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.