Four Novel Quassinoid Skeletons from Brucea mollis via Guided Separation and Biomimetic Synthesis.

Seven undescribed quassinoids (1-7) and one known quassinoid (8) were obtained from Brucea mollis by molecular networking integrated with DeepSAT and SIRIUS. Compound 1 is the first alkaloid-quassinoid adduct featuring a novel 6/5/5/6/6/6-fused hexacyclic skeleton. Compounds 2 and 3 are unprecedented skeleton C19 quassinoids. Biosynthetic pathways were proposed, which guided the successful biomimetic synthesis of compound 1, affording an optimized yield of 23.2%. Byproduct 1a with a rare 5/6/5/6/6/6 core was also formed.