The first total synthesis of daphgraciline
has been achieved,
which
also represents the first example of the synthesis of Daphniphyllum yuzurine-type alkaloids (∼50
members). The unique bridged azabicyclo[4.3.1] ring system in the
yuzurine-type subfamily was efficiently and diastereoselectively assembled
via a mild type II [5+2] cycloaddition for the first time. The compact
tetracyclic [6–7–5–5] skeleton was installed
efficiently via an intramolecular Diels–Alder reaction, followed
by a benzilic acid-type rearrangement. The synthetically challenging
spiro tetrahydropyran moiety in the final product was installed diastereoselectively
via a TiIII-mediated reductive epoxide coupling reaction.
Potential access to enantioenriched daphgraciline is presented.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.