Chemoinformatic Exploration of “Bioinspired Metabolomes” Illuminates Diacetyl Assembly Pathways Toward Nesteretal A‑Like Cage Molecules

An
appealing and challenging cage structure along with an unusual
biosynthetic pathway prompted us to explore an expeditious bioinspired
one-pot total synthesis of nesteretal A. An unconventional strategy
was chosen, and a cascade reaction starting from diacetyl was studied.
Under organocatalytic conditions mimicking an aldolase, nesteretal
A and a related cage analogue were anticipated by in silico metabolization, detected, targeted, and characterized.