Aglatestine A, a Rearranged Limonoid with a 3/6/6 Tricarbocyclic Framework from the Fruits of Aglaia edulis

Abstract

Aglatestine A (1), an unprecedented 3/6/6 tricarbocyclic limonoid framework along with four biogenic A/D-seco limonoid analogues with rare β-substituents at C-6 (2-5), was discovered from the fruits of Aglaia edulis. The structures of 1-5 along with their absolute configurations were clarified using methods of HRMS(ESI), NMR, electronic circular dichroism, X-ray diffraction crystallography, and quantum chemical calculations. The plausible biogenetic speculation suggested that an electrophilic cyclization between C-1 carbocation from acetolysis and electron-rich C-5 from enolization of C═O of 2 may play a key role. The biological evaluation showed that 5 exhibited anti-inflammatory activity indicated by inhibiting NO release in LPS-activated RAW 264.7 macrophages (IC50: 35.72 ± 1.96 μM).