Immunosuppressive Nor-isopimarane Diterpenes from Cultures of the Fungicolous Fungus Xylaria longipes HFG1018

Eighteen new nor-isopimarane diterpenes, xylarinorditerpenes A–R (1–18), along with two previously reported compounds, 14α,16-epoxy-18-norisopimar-7-en-4α-ol (19) and the labdane-type diterpene agatadiol (20), were isolated from cultures of the fungicolous fungus Xylaria longipes HFG1018 isolated from the wood-rotting basidiomycete Fomitopsis betulinus. The structure elucidation and relative configuration assignments of 1–18 were accomplished by interpretation of spectroscopic data and through computational methods. The absolute configurations of 1, 4, and 16 were determined by single-crystal X-ray diffraction. Compounds 1–16 possess an 18- or 19-nor-isopimarane skeleton, and compounds 17 and 18 possess an 18,19-dinor-isopimarane skeleton. Compounds 2–5, 9, 14, 19, and 20 showed immunosuppressive activity but were devoid of cytotoxicity against the cell proliferation by concanavalin A-induced T lymphocytes and lipopolysaccharide-induced B lymphocytes, with IC50 values varying from 1.0 to 27.2 μM and from 16.1 to 51.8 μM, respectively.