Jian-Rong Wang

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

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 Moshers method. In addition, the structures of dyvariabilin H (10c) proposed by Sticher et al. and cneorin-NP(36) (11b) by Mondon et al. were corrected as 10 and 11, respectively. Toonapubesin G (7) showed promising inhibitory activity against CDC25B with an IC(50) value of 2.1 μM, while compound 8a showed significant cell protecting activity against H(2)O(2)-induced SH-SY5Y cell damage with 11.5% increase in cell viability.

Extending the record of bis-γ-pyrone polypropionates from marine pulmonate mollusks.

The isolation and structure elucidation of 10 unreported polypropionate metabolites (compounds 6-15), structurally related to either ilikonapyrone (1) or onchidione (3), from two onchidiid pulmonate mollusk species are discussed. Structure elucidation was achieved by NMR spectroscopy and chemical correlation with model compounds. Evaluation of in vitro growth-inhibitory properties in human cancer cells was also carried out on some of the isolated polypropionates including previously reported onchidione metabolites.

Structural diversity of terpenoids in the soft coral Sinularia flexibilis, evidenced by a collection from the South China Sea

Eight new terpenoids, including six α-methylene-δ-lactone-bearing cembranoids (1–6), a 15-membered macrocyclic diterpenoid (7), and a biscembranoid (8), were isolated from South China Sea soft coral Sinularia flexibilis, along with five known analogues (9–13). Their structures including relative stereochemistry were elucidated by detailed spectroscopic analyses, chemical reactions and by comparison with literature data. Further, the structures of 8 and 10 were unambiguously confirmed by X-ray diffraction analyses. Compound 7, named epoxyflexibilene, represents the second 15-membered macrocyclic diterpenoid being discovered from marine sources, whereas sinulaflexiolide L (8) is the third member of the extremely rare cembrane dimers connected through C–C single bond. The discovery of these new isolates showed the high chemical diversity and ecological complexity of the animal S. flexibilis collected in different locations. In a bioassay, compound 9 exhibited potent anti-tumor activity targeting the inositol-requiring 1/X-box-binding protein 1 (IRE1/XBP1) signaling pathway.

Structural and stereochemical studies of five new pregnane steroids from the stem bark of Toona ciliata var. pubescens.

Five new pregnane steroids, toonasterones A (1), B (2), (Z)-aglawone (3), (Z)-toonasterone C (4), and (E)-toonasterone C (5), were isolated from the stem bark of Toona ciliata var. pubescens. Their structures were elucidated by means of detailed spectroscopic (IR, MS, and 2D NMR) analysis, and the stereochemistry of 1 was secured by X-ray diffraction analysis. (Z)-aglawone (3) exhibited moderate inhibitory activity of protein tyrosine phosphatase 1B (PTP1B), a potential drug target for treatment of type-II diabetes and obesity, with an IC(50) value of 1.12 μg/mL.

Design, synthesis and biological evaluation of novel chiral oxazino-indoles as potential and selective neuroprotective agents against Aβ25-35-induced neuronal damage.

A series of chiral oxazino-indoles have been synthesized via a key intermolecular oxa-Pictet-Spengler reaction. These compounds exhibited significant and selective neuroprotective effects against Aβ25-35-induced neuronal damage. This is the first report of evaluating the influence of chiral diversity of oxazino-indoles on their neuroprotective activities, with the structure-activity relationship been analyzed. The highly active compounds 3f, 3g, 4g, 4h, and 6b all performed over 90% cell protection, providing a new direction for the development of neuroprotective agents against Alzheimers disease.

Clavuridins A and B, two new trinor-guaiane sesquiterpenes isolated from the Xisha soft coral Clavularia viridis

In the present study, two new trinor-guaiane sesquiterpenes, named clavuridins B (1), and A (2), along with three known sesquiterpenes (3-5), were isolated from the Xisha soft coral Clavularia viridis. Their structures and absolute configurations were determined on the basis of spectroscopic analysis, X-ray diffraction analysis with Cu Kα radiation and by comparison with related model compounds. Compounds 1 and 3-5 were evaluated for their cytotoxic activity.