with the correct relative configuration. Stereochemical considerations allowed us to propose 18b as a precursor, in which the cis-substituted dioxane ring could be an essential stereocontrolling element. 18b was obtained with low selectivity via aldol condensation of 16. The crucial ring closure failed because of the high reactivity under Lewis acid conditions of the oxygen at C-4, when incorporated in a 2-phenyl-1, 3-dioxane.Approaches to podophyllotoxin 1c involving electrophilic ring closure as the crucial step have until now failed to produce the tetralin framework with the correct relative configuration. Stereochemical considerations allowed us to propose 18b as a precursor, in which the cis-substituted dioxane ring could be an essential stereocontrolling element. 18b was obtained with low selectivity via aldol condensation of 16. The crucial ring closure failed because of the high reactivity under Lewis acid conditions of the oxygen at C-4, when incorporated in a 2-phenyl-1, 3-dioxane.