Isolation and structure elucidation of the new fungal metabolite (-)-xylariamide A

Chemical investigations of the terrestrial microfungus Xylaria sp. have afforded the new natural product (-)-xylariamide A (1). The gross structure of 1 was determined by interpretation of 1D and 2D NMR, UV, IR, and MS data. Confirmation of the structure and the absolute stereochemistry of 1 were determined by the total synthesis of (+)-xylariamide A (2). Synthetic 2 was produced by N,O-bis(trimethylsilyl)acetamide-induced coupling of 3-chloro-L-tyrosine (3) with (E)-but-2-enedioic acid 2,5-dioxo-pyrrolidin-1-yl ester methyl ester (4). Optical rotation comparison of 1 with 2 indicated that the natural product (1) contained 3-chloro-D-tyrosine. Both enantiomers of xylariamide A were tested in a brine shrimp lethality assay, and only the natural product (1) showed toxicity.