(−)- And (+)-securidanes A and B, natural triarylmethane enantiomers: Structure and bioinspired total synthesis

Abstract

Two pairs of enantiomers, (−) and (+)-securidanes A (1 and 2) and B (3 and 4) featuring unprecedented triarylmethane (TAM) skeletons, were isolated from Securidaca inappendiculata. Their structures were established by spectroscopic data, X-ray crystallography, and CD analysis. A plausible biosynthetic pathway for 1−4 based on the co-isolated precursors was proposed. Bioinspired total synthesis of 1−4 was completed in high yield, which in turn corroborated the biosynthetic hypothesis. Compounds 1−4 showed good inhibition against protein tyrosine phosphatase 1B (PTP1B). The molecular docking demonstrated that the strongest inhibitor 3 (IC50 = 7.52 μM) reaches deeper into the binding pocket and has an additional H-bond.