Nature knows best: an amazing reaction cascade is uncovered by design and discovery.
The Daphniphyllum alkaloids are a group of highly complex polycyclic alkaloids. Examination of the structures if several members of this family of natural products led to a hypothesis about their mode of biosynthesis (depicted in Scheme I). Based on this hypothetical biosynthetic pathway, a laboratory synthesis was designed that incorporated as a key transformation the novel one-pot transformation of dialdehyde 24 to pentacyclic unsaturated amine 25. This process turned out to be an exceptionally efficient way to construct the pentacyclic nucleus of the Daphniphyllum alkaloids. However, a purely fortuitous discovery, resulting from accidental use of methylamine rather than ammonia, led to a great improvement in the synthesis and suggests an even more attractive possible biosynthesis.
Heathcock
C H
CH
Department of Chemistry, University of California, Berkeley 94720, USA. chh@alkaloid.cchem.berkeley.edu
D000470:Alkaloids / Q000096:biosynthesis* / Q000737:chemistry; D010944:Plants / Q000737:chemistry / Q000378:metabolism*
D000470:Alkaloids