Paranolin: A New Xanthene‐Based Metabolite from Paraphaeosphaeria nolinae.

Abstract

A new xanthene-based, polycyclic metabolite, paranolin (= (2R,3aS,12aR)-3,3a-dihydro-3a-hydroxy-8-(hydroxymethyl)-2-(1-hydroxy-1-methylethyl)-9-methoxy-10-methylfuro[3,2-d]xanthen-6(2H)-one; 1) was isolated from a culture of Paraphaeosphaeria nolinae (IFB-E011), an endophytic fungus residing in the normal stem of the artemisinin-producing plant Artemisia annua (Asteraceae). The structure of 1 was elucidated by extensive spectroscopic analyses. Although not substantially active against the human colon (SW1116) and human cervical carcinoma (Hela) cell lines, this metabolite seems to be the first example of a xanthene-derived secondary metabolite. Its possible biosynthetic origin (Scheme) and its significance as a phyllogenetic marker are discussed in brief.

Antimicrobial dihydrobenzofurans and xanthenes from a foliar endophyte of Pinus strobus

“…To our knowledge, paranolin, isolated from Paraphaeosphaeria nolinae (IFB-E011) (Pleosporales), an endophyte of wormwood (Artemisia annua; Ge et al, 2006) is the only previous report of a fungal derived xanthene natural product. Various xanthenes exhibit anticancer (Chatterjee et al, 1996), antivenom (Selvanayagam et al, 1996), cytotoxic (Huang et al, 2010) and antifungal (Krasnoff et al, 1999) activity.…”

Chemical and Functional Diversity of Natural Products from Plant Associated Endophytic Fungi

“…An endophytic fungal strain from Torreya mairei was identified as Aspergillus clavatonanicus by analysis of its morphological characteristics and the sequences of the internal transcribed spacers (ITS) of rDNA. When grown in surface culture, the fungus produced clavatol 46 57Nigrosporalactone (58) plant pathogens, Aspergillus niger, Botrytis cinerea, Fusarium avenaceum, F. moniliforme, Helminthosporium maydis, Penicillium islandicum, and Ophiostoma minus, using the dose-dependent paper-disk diffusion method, and all five compounds showed weak antifungal activities. Compound 52 was the most potent, with MIC values in the range 31.25-500 μg mL -1 .…”

“…Microcarpalide (23), a novel microfilamentdisrupting agent with weak cytotoxicity to mammalian cells, was characterized from an unidentified fungus in Ficus microcarpa L[57]. A new xanthene based metabolite, paranolin (24) was characterized from an endophytic strain of Paraphaeosphaeria nolinae IFB-E011 from Artemisia annua, (Asteraceae)[58].Recently, a novel compound from a Phomopsis sp. endophytic on Adenocarpus foliolosus was isolated and identified as phomosine G (25)[59].…”

NF-κB inhibitors, unique γ-pyranol-γ-lactams with sulfide and sulfoxide moieties from Hawaiian plant Lycopodiella cernua derived fungus Paraphaeosphaeria neglecta FT462

“…Paraphaeosphaeria species produce different types of secondary metabolites, including macrolides 28 , 29 , xanthenes 30 , isocoumarins 31 , hexaketide 32 , polyketides 33 , 34 , and phaeosphaerides 2 and paraphaeosphaerides 1 , 2 , 8 , 35 . Paraphaeosphaeride A 2 is the first sulfur-containing molecule (a sulfide) isolated from Paraphaeosphaeria species.…”