ChemInform Abstract: Biologically Active Metabolites from Fungi. Part 5. Palmarumycins C1‐ C16 from Coniothyrium sp.: Isolation, Structure Elucidation, and Biological Activity.

Abstract

Twelve new spiro acetal metabolites, the palmarumycins C1-Cs, (1-8), CI1 (ll), C12 (12), C15 (15), c 1 6 (16), and three known representatives (10, 13, 14) of this new class of antibiotics were isolated from Coniothyrium sp. The compounds show antibacterial, antifungal and herbicidal activity at concentrations of 10-6-10-4 mom. The structures of palmarumycin C 2 (2), palmarumycin C3 (3), and palmarumycin C5 (5)were confirmed by X-ray structure analysis.In the preceding paper we described four new metabolites from Coniothyrium palmarum named palmarumycins CP,-CP,['l. In this paper the fermentation products of a different, unidentified Coniothyrium species (internal strain number 812) from soil from a forest on West Borneo are investigated. In contrast to strain 2014 ['] that only produces active metabolites when grown on semisolid agar, strain 812 produces a large variety of secondary metabolites in submerged fermentation culture. After 14-22 days at 25"C, the culture extract shows good activity against bacteria, fungi, and also garden cress seedlings (see ref.I21). The biodiagrams show strong inhibition against the test fungus Cladosporium cucumerinum in the regions of medium and high polarity, but only low activity in the less polar area. The compounds were located on TLC by UV light (254 nm) and by slow decomposition upon exposure to air resulting in dark brown spots. Altogether 50 1 of culture broth (extracts of the mycelium show no biological activity) were extracted exhaustively with ethyl acetate to afford 33.4 g of crude extract. The crude extract was suspended in methanol and filtered to afford a solid residue (2.0 g) that was analyzed separately (see Experimental).The culture extract was subjected to extensive column chromatography on silica gel with different eluants (see Experimental). Eleven pure compounds and three mixtures could thus be isolated from the extract. As in the preceding paper ['], the compounds were named palmarumycins C (C=Coniothyrium) because of their similar chemical structure to the palmarumycins CP and were further specified as C1 to c 1 6 with increasing TLC polarity. Structure ElucidationThe compound second in polarity [palmarumycin C2 (2);see Table 1 for Rf values, yields, and melting points (dec.) of all palmarumycins C] isolated in pure form from the filtrate crystallized in long pale yellow needles with m.p. 228°C(dec.) and [a]g = -341. A positive reaction with 2,4-dinitrophenylhydrazine and bromocresol green indicated a carbonyl and an acidic group. The presence of these functional groups was confirmed by bands at 1651 cm-' for a conjugated carbonyl group and at 3432 cm-' for hydroxy groups.The 'H-and 13C-NMR spectra again show the typical pattern and spin systems for palmarumycins CP1 and CP2[ll, notably for the unchanged 1,8-dihydroxynaphthalene fragment and the acetal carbon atom at 6 = 96.0. The major differences occur in the area at C-2 and C-3; the NMR signals are typical of neither the aliphatic (CP,) nor the olefinic (CP,) environment. The chemical shifts in the 'H...

Enhancement of diepoxin ζ production with in situ resin adsorption in mycelial liquid culture of the endophytic fungus Berkleasmium sp. Dzf12 from Dioscorea zingiberensis

“…1), a spirobisnaphthalene with various bioactivities, was first isolated from the endophytic fungus LL-07F725 associated with a tree growing in Panama by Schlingmann et al in 1993, and later from other fungal species such as Nattrassia mangiferae (Chu et al 1994), Coniothyrium sp. (Krohn et al 1994), Cladosporium sp. (Petersen et al 1994) and endophytic fungus Berkleasmium sp.…”

Spirobisnaphthalenes effectively inhibit carbonic anhydrase

“…Spirobisnaphthalenes derivatives (1)(2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16) were all determined to inhibit hCA I, with K i values ranging of 1.60-460.42 mM for spirobisnaphthalenes derivatives. Spirobisnaphthalenes derivatives (1)(2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16) were all found to inhibit hCA II, with K i values ranging of 0.39-419.42 mM for spirobisnaphthalenes derivatives.…”

“…The spirobisnaphthalenes exhibit a wide range of biological effects such as antifungal and antibacterial [1][2][3][4] , antimitotic 5 , antileishmanial 6 and antitumor 5,7 activities. The antitumor and antimitotic effect may result from the phospholipase D [8][9][10] , DNA gyrase 11 or thioredoxin-reductase [12][13][14] inhibition.…”

“…However, it is assumed that a fungus living in this plant 16 produced this compound. Meanwhile, a large number of such spiro compounds were isolated mostly from endophytic fungi and named diepoxines 1 , Sch plus number 8,17,18 , CJ-plus number 11 , cladosporins [19][20][21] , palmarumycins 3,[22][23][24] , sphaerolones 25 , decaspirones 4,17 and deoxypreussomerin 26 . The interesting structures, various biological activities and potential applications in agriculture, medicine and the food industry attracted the attention of many research groups with respect to the synthesis of spirobisnaphthalenes.…”

Enhanced Production of Palmarumycins C12 and C13 in Mycelial Liquid Culture of the Endophytic Fungus <i>Berkleasmium<?i> sp. Dzf12 with <i>In situ</i> Macroporous Resin Adsorption

“…Dzf12. Palmarumycins C 12 and C 13 , which exhibit antibacterial, antifungal and anti-tumor activities as well as inhibitory activity on phospholipase D (PLD), have been isolated from other fungi such as Coniothyrium sp., Cladosporium chlorocephalum and Nattrassia mangiferae, [8][9][10][11][12]. With the aim of speeding up application of palmarumycins C 12 and C 13 , considerable efforts have been directed at seeking strategies for improving palmarumycins C 12 and C 13 production in liquid culture of Berkleasmium sp.…”