Decalactone Derivatives from Corynespora cassiicola, an Endophytic Fungus of the Mangrove Plant Laguncularia racemosa

• Published in: European journal of organic chemistry Vol. 2012; no. 18; pp. 3476 - 3484
• Main Authors: Ebrahim, Weaam, Aly, Amal H., Mándi, Attila, Totzke, Frank, Kubbutat, Michael H. G., Wray, Victor, Lin, Wen-Han, Dai, Haofu, Proksch, Peter, Kurtán, Tibor, Debbab, Abdessamad
• Format: Journal Article
• Language: English
• Published: Weinheim WILEY-VCH Verlag 01.06.2012; WILEY‐VCH Verlag; Wiley; Wiley-VCH
• Subjects: Biological and medical sciences; Chemistry; Chemistry, Organic; Conformation analysis; Drug discovery; Exact sciences and technology; Fungi; General pharmacology; Heterocyclic compounds; Heterocyclic compounds with o, s, se, te hetero atom and condensed derivatives; Lactones; Medical sciences; Medicinal chemistry; Natural products; Organic chemistry; Pharmacognosy. Homeopathy. Health food; Pharmacology. Drug treatments; Physical Sciences; Preparations and properties; Science & Technology; Structure elucidation; Asia; China; Conformation analysis; CURVULARIN; HEPTAKETIDES; Medicinal chemistry; TOLERANCE; SALT-STRESS; CYTOTOXIC METABOLITES; BIOACTIVE METABOLITES; Lactones; Fungi; Natural products; POLYKETIDES; Drug discovery; INHIBITORS; Structure elucidation; DEHYDROCURVULARIN; CONSTITUENTS; High resolution; Molecular structure; Metabolite; Non-specific serine/threonine protein kinase; Conformational analysis; NMR spectrometry; Oxygen heterocycle; Medicinal plant; Folk medicine; Mangrove; Dicotyledones; Angiospermae; Fungi Imperfecti; Human; Drug; Enzyme; Pharmacognosy; Transferases; Theoretical study; Lactone; Plant leaf; Natural compound; Acetic acid ethyl ester; Corynespora cassiicola; Combretaceae; Kinase; Absolute configuration; Plant origin; Optical activity; Density functional method; Endophyte; Isolation; Spermatophyta; Mass spectrometry; Structural analysis; Conformation
• ISSN: 1434-193X; 1099-0690
• DOI: 10.1002/ejoc.201200245

Chemical investigation of the ethyl acetate extract of Corynespora cassiicola, isolated from leaf tissues of the Chinese mangrove medicinal plant Laguncularia racemosa, yielded four new secondary metabolites, including three decalactones, xestodecalactones D–F (1–3) as well as corynesidone C (4), in addition to four known compounds. The structures of the new compounds were determined on the basis of one‐ and two‐dimensional NMR spectroscopy as well as by high‐resolution mass spectrometry. Absolute configurations of the optically active compounds 1–3 were determined by TDDFT ECD calculations of their solution conformers, proving that they belong to the (11S) series of xestodecalactones, opposite to the (11R) configuration of the known xestodecalactones A–C. All compounds were tested against a panel of human protein kinases. Among the isolated compounds, two inhibited several kinases such as IGF1‐R and VEGF‐R2 with IC50 values mostly in the low micromolar range. Three new xestodecalactones D–F (1–3) and a new corynesidone C were isolated from Corynespora cassiicola. The structures were determined by 1D and 2D NMR spectroscopy as well as by high‐resolution mass spectrometry. The absolute configurations of 1–3 were determined by TDDFT ECD calculations. All compounds were tested against a panel of human protein kinases.