Graphislactone A

The extracts derived from cultures of 1626 endophytic strains harbored in Trachelospermum jasminoides were assayed for more potent antioxidant and/or free radical-scavenging agents. The free radical-scavenging assessment was carried out using l,l-diphenyl-2-picrylhydrazyl (DPPH) and hydroxyl radical assays, and the antioxidant actions on linoleic acid and human low-density lipoprotein (LDL) models. After extensive spectroscopic analyses, graphislactone A was characterized as the most bioactive secondary metabolite of endophytic Cephalosporium sp. IFB-E001 with its free radical-scavenging (in a dose-dependent manner) and antioxidant activities ascertained in vitro to be stronger than those of butylated hydroxytoluene (BHT) and ascorbic acid, the two positive references coassayed in the study. From the demonstrated efficacy of graphislactone A in preventing and protecting against oxidative injury, it can be predicted that this metabolite could be a potential agent in the management of oxidative damage-initiated diseases.

Seven compounds belonging to different structural skeletons were isolated from Microsphaeropsis olivacea grown in liquid and solid media. The enalin derivative 7-hydroxy-2,4-dimethyl-3(2H)-benzofuranone is reported for the first time, while additional spectroscopic information is provided for the acetates of botrallin and ulocladol. The activity of the isolated compounds was assessed towards the enzyme acetylcholinesterase (AChE) and their cytotoxicity against human lung fibroblasts. Graphislactone A and botrallin presented a moderate activity towards AChE, with IC50 of 8.1 and 6.1 microg/ml (27 and 19 microM, respectively). Under the same experimental conditions, the IC50 of the standard inhibitor galanthamine was 3 microg/ml. The cytotoxicity of both compounds was > 1000 and 330 microM, respectively. None of the compounds was promising as antibacterial or antifungic against phytopathogenic fungi and bacteria. Botrallin and graphislactone A were detected in the liquid potato-dextrose and yeast extract/malt extract/dextrose as well as on a solid substrate (rice). Butyrolactone I was obtained from the fungus growing on solid medium.

A palladium-mediated intramolecular aryl-aryl coupling reaction was applied to the total synthesis of the bioactive natural products, graphislactone G (1), and palmariols A (2) and B (3), which possess an unusual chloro-subsutituent on the 6H-dibenzo[b,d]pyran-6-one skeleton. Based on the transition state model of the coupling reaction, the mechanistic aspect for the regioselectivity of the aryl-aryl coupling reaction is also discussed.