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

Abstract

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 IC 50 values varying from 1.0 to 27.2 μM and from 16.1 to 51.8 μM, respectively.

Recent progress in biodiversity research on the Xylariales and their secondary metabolism

“…Moreover, several nor-isopimarene terpenoids named xylarinoditerpenes A-R [37] and two isopimarenes designated xylarilongipins A (17) and B [38] were recently reported. These terpenoids were isolated from a fungicolous strain of X. longipes, growing on fruiting bodies of the basidiomycete Fomitopsis betulina.…”

Immunosuppressive Isopimarane Diterpenes From Cultures of the Endophytic Fungus Ilyonectria robusta

“…Interestingly, these diterpenes are generally obtained from plants and fungi, which showed diverse bioactivity ( Reveglia et al, 2018 ). Until now, isopimarane diterpenes with immunosuppressive activity were first reported in 2020 ( Chen et al, 2020 ). This research provides several isopimarane scaffolds with potential immunosuppressive activity and enriched structure diversity.…”

“…Diterpenoids derived from C20 precursor ( E , E , E )-geranylgeranyl diphosphate with more than 12,000 described compounds ( Quin et al, 2014 ; Zi et al, 2014 ). Some isopimarane diterpenes with immunosuppressive activity have been reported ( Chen et al, 2020 ).…”

Meroterpenoids with Potent Immunosuppressive Activity from Fungus Bipolaris zeicola

“…[ 1 ] Since cyclosporine A was demonstrated to be effective for preventing the organ‐graft rejection in 1978, many representative natural immunosuppressive drugs, e.g ., tacrolimus, mycophenolic acid, and rapamycin, have been developed from microbial natural products. [ 2‐3 ] However, these widely used immunosuppressive drugs showed undesirable side effects, such as liver toxicity and renal injury, [ 4 ] giving rise to urgent need for alternatives with high efficacy and low toxicity.…”