A Synthesis of Alsmaphorazine B Demonstrates the Chemical Feasibility of a New Biogenetic Hypothesis

An N-oxide fragmentation/hydroxylamine oxidation/intramolecular
1,3-dipolar cycloaddition cascade efficiently converted an oxidized
congener of akuammicine into the complex, hexacyclic architecture
of the alsmaphorazine alkaloids. This dramatic structural change shows
the chemical feasibility of our novel proposal for alsmaphorazine
biogenesis. Critical to these endeavors was a marked improvement in
our previously reported Zincke aldehyde cycloaddition approach to
indole alkaloids, which permitted the gram-scale synthesis of akuammicine.
The chemoselective oxidations of akuammicine leading up to the key
rearrangement also generated several biogenetically related alkaloids
of the alstolucine and alpneumine families.