Structural Elucidation and Total Synthesis of Trichodermotin A, A Natural α‐Glucosidase Inhibitor from Trichoderma asperellum

Comprehensive Summary A pair of alkaloid enantiomers possessing a novel 1‐oxaspiro[4.4]non‐3‐ene‐2,7‐dione skeleton, trichodermotin A (1), was obtained from the fungus Trichoderma asperellum . Spectroscopic data, X‐ray diffraction, and ECD calculations were used to establish its structure and absolute configuration. (−)‐1 showed significant α ‐glucosidase inhibitory activity (IC 50 = 10.1 μmol/L vs. 60.1 μmol/L of positive control). A plausible biosynthetic pathway originating from L ‐ β ‐phenylalanine was proposed, and a facile total synthesis was further accomplished. The key reaction of our synthetic strategy was a domino aza‐Michael/lactonization in one pot, leading to the pivotal 4‐amino‐oxaspiro[4.4]octane scaffold.