Total Syntheses of Picrotoxanes

When Porter and Coscia published their reviews (2, 3) no total synthesis of a picrotoxane had come forth. Even the partial syntheses were not well developed, as mubironine A (97), an oxidation product of dendrobine (82), was not known as natural product at that time. The same is true for nordendrobine, the demethylation product of dendrobine (82), now known as mubironine B (98). Partial syntheses in the 1970s were made to determine the structure or absolute configuration of new picrotoxanes and are described earlier in this chapter. 

When the first picrotoxane syntheses were published Corey s rules for S3mthesis planning and the Woodward-Hojfmann rules had just become common knowledge as well as the necessity to prepare physiologically active products in an enan-tiomerically pure form. 

Due to their more simple structures, the syntheses of the sesquiterpene alkaloids, the dendrobines, were mastered first. 

Eight years after the structure elucidation of dendrobine (82) was completed, two total syntheses of this highly crowded tetracyclic compound with its seven stereogenic centers were published. To date, seven total syntheses and five formal syntheses have been reported. Those synthesis efforts nicely reflect trends in total synthesis over the last decades, which shall be demonstrated by the stereoselective construction of the quaternary center, a formidable task even today. 

Heathcock used as concerted cycloaddition intramolecular photochemical (2 + 2) addition to create the quaternary center in his projected synthesis. A cationic rearrangement Wagner-Meerwein rearrangement) was intended as further key step but failed (162). 

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