Isolation and Characterization of Antifungal Metabolites from the Melia azedarach-Associated Fungus Diaporthe eucalyptorum.

Two biosynthetically related new metabolites, eucalyptin A (1) and eucalyptin B (2), along with six known compounds (3-8), eugenitol (3), cytosporone C (4), 4-hydroxyphenethyl alcohol (5), 1-(4-hydroxyphenyl)ethane-1,2-diol (6), N-(2-hydroxy-2-phenylethyl)acetamide (7) and phomopene (8), were isolated from the solid rice cultures of the endophytic fungus Diaporthe eucalyptorum KY-9, associated with Melia azedarach. In addition, two further new derivatives (2a, 2b) were prepared from 2. Their structures were elucidated by exhaustive analysis of NMR and ESIMS data, and chemical transformations. Compound (1) was identified as a rare polyketide fatty acid, (8E)-3,5,11-trihydroxy-2,10,12-trimethyltetradecenoic acid, and 2 is the first cyclic depsipeptide containing the same fatty acid residue as 1. The compound 2 are a member of the cyclic depsipeptides family and are based on a tripeptide chain composed by Gly-Gly-Thr. Its N-terminal end is N-acylated by an 11-hydroxy fatty acid with branch alkyl chain of 14:1. The 11-hydroxyl group closes a 22-membered lactone ring with the carboxylic group of the C-terminal amino acid. The isolated compounds were tested for their inhibitory activity against the four plant pathogenic fungi Alternaria solani, Botrytis cinerea, Fusarium solani, and Gibberella saubinettii. Compounds 1, 4, 6, and 7 exhibited antifungal activities against the pathogens, Alternaria solani with minimal inhibitory concentration (MIC) values from 6.25 to 50 μM. Thus, strain KY-9 represents an untapped source for the development of biological control agents to prevent the infection of pathogenic fungus A. solani.