A Concise, Enantiospecific Total Synthesis of Chilocorine C Fueled by a Reductive Cyclization/Mannich Reaction Cascade

Among defensive alkaloids isolated
from ladybugs, the heterodimeric
member chilocorine C possesses an alluring monomeric unit that combines
quinolizidine and indolizidine substructures. Indeed, the overall
stereochemical disposition of its ring fusions is distinct from those
of related natural products. Herein we show that a carefully orchestrated
sequence with several chemoselective transformations, including a
designed cascade that accomplishes nine distinct chemical reactions
in one-pot, can smoothly forge that domain and ultimately enable a
15-step, 11-pot enantiospecific synthesis of the natural product.
Mechanistic studies, density functional theory calculations, and the
delineation of several other unsuccessful approaches highlight its
unique elements.