Total Synthesis of Gelsemoxonine through a Spirocyclopropane Isoxazolidine Ring Contraction

Plants of the species Gelsemium have
found application in traditional Asian medicine for over a thousand
years. Gelsemoxonine represents a novel constituent of this plant
incorporating a highly functionalized azetidine at its core. We herein
report a full account of our studies directed toward the total synthesis
of gelsemoxonine that relies on a conceptually new approach for the
construction of the central azacyclobutane. A spirocyclopropane isoxazolidine
ring contraction was employed to access a key β-lactam intermediate,
which could be further elaborated to the azetidine of the natural
product. In the course of our studies, we have gained detailed insight
into this intriguing transformation. Furthermore, we report on previously
unnoticed oligomerization chemistry of gelsemoxonine. We also document
an enantioselective synthesis of a key precursor en route to gelsemoxonine.