Protolimonoids and norlimonoids from the stem bark of Toona ciliata var. pubescens

Abstract

Six new tirucallane protolimonoids, toonapubesins A–F (1–6), one new rearranged tirucallane protolimonoid, toonapubesin G (7), and two new 21,22,23-trinorapotirucallane limonoids, toonapubesic acids A (8) and B (9), possessing an unprecedented carbon skeleton, along with five known tirucallane protolimonoids (10–14) and one known apotirucallane limonoid (15), were isolated from the stem bark of Toona ciliata var. pubescens. Their structures and relative configurations were determined by detailed spectroscopic analysis and by chemical methods. The proposed structures of 8 and 11 were confirmed by X-ray diffraction analysis of their respective derivatives (8a and 11a). The absolute configuration of 8 was determined by a novel solid-state TDDFT ECD approach on its derivative 8a while the absolute configuration of 10 was determined by the modified Mosher's method. In addition, the structures of dyvariabilin H (10c) proposed by Sticher et al. and cneorin-NP₃₆ (11b) by Mondon et al. were corrected as 10 and 11, respectively. Toonapubesin G (7) showed promising inhibitory activity against CDC25B with an IC₅₀ value of 2.1 μM, while compound 8a showed significant cell protecting activity against H₂O₂-induced SH-SY5Y cell damage with 11.5% increase in cell viability.