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.