Secondary metabolites from the genus xylaria and their bioactivities.

CHEMISTRY & BIODIVERSITY – Vol. 11 (2014)

673

REVIEW Secondary Metabolites from the Genus Xylaria and Their Bioactivities by Fei Song, Shao-Hua Wu*, Ying-Zhe Zhai, Qi-Cun Xuan, and Tang Wang Key Laboratory for Microbial Resources of the Ministry of Education, Yunnan Institute of Microbiology, Yunnan University, Kunming 650091, P. R. China (phone: þ 86-871-65032423; e-mail: [email protected])

Contents 1. Introduction 2. Secondary Metabolites 2.1. Sesquiterpenoids 2.1.1. Eremophilanes 2.1.2. Eudesmanolides 2.1.3. Presilphiperfolanes 2.1.4. Guaianes 2.1.5. Brasilanes 2.1.6. Thujopsanes 2.1.7. Bisabolanes 2.1.8. Other Sesquiterpenes 2.2. Diterpenoids and Diterpene Glycosides 2.3. Triterpene Glycosides 2.4. Steroids 2.5. N-Containing Compounds 2.5.1. Cytochalasins 2.5.2. Cyclopeptides 2.5.3. Miscellaneous Compounds 2.6. Aromatic Compounds 2.6.1. Xanthones 2.6.2. Benzofuran Derivatives 2.6.3. Benzoquinones 2.6.4. Coumarins and Isocoumarins 2.6.5. Chroman Derivatives 2.6.6. Naphthalene Derivatives 2.6.7. Anthracenone Derivatives 2.6.8. Miscellaneous Phenolic Derivatives 2.7. Pyranone Derivatives 2.8. Polyketides 3. Biological Activities 3.1. Antimicrobial Activity 3.2. Antimalarial Activity 2014 Verlag Helvetica Chimica Acta AG, Zrich

674


3.3. Cytotoxic Activity 3.4. Other Activities 4. Conclusions 1. Introduction. – Xylaria Hill ex Schrank is the largest genus of the family Xylariaceae Tul. & C. Tul. (Xylariales, Sordariomycetes) and presently includes ca. 300 accepted species of stromatic pyrenomycetes [1]. Xylaria species are widespread from the temperate to the tropical zones of the earth [2]. The traditional view of Xylaria sp. as saprotrophic wood-destroyers had to be emended, since it was found that members of this genus occur ubiquitously as endophytes of vascular plant [3]. Not only Xylaria, but also the entire Xylariaceae appear to play an important ecological role, which has probably come about during their long co-evolution with seed plants [4]. Fungi of the genus Xylaria have been shown to be potential sources of novel secondary metabolites, and many of them possess biological activities relevant for drug discovery [5], including cytotoxic, antimalarial, and antimicrobial activities. In this review, we compile the most important secondary metabolites isolated from the genus Xylaria over the past few decades. The biological activities of the compounds isolated in recent years are also included. 2. Secondary Metabolites. – The secondary metabolites from Xylaria sp. include sesquiterpenoids, diterpenoids, diterpene glycosides, triterpene glycosides, steroids, Ncontaining compounds, aromatic compounds, pyrone derivatives, and polyketides. Their structures, 1 – 188 are shown below, and their names and the corresponding fungal sources are compiled in the Table (see below). 2.1. Sesquiterpenoids. A total of 46 sesquiterpenoids, 1 – 46, have been reported from Xylaria species. They possess various C-skeletons, such as eremophilanes, eudesmanolides, presilphiperfolanes, guaianes, brasilanes, thujopsanes, and bisabolanes. 2.1.1. Eremophilanes. Compounds 1 – 8 are eremophilane-type sesquiterpenes, isolated from the endophytic Xylaria sp. BCC21097 [6]. Xylarenones A and B (9 and 10, resp.) were isolated from Xylaria sp. NCY2 [7]. An eremophilane sesquiterpenoid, xylarenic acid (11), was isolated from the AcOEt extract of Xylaria sp. 101, obtained from the fruiting body collected in Gaoligong Mountain [8]. Two eremophilane sesquiterpenes, phaseolinone (12) and phomenone (13), were isolated from Xylaria sp. PA-01, obtained from the leaves of Piper aduncum [9]. Compounds 14 and 15 were isolated from the wood-decay fungus Xylaria sp. BCC5484 [10]. Singh et al. [11] isolated integric acid (16) from Xylaria sp. MF6254. Xylarenals A and B (17 and 18, resp.) were found in Xylaria persicaria, associated with the fallen fruits of Liquidambar styracifua, in eastern North America [12]. Four eremophilane sesquiterpenoids, 19 – 22, were isolated from the mangrove endophytic fungus Xylaria sp. BL321 [13]. 2.1.2. Eudesmanolides. Four 12,8-eudesmanolide sesquiterpenoid lactones, 23 – 26, were isolated from the fungus Xylaria ianthinovelutina [14]. Two 12,8-eudesmanolides, 27 and 28, were isolated from the fermentation broth of the wood-decay fungus Xylaria sp. BCC5484 [10]. 2.1.3. Presilphiperfolanes. Two presilphiperfolane sesquiterpenes, 9,15-dihydroxypresilphiperfolan-4-oic acid (29) and 15-acetoxy-9-hydroxypresilphiperfolan-4-oic acid (30), were isolated from Xylaria sp. PA-01 [9].


675

676


2.1.4. Guaianes. Two guaiane sesquiterpenoids, xylaranols A and B (31 and 32, resp.) were isolated from Xylaria sp. 101, obtained from the fruiting body collected in Gaoligong Mountain [8]. 2.1.5. Brasilanes. Xylarenic acid (33) was isolated from Xylaria sp. NCY2 [7]. 2.1.6. Thujopsanes. Three sesquiterpenes, xylcarpins A – C (34 – 36, resp.), were obtained from Xylaria carpophila [15]. 2.1.7. Bisabolanes. Two sesquiterpenes, xylcarpins D and E (37 and 38, resp.) were obtained from Xylaria carpophila [15]. 2.1.8. Other Sesquiterpenes. Xylaric acids A – D (39 – 42, resp.), hydroheptelidic acid (43), gliocladic acid (44), chlorine heptelidic acid (45), and trichoderonic acid A (46) were isolated from the fungus Xylaria sp. associated with termite nests [16]. 2.2. Diterpenoids and Diterpene Glycosides. Four pimarane-type diterpenoids, 47 – 50, and four pimarane diterpene glycosides, 51 – 54, have been reported from Xylaria species. Xylarenolide (47) was isolated from Xylaria sp. 101 [8]. Compounds 48 and 49 were isolated from the fungus Xylaria sp. BCC 5484, obtained from an unidentified dead wood in Hala Wildlife Sanctuary, Narathiwat Province, Thailand [10]. Sphaeropsidin C (50) and xylopimarane (51) were isolated from the fungus Xylaria sp. BCC 4297 [17]. 16-(a-d-Mannopyranosyloxy)isopimar-7-en-19-oic acid (52), 15-hydroxy16-(a-d-mannopyranosyloxy)isopimar-7-en-19-oic-acid (53), and 16-(a-d-glucopyranosyloxy)isopimar-7-en-19-oic acid (54) were isolated from Xylaria polymorpha [16] [18]. Sordaricin (55) was isolated from the endophytic Xylaria sp. PSU-D14 [19]. A sordaricin derivative, containing a tricyclic uronic acid moiety, 56, was isolated from the culture fluids of a wood-inhabiting Xylaria sp. [20].


677

2.3. Triterpene Glycosides. Four triterpene glycosides, kolokosides A – D (57 – 60, resp.), have been reported from the Hawaiian wood-decay fungus Xylaria sp. NRRL 4019 [21].

2.4. Steroids. Cerevisterol (61) was isolated from the wood-decay fungus Xylaria sp. BCC 9653 [22]. Ergosta-4,6,8(14),22-tetraen-3-one (63) was found in Xylaria sp. collected in Vietnam [23]. Blazein (62), ergosterin (64), and 5,8-epidioxyergosta-6,22dien-3-ol (65) were isolated from an endolichenic Xylaria sp. [24]. 2.5. N-Containing Compounds. To date, 32 N-containing compounds have been isolated from species of Xylaria. More than half of these compounds are cytochalasins, which were mainly obtained from Xylaria hypoxylon and X. obovata.

678


2.5.1. Cytochalasins. A total of 18 cytochalasins, 66 – 83, have been reported from several Xylaria species. They are the most important bioactive components in the genus Xylaria. Among them, two new closely related cytotoxic cytochalasin compounds, 19,20-epoxycytochalasin Q (66) and deacetyl 19,20-epoxycytochalasin Q (67) were isolated from Xylaria obovata ADA-288, Xylaria sp. SCSIO156, and Xylaria hypoxylon [25 – 27]. 18-Deoxy-19,20-epoxycytochalasin Q (68), deacetyl 19,20-epoxycytochalasin C (69), and 19,20-epoxycytochalasin C (70), were isolated from the fungi Xylaria obovata and Xylaria hypoxylon [2] [27]. 19,20-Epoxycytochalasin R (71), 18-deoxy19,20-epoxycytochalasin R (72), cytochalasin R (73), and 19,20-epoxycytochalasins D and E (74 and 75, resp.) were isolated from Xylaria hypoxylon, associated with a soil sample containing decayed wood chips collected at Tikal, Guatemala [27]. 18Deoxycytochalasin Q (76), 21-O-deacetylcytochalasin Q (77), and cytochalasins Q and D (78 and 79, resp.) were isolated from the marine sediment-derived fungus Xylaria sp. SCSIO156, Xylaria obovata ADA-288, Xylaria sp. BCC9653, and Xylaria hypoxylon [2] [22] [26] [27]. Deacetylcytochalasin D (80) and cytochalasin O (81) were isolated from the wood-decay fungus Xylaria sp. BCC9653 [22]. Cytochalasin B (82) was isolated from the endophytic Xylaria sp. [28]. A new cytochalasin derivative, xylarisin (83), was found in the marine-derived fungus Xylaria sp. PSU-F100 [29]. 2.5.2. Cyclopeptides. Five cyclopeptides have been reported from Xylaria sp. Cyclo(l-Pro-l-Tyr) (84) was isolated from the wood-decay fungus Xylaria sp. BCC 9653 [22]. Neoechinulin A (85) was isolated from the fruiting bodies of Xylaria euglossa [30]. A cyclic peptide containing an allenic ether of a N-(p-hydroxycinnamoyl) amide, xyloallenolide A (86), was isolated from Xylaria sp. No. 2508 [31]. Two cyclic pentapeptides, 87 and 88, were isolated from the crude extract of an endolichenic fungus Xylaria sp. [24]. 2.5.3. Miscellaneous Compounds. Uracil (89) was isolated from Xylaria sp. BCC 9653 [22]. A methyl p-aminobenzoate derivative, 90, quinoline-4-carbonitrile (91), and


679

quinoline-4-carboxaldehyde oxime (92) were isolated from the wood-decay fungus Xylaria sp. BCC 9653 [22]. Xylaramide (93) was isolated from the wood-inhabiting fungus Xylaria longipes [32]. ()-Xylariamide A (94) was isolated from Xylaria sp.

680


FRR5657, obtained from the damp white rice under static conditions [33]. 10Hydroxycamptothecin (95) was isolated from the endophytic Xylaria sp. M20, associated with Camptotheca acuminata [34]. Xylactam (96) and penochalasin B2 (97), were isolated from the fruiting bodies of Xylaria euglossa [30].

2.6. Aromatic Compounds. So far, 60 aromatic compounds, 98 – 157, have been isolated from the genus Xylaria. This group includes various types of compounds, such as xanthones, benzofurans, benzoquinones, isocoumarins, chromans, naphthalenes, anthracenones, and some miscellaneous phenolic derivatives. As can be seen from the Formulae, about one third of all reported compounds from Xylaria contain phenyl group. 2.6.1. Xanthones. Four xanthones, 98 – 101, were obtained from the endophytic fungus Xylaria sp. FRR5657 [35] [36]. 2.6.2. Benzofuran Derivatives. Xyloester A (102), xyloallenolide B (103), and a dihydrobenzofuran, 104, were isolated from the mangrove endophytic fungus Xylaria sp. No. 2508 [37]. Xylaral (105) was isolated from Xylaria polymorpha [38]. 7Dechlorogriseofulvin (106) and griseofulvin (107) were found in the endophyic fungus Xylaria sp. [28]. 2.6.3. Benzoquinones. 2-Hydroxy-3-methoxy-5-methyl-1,4-benzoquinone (108) was isolated from the fruiting body of fungal strain Xylaria sp. 101 [39]. Three benzoquinone derivatives, 109 – 111, were isolated from an endophytic fungus Xylaria sp. [40]. (4S,5S,6S)-5,6-Epoxy-4-hydroxy-3-methoxy-5-methylcyclohexen-1-one (112) was isolated from Xylaria carpophila [15]. 2.6.4. Coumarins and Isocoumarins. 7-Amino-4-methylcoumarin (113) was isolated from the endophytic Xylaria sp. YX-28 [41]. 5-Carboxymellein (114) was found in


681

682


Xylaria sp. associated with termite nests [16]. Three mellein derivatives, 5-carboxymellein (114), mellein methyl ether (115), and 5-hydroxymellein (116), were isolated from the wood-decay fungus Xylaria sp. BCC9653 [22]. Compounds 114, 115, and 117 were obtained from the marine-derived fungus Xylaria sp. PSU-F100 [29]. 4Hydroxymellein (118) was isolated from an endophytic fungus Xylaria sp. [40]. The dihydroisocoumarin, 119, was isolated from Xylaria sp., a fungus associated with Piper aduncum (Piperaceae) [42]. 2.6.5. Chroman Derivatives. 2,3-Dihydro-5-hydroxy-2-methyl-4H-1-benzopyran-4one (120) was isolated from the endophytic fungus Xylaria sp. PSU-D14 [19]. Eight unique metabolites, xyloketals A – H and J (121 – 128 and 129, resp.) were isolated from mangrove fungus Xylaria sp. (No. 2508), obtained from the South China Sea [37] [43 – 46]. 2.6.6. Naphthalene Derivatives. Two tetralone derivatives, xylariols A and B (130 and 131, resp.) were isolated from Xylaria hypoxylon AT-028, obtained from the fresh stems of Ligustrum lucidum [47]. A tetralone, 3,4-dihydronaphthalen-1(2H)-one (132) and naphthalen-1,8-diol 1-O-d-glucopyranoside (133) were isolated from the solid culture of the Xylaria sp. associated with termite nest [16]. 2.6.7. Anthracenone Derivatives. Three phlegmacin type pigments, (S)-torosachrysone-8-O-methyl ether (134), emodin-6,8-di-O-methyl ether (135), and phlegmacin A 8,8’-di-O-methyl ether (136) were isolated from Xylaria euglossa [48]. 2.6.8. Miscellaneous Phenolic Derivatives. Tyrosol (137) was isolated from the wood-inhabiting ascomycete Xylaria longipes [33]. Compound 138 was isolated from mangrove fungus Xylaria sp. No. 2508 [43]. Coloration B (139) was obtained from Xylaria intracolorata [49]. Xylarosides A and B (140 and 141, resp.) were reported from the endophytic fungus Xylaria sp. PSU-D14 [19]. Xylarinols A and B (142 and 143, resp.) were found in the fruiting bodies of Xylaria polymorpha [50]. Globoscin (144) and globoscinic acid (145) were found in Xylaria globosa [51]. Maldoxone (146), maldoxin (147), dihydromaldoxin (148), isodihydromaldoxin (149), and dechlorodihydromaldoxin (150) were isolated from Xylaria sp. [52]. Two aromatic allenic ethers, 151 and 152, were isolated from the fungus Xylaria sp. No. 2508, obtained from the seed of an angiosperm tree from the South China Sea Coast [31]. Four further aromatic allenic ethers, 153 – 156, were isolated from the fungus Xylaria sp. No. 2508 [53]. Methyl (E)-3-(4-methoxyphenoxy)propenoate (157) was isolated from the woodinhabiting tropical fungus Xylaria obovata ADA-288 [2]. 2.7. Pyranone Derivatives. A new g-pyrone, grammicin (158), was isolated from the fungus Xylaria grammica [54]. Xylaropyrone (159) was isolated from the endophytic Xylaria feejeensis MU 18 [55]. Two a-pyrones, 160 and 161, were isolated from the endophytic fungus Xylaria sp. [56]. Xylariolide D (162) and one taiwapyrone (163) were isolated from the endophytic fungus Xylaria sp. NCY2 [57]. Xylarone (164) and 8,9-dehydroxylarone (165) were isolated from Xylaria hypoxylon [58]. One pyrone derivative 166 was isolated from the marine-derived fungus Xylaria sp. PSU-F100 [29]. Coloratin A (167) was isolated from the Vietnamese inedible mushroom Xylaria intracolorata [49]. 2.8. Polyketides. Xylarioic acid B (168), xylariolides A – C (169 – 171, resp.), and methyl xylariate C (172) were isolated from the endophytic fungus Xylaria sp. NCY2 [57]. Three polysubstituted fatty acids, malaysic acid (173), berteric acid (174), and


683

cameronic acid (175) were obtained from species of the fungal genus Xylaria [59]. 2,3Didehydrotelfairic anhydride (176) and two telfairic acids, 177 and 178, were isolated from the fungus Xylaria telfairii [60]. Piliformic acid (179), also known as 2-hexylidene-

684



685

Table 1. Secondary Metabolites from the Genus Xylaria No. Compound class and name

Source

Ref.

Eremophilanes 1 1b,7a-Trihydroxyeremophil-11(13)-en-12,8b-olide 2 7a,10a-Dihydroxy-1b-methoxyeremophil-11(13) en-12,8b-olide 3 1a,10a-Epoxy-7a-hydroxyeremophil-11(13)-en-12,8b-olide 4 1b,10a,13-Trihydroxyeremophil-7(11)-en-12,8b-olide 5 10a,13-Diphydroxy-1b-methoxyeremophil-7(11)-en-12,8b-olide 6 Mairetolide F 7 1a,10a-Epoxy-13-hydroxyeremophil-7(11)-en-12,8b-olide 8 1a,10a-Epoxy-3a-hydroxyeremophil-7(11)-en-12,8b-olide 9 Xylarenone A 10 Xylarenone B 11 Xylarenic acid 12 Phaseolinone 13 Phomenone 14 Eremophila-9,11(13)-diene-7b,8a,12-triol 15 Phomadecalin E 16 Integric acid 17 Xylarenal A 18 Xylarenal B 19 6’-Demethyl 07 H239-A 20 6’-Demethyl-4’-methyl 07 H239-A 21 07 H239-A 22 8’,9’-Didemethyl-2’,7’-dimethyl 07 H239-A

X. sp. BCC21097 X. sp. BCC21097 X. sp. BCC21097 X. sp. BCC21097 X. sp. BCC21097 X. sp. BCC21097 X. sp. BCC21097 X. sp. BCC21097 X. sp. NCY2 X. sp. NCY2 X. sp. 101 X. sp. PA-01 X. sp. PA-01 X. sp. BCC5484 X. sp. BCC5484 X. sp. MF 6254 X. persicaria X. persicaria X. sp. BL321 X. sp. BL321 X. sp. BL321 X. sp. BL321

[6] [6] [6] [6] [6] [6] [6] [6] [7] [7] [8] [9] [9] [10] [10] [11] [12] [12] [13] [13] [13] [13]

Eudesmanolides 23 3a,4a,7b-Trihydroxyeudesm-11(13)-en-12,8-olide 24 4a,7b-Dihydroxy-3a-methoxyeudesm-11(13)-en-12,8-olide 25 7b-Hydroxyeudesma-3,11(13)-dien-12,8-olide 26 13-Hydroxyeudesma-3,7(11)-dien-12,8-olide 27 3a,4-Epoxy-13-hydroxyeudesm-7(11)-en-12,8a-olide 28 3a,4-Epoxyeudesm-7(11)-en-12,8a-olide

X. ianthinovelutina X. ianthinovelutina X. ianthinovelutina X. ianthinovelutina X. sp. BCC5484 X. sp. BCC5484

[14] [14] [14] [14] [10] [10]

Presilphiperfolanes 29 9,15-Dihydroxypresilphiperfolan-4-oic acid 30 15-Acetoxy-9-hydroxypresilphiperfolan-4-oic acid

X. sp. PA-01 X. sp. PA-01

[9] [9]

Guaianes 31 Xylaranol A 32 Xylaranol B

X. sp. 101 X. sp. 101

[8] [8]

Brasilanes 33 Xylarenic acid

X. sp. NCY2

[7]

Thujopsanes 34 Xylcarpin A 35 Xylcarpin B 36 Xylcarpin C

X. carpophila X. carpophila X. carpophila

[15] [15] [15]

Bisabolanes 37 Xylcarpin D 38 Xylcarpin E

X. carpophila X. carpophila

[15] [15]

Other sesquiterpenes 39 Xylaric acid A

X. sp.

[16]

686


Table 1 (cont.) No. Compound class and name

Source

Ref.

X. sp. X. sp. X. sp. X. sp. X. sp. X. sp. X. sp.

[16] [16] [16] [16] [16] [16] [16]

Diterpenoids and diterpene glycosides 47 Xylarenolide 48 9-Deoxy-14a-hydroxyhymatoxin E 49 Hymatoxin E 50 Sphaeropsidin C 51 Xylopimarane 52 16-(a-d-Mannopyranosyloxy)isopimar-7-en-19-oic acid 53 15-Hydroxy-16-(a-d-mannopyranosyloxy)isopimar-7-en-19-oic-acid 54 16-(a-d-Glucopyranosyloxy)isopimar-7-en-19-oic acid 55 Sordaricin 56 Xylarin

X. sp. 101 X. sp. BCC5484 X. sp. BCC5484 X. sp. BCC4297 X. sp. BCC4297 X. polymorpha X. polymorpha X. polymorpha X. sp. PSU-D14 X. sp. A19 – 91

[8] [10] [10] [17] [17] [16] [18] [18] [16] [18] [19] [20]

Triterpene Glycosides 57 Kolokoside A 58 Kolokoside B 59 Kolokoside C 60 Kolokoside D

X. sp. NRRL40192 X. sp. NRRL40192 X. sp. NRRL40192 X. sp. NRRL40192

[21] [21] [21] [21]

Steroids 61 Cerevisterol 62 Blazein 63 Ergosta-4,6,8(14),22-tetraen-3-one 64 Ergosterin 65 5,8-Epidioxyergosta-6,22-dien-3-ol

X. sp. BCC9653 X. sp. 7S-1 – 3-1 X. sp. X. sp. 7S-1 – 3-1 X. sp. 7S-1 – 3-1

[22] [24] [23] [24] [24]

X. obovata X. sp. SCSIO 156 X. hypoxylon X. obovata X. sp. SCSIO 156 X. hypoxylon X. obovata X. hypoxylon X. obovata X. obovata X. hypoxylon X. hypoxylon X. hypoxylon X. hypoxylon X. hypoxylon X. hypoxylon X. sp. SCSIO 156 X. sp. SCSIO 156

[25] [26] [27] [25] [26] [27] [2] [27] [2] [2] [27] [27] [27] [27] [27] [27] [26] [26]

40 41 42 43 44 45 46

Xylaric acid B Xylaric acid C Xylaric acid D Hydroheptelidic acid Gliocladic acid Chlorine heptelidic acid Trichoderonic acid A

Cytochalasins 66 19,20-Epoxycytochalasin Q

67 Deacetyl-19,20-epoxycytochalasin Q

68 18-Deoxy-19,20-epoxycytochalasin Q 69 Deacetyl-19,20-epoxycytochalasin C 70 19,20-Epoxycytochalasin C 71 72 73 74 75 76 77

19,20-Epoxycytochalasin R 18-Deoxy-19,20-epoxycytochalasin R Cytochalasin R 19,20-Epoxycytochalasin D 19,20-Epoxycytochalasin N 18-Deoxycytochalasin Q 21-O-Deacetylcytochalasin Q


687


Source

Ref.

78 Cytochalasin Q

X. obovata X. sp. SCSIO 156 X. hypoxylon X. sp. BCC 9653 X. sp. SCSIO 156 X. sp. BCC9653 X. sp. BCC9653 X. sp. X. sp. PSU-100

[2] [26] [27] [22] [26] [22] [22] [28] [29]

88 Cyclo(l-Val-d-Ile-l-Leu-l-Pro-d-Leu)

X. sp. BCC9653 X. euglossa X. sp. No.2508 X. sp. No.7S-1 – 3-1 X. carpophila X. sp. No.7S-1 – 3-1

[22] [30] [31] [24] [15] [24]

Miscellaneous N-containing compounds 89 Uracil 90 Methyl 4-amino-2-(2,3-dihydroxy-3-methylbutyl)benzoate 91 Quinoline-4-carbonitrile 92 Quinoline-4-carboxaldehyde oxime 93 Xylaramide 94 ()-Xylariamide A 95 10-Hydroxycamptothecin 96 Xylactam 97 Penochalasin B2

X. sp. BCC 9653 X. sp. BCC 9653 X. sp. BCC 9653 X. sp. BCC 9653 X. longipes X. sp. FRR5657 X. sp. M 20 X. euglossa X. euglossa

[22] [22] [22] [22] [32] [33] [34] [30] [30]

X. sp. FRR5657 X. sp. FRR5657

[35] [35]

X. sp. FRR5657 X. sp. FRR5657

[36] [36]

X. sp. No. 2508 X. sp. No. 2508 X. sp. No. 2508 X. polymorpha X. sp. X. sp.

[37] [37] [37] [38] [28] [28]

X. sp. 101 X. sp. PB-30 X. sp. PB-30 X. sp. PB-30 X. carpophila

[39] [40] [40] [40] [15]

79 Cytochalasin D 80 81 82 83

Deacetylcytochalasin D Cytochalasin O Cytochalasin B Xylarisin

Cyclopeptides 84 Cyclo(l-Pro-l-Tyr) 85 Neoechinulin A 86 Xyloallenolide A 87 Cyclo(N-methyl-l-Phe-l-Val-d-Ile-l-Leu-l-Pro)

Xanthones 98 2-Hydroxy-6-methoxy-9-oxo-9H-xanthene-1-carboxylic acid 99 2-Hydroxy-6-(hydroxymethyl)-8-methoxy-9-oxo-9H-xanthene1-carboxylic acid 100 7-Hydroxy-3-(hydroxymethyl)-1-methoxy-9H-xanthene-9-one 101 2,5-Dihydroxy-8-methoxy-6-methyl-9-oxo-9H-xanthene1-carboxylic acid Benzofuran derivatives 102 Xyloester A 103 Xyloallenolide B 104 (2-Isopropenyl-2,3-dihydrobenzofuran-5-yl)methanol 105 Xylaral 106 7-Dechlorogriseofulvin 107 Griseofulvin Benzoquinones 108 2-Hydroxy-3-methoxy-5-methyl-1,4-benzoquinone 109 2-Chloro-5-methoxy-3-methylcyclohexa-2,5-diene-1,4-dione 110 2-Hydroxy-5-methoxy-3-methylcyclohexa-2,5-diene-1,4-dione 111 Xylariaquinone A 112 (4S,5S,6S )-5,6-Epoxy-4-hydroxy-3-methoxy5-methylcyclohexen-1-one

688



Source

Ref.

X. sp. YX-28 X. sp. X. sp. BCC 9653 X. sp. PSU-F100 X. sp. BCC 9653 X. sp. PSU-F100 X. sp. PSU-F100 X. sp. PB-30 X. sp. PA-01

[41] [16] [22] [29] [22] [29] [29] [40] [42]

Chroman derivatives 120 2,3-Dihydro-5-hydroxy-2-methyl-4H-1-benzopyran-4-one 121 Xyloketal A 122 Xyloketal B 123 Xyloketal C 124 Xyloketal D 125 Xyloketal E 126 Xyloketal F 127 Xyloketal G 128 Xyloketal H 129 Xyloketal J

X. sp. PSU-D14 X. sp. No. 2508 X. sp. No. 2508 X. sp. No. 2508 X. sp. No. 2508 X. sp. No. 2508 X. sp. No. 2508 X. sp. No. 2508 X. sp. No. 2508 X. sp. No. 2508

[19] [43] [43] [43] [43] [43] [44] [45] [46] [37]

Naphthalene derivatives 130 Xylariol A 131 Xylariol B 132 3,4,5-Trihydroxy-3,4-dihydro-2H-naphthalen-1-one 133 Naphthalen-1,8-diol 1-O-d-glucopyranoside

X. hypoxylon X. hypoxylon X. sp. X. sp.

[47] [47] [16] [16]

Anthracenone derivatives 134 ( S )-Torosachrysone 8-O-methyl ether 135 Emodin 6,8-di-O-methyl ether 136 Phlegmacin A 8,8’-di-O-methyl ether

X. euglossa X. euglossa X. euglossa

[48] [48] [48]

Miscellaneous phenolic derivatives 137 Tyrosol 138 1-(2,4-Dihydroxyphenyl)ethanone 139 Coloration B 140 Xylaroside A 141 Xylaroside B 142 Xylarinol A 143 Xylarinol B 144 Globoscin 145 Globoscinic acid 146 Maldoxone 147 Maldoxin 148 Dihydromaldoxin 149 Isodihydromaldoxin 150 Dechlorodihydromaldoxin 151 3-[4-(Buta-2,3-dienyloxy)phenyl]acrylic acid 152 Eucalyptene

X. longipes X. sp. No. 2508 X. intracolorata X. sp. PSU-D14 X. sp. PSU-D14 X. polymorpha X. polymorpha X. globosa X. globosa X. sp. X. sp. X. sp. X. sp. X. sp. X. sp. No. 2508 X. sp. No. 2508

[32] [43] [49] [19] [19] [50] [50] [51] [51] [52] [52] [52] [52] [52] [31] [31]

Coumarins and isocoumarins 113 7-Amino-4-methylcoumarin 114 5-Carboxymellein 115 Mellein methyl ether 116 5-Hydroxymellein 117 5-( Hydroxymethyl)mellein 118 4-Hydroxymellein 119 (3R,4R )-3,4-Dihydro-4,6-dihydroxy-3-methyl-1-oxo1H-isochromene-5-carboxylic acid


689


Source

Ref.

153 (7E )-3-[4-(Buta-2,3-dienyloxy)-3-methoxyphenyl]acrylic acid 154 Methyl (7E)-3-{4-[4-(Buta-2,3-dienyloxy)benzyloxy]phenyl}acrylate 155 Methyl (7E)-3-{4-[4-(Buta-2,3-dienyloxy)benzyloxy]-3-methoxyphenyl}acrylate 156 Methyl 4-[4-( Buta-2,3-dienyloxy)benzyloxy]benzoate 157 Methyl ( E )-3-(4-methoxyphenoxy)propenoate

X. sp. No. 2508 X. sp. No. 2508 X. sp. No. 2508

[53] [53] [53]

X. sp. No. 2508 X. obovata

[53] [2]

Pyrone derivatives 158 Grammicin 159 Xylaropyrone 160 (þ)-Phomalactone 161 3,4,5,6-Tetrahydro-5-hydroxy-6-(prop-1-enyl)-4H-pyran-2-one 162 Xylariolide D 163 5-(1-Hydroxybutyl)-6-(hydroxymethyl)-2H-pyran-2-one 164 Xylarone 165 8,9-Dehydroxylarone 166 6-[(1R )-1-Hydroxypentyl]-4-methoxy-2H-pyran-2-one 167 Coloratin A

X. grammica X. feejeensis X. sp. 300A7 – 2 X. sp. 300A7 – 2 X. sp. NCY2 X. sp. NCY2 X. hypoxylon X. hypoxylon X. sp. PSU-F100 X. intracolorata

[54] [55] [56] [56] [57] [57] [58] [58] [29] [49]

Polyketides 168 Xylarioic acid B 169 Xylariolide A 170 Xylariolide B 171 Xylariolide C 172 Methyl xylariate C 173 Malaysic acid 174 Berteric acid 175 Cameronic acid 176 2,3-Didehydrotelfairic anhydride 177 threo-Telfairic acid 178 erythro-Telfairic acid 179 Piliformic acid 180 (2E,4S )-2,4-Dimethyloct-2-enoic acid 181 Xylarinic acid A 182 Xylarinic acid B 183 Multiplide A 184 Multiplide B 185 Xylarolide 186 Clonostochydiol 187 Xylobovide 188 (3S,3aS,6R,6aR )-Dihydrosporothrioride

X. sp. NCY 2 X. sp. NCY 2 X. sp. NCY 2 X. sp. NCY 2 X. sp. NCY 2 X. sp. X. sp. X. sp. X. telfairii X. telfairii X. telfairii X. sp. PSU-100 X. sp. PSU-100 X. polymorpha X. polymorpha X. multiplex X. multiplex X. sp. 101 X. obovata X. obovata X. sp. BCC21097

[57] [57] [57] [57] [57] [59] [59] [59] [60] [60] [60] [28] [29] [29] [61] [61] [62] [62] [39] [2] [2] [6]

3-methylbutanedioic acid, was obtained from an endophytic fungus isolated from Palicourea marcgravii [28]. Two carboxylic acids, 179 and 180, were isolated from the marine-derived fungus Xylaria sp. PSU-F100 [29]. Two polypropionates, named xylarinic acids A and B (181 and 182, resp.) were isolated from the fruiting body of Xylaria polymorpha [61]. Two ten-membered lactones, multiplides A and B (183 and 184, resp.) were obtained from Xylaria multiplex BCC1111 [62]. One novel nonenolide, xylarolide (185), was isolated from the fruiting body of fungal strain Xylaria sp. 101

690


[39]. Clonostochydiol (186) and xylobovide (187) were obtained from the woodinhabiting tropical fungus Xylaria obovata ADA-288 [2]. A furofurandione, 188, was isolated from the endophytic fungus Xylaria sp. BCC 21097 [6]. 3. Biological Activities. – The secondary metabolites from genus Xylaria possess various biological properties, which were mainly antimicrobial, antimalarial, and cytotoxic activities. Further biological features include antiobesity, acetylcholine esterase inhibitory, l-calcium channel blocking, and anti-HSV-1 activities. 3.1. Antimicrobial Activity. An eremophilane-type sesquiterpene, 3, exhibited activity against Candida albicans with an IC50 value of 7.8 mm [6]. Xylarenones A and B (9 and 10, resp.), and xylarenic acid (33) inhibited the growth of bacteria, but had no effect on the growth of yeasts at a concentration of 50 mg/ml [7]. Phomenone (13) exhibited antifungal activity at a detection limit of 10.0 mg, comparable with the same amount of the standard nystatin [9]. Xylopimarane (51) exhibited antibacterial activities against Bacillus subtilis (ATCC 6051) and Staphylococcus aureus (ATCC 29213) in standard agar disk-diffusion assays at 200 mg/disk [21]. Sordaricin (55) displayed the best antifungal activity against C. albicans with an MIC value of 32 mg/ml, but it was much less active than amphotericin B (MIC 0.25 mg/ml) [19]. Xylarin (56) showed high activities towards yeasts, the most sensitive strains were Nematospora coryli and Saccharomyces cerevisiae [20]. Compounds 83, 114, 115, 117, 166, 179, and 180, showed mild antibacterial activities against standard S. aureus ATCC 25923 and methicillin-resistant strain [29]. A cyclic pentapeptide, 87, showed strong synergistic antifungal activity against C. albicans SC5314 with 0.004 mg/ml of ketoconazole [24]. 7Amino-4-methylcoumarin (113) exhibited strong inhibitory activities against tested microorganisms, including S. aureus, Escherichia coli, Salmonella typhia, Salmonella typhimurium, Salmonella enteritidis, Aeromonas hydrophila, Yersinia sp., Vibrio anguillarum, Shigella sp., Vibrio parahaemolyticus, C. albicans, Penicillium expansum, and Aspergillus niger. It was particularly effective against Aeromonas hydrophila with an MIC value of 4 mg/ml [41]. Coloratin A (167) showed strong antimicrobial activity [49]. Compounds 162, 163, and 168 – 172 inhibited the growth of pathogenic bacteria E. coli ATCC 25922, B. subtilis ATCC 9372, and S. aureus ATCC25923 with MIC values above 10 mg/ml, but they had no effects on the growth of yeasts Saccharomyces cerevisiae ATCC9763 and C. albicans As 2.538 at a concentration of 10 mg/ml [57]. Xylarinic acids A and B (181 and 182, resp.) displayed significant antifungal activities against plant pathogenic fungi Pythium ultinum, Magnaporthe grisea, A. niger, Alternaria panax, and Fusarium oxysporium [61]. Multiplides A and B (183 and 184, resp.) exhibited antifungal activities against C. albicans with IC50 values of 7 and 2 mg/ ml, respectively [62]. 3.2. Antimalarial Activity. Compounds 2 and 3 displayed antimalarial activities against Plasmodium falciparum K1 with IC50 values of 8.1 and 13 mm, respectively [6]. A eudesmanolide sesquiterpenoid lactone, 25, exhibited biological activity against P. falciparum K1 strain with an IC50 value of 2.71 mg/ml [14]. Compounds 109 and 112 showed in vitro activities against P. falciparum K1 strain with IC50 values of 1.84 and 6.68 mm [40], respectively. Two lactones, 116 and 160, showed weak antiplasmodial activities when tested against a chloroquine-resistant strain of P. falciparum with IC50 values of 19 and 13 mg/ml, respectively [56].


691

3.3. Cytotoxic Activity. Eremophilanolides possessing an a-methylidene-g-lactone moiety, 1 – 3, exhibited moderate cytotoxic activities against cancer cell lines KB, MCF7, and NCI-H187, and nonmalignant Vero cells in the range of IC50 3.8 – 21 mm [6]. Phaseolinone (12) showed 20 – 50% of cytotoxicity in CHO cell line at 20 – 200 mm, respectively, when compared to the DMSO-treated cells [9]. Compounds 9, 10, and 33 exhibited moderate antitumor activities against HeLa cells [7]. Three 12,8-eudesmanolide sesquiterpenoid lactones, 23, 24, and 26, exhibited activities against NCI-H187, KB, and MCF-7 cell lines with IC50 values varying in the range of 0.78 – 19.15 mg/ml [14]. Chlorine heptelidic acid (45) showed slight cytotoxicities against two cell lines, A549 and SGC7901 [16]. Xylopimarane (51) exhibited cytotoxicity against cancer cell lines KB, MCF-7, and NCI-H187 with IC50 values of 1.0, 13, and 65 mm, respectively [17]. The diterpene glycosides 52 – 54 showed cytotoxicities against human cancer cell lines HL60, K562, HeLa, and LNCaP with IC50 values ranging from 71 to 607 mm [18]. Xylarin (56) showed weak cytotoxicities against HL60 and L1210, but not against HeLa S3 and BHK 21 cell lines [20]. 19,20-Epoxycytochalasin Q (66) and deacetyl 19,20epoxycytochalasin Q (67) were lethal to brine shrimp with an IC50 value of 2.5 mg/ml and cytotoxic to HL-60 cell line at 1 mg/ml. They also inhibited mammalian cell growth with high potency as demonstrated in the Vero monkey cell-growth inhibition (XTT) assay for cytotoxicity with IC50 values of 0.46 for 66 and 1.9 mg/ml for 67 [25]. Compounds 66, 67, and 76 – 79 showed cytotoxic activities against the MCF-7, SF-268, and NCI-H 460 cell lines with IC50 values varying between 14.4 and 96.4 mm [26]. ()Xylariamide A (94) was 0 and 71% lethal to brine shrimp at 20 and 200 mg/ml, respectively [33]. Penchalasin B2 (97) showed potent cytotoxicity against cultured P388 cell [63]. Xylariaquinone A (111) showed weak cytotoxicity against four of the tests cell lines, HL-60, SMMC-7721, A-549, and MCF-7 [15]. Two benzoquinones derivatives, 109 and 112, were tested on African green monkey kidney fibroblasts (Vero cells) and provided IC50 values of 1.35 and > 184 mm, respectively [40]. The lactones 116, 160, and 161 showed cytotoxicities against Vero cells with IC50 values in the range of 12 – 38 mg/ml [56]. Compounds 130 and 131 showed moderate cytotoxic activities against Hep G2 cell in the in vitro cytotoxic assay with IC50 values of 22.3 and 21.2 mg/ ml, respectively [47]. Xylarone (164) reduced proliferation of Colo-320 and L1210 cells with IC50 values of 40 and 50 mg/ml, respectively, and 8,9-dehydroxylarone (165) was slightly more active with IC50 values of 25 mg/ml against Colo-320 and L1210 cells, respectively [58]. 3.4. Other Activities. A novel eremohpilane sesquiterpenoid, 16, inhibited 3’-end processing, strand transfer, and disintegration reactions catalyzed by HIV-1 integrase with IC50 values in the range of 3 – 10 mm [11]. Two eremophilane sesquiterpenoids, 17 and 18, bind selectively to the neuropeptide Y (NPY) 5 receptor but had only modest affinity. Antagonists of NPY receptor activation could have potential for development as anti-obesity drugs [12]. Compound 19 showed activation on a-glucosidase at 0.15 mm (146%), and, then, gradually produced inhibitory activity on a-glucosidase with increasing concentration with an IC50 value of 6.54 mm [13]. Compound 63 showed potential inhibitory activity of nitric oxide (NO) production in RAW 264.7 cells stimulated by lipopolysaccharide with an IC50 value of 28.96 mm [23]. A dihydroisocoumarin, 119, displayed moderate acetylcholine esterase (AChE) inhibitory activity, exhibiting a detection limit of 3.0 mg on TLC [42]. Xyloketal A (121) inhibited

692


acetylcholine esterase at a concentration of 1.5 10 6 mol/l [43]. Xyloketal F (126) had a stong l-calcium channel blocking activity [44]. Compound 133 exhibited anti-HSV-1 activity with an IC50 value of 8.4 mg/ml [5]. Xylobovide (187) is a phytotoxin inhibiting the germination of Eragrostis tef seeds at a concentration of 50 – 100 mg/ml [2]. 4. Conclusions. – Secondary metabolites from Xylaria species possess a variety of Cskeletons, and most of them exhibit biological activities. Sesquiterpenes and Ncontaining compounds are the main chemical constituents of this genus. To date, 46 sesquiterpenes of eight different subclasses have been identified. They showed a wide range of biological activities. Among them, 22 eremophilanes, as the major type of sesquiterpenes, were obtained from eight different Xylaria strains, of which only one was identified as X. persicaria at the species level. A total of 32 N-containing compounds have been isolated. Most of them are cytotoxic cytochalasins, mainly isolated from X. obovata and X. hypoxylon. Based on our literature survey, 60 substances are aromatic compounds, including various types, such as xanthones, benzofurans, benzoquinones, isocoumarins, chromans, naphthalenes, anthracenones, and miscellaneous phenolic derivatives. Xylaria has been shown to be a highly creative genus with structurally diverse and physiologically active fungal metabolites. In the future, further phytochemical and biological studies should be conducted to exploit the potential of this genus for the discovery of further bioactive natural products. It must be noted that most of the producing strains are only recognized at generic level. Among all of the related strains, there are only 15 species determined. It is reported that Xylaria species are difficult to identify and classify for a few reasons [64]. In this context, some secondary metabolites may be possibly used as markers for taxonomic identification at the species level. This work was financially supported by the National Natural Science Foundation of China (21062027, 20772105, and 20502021), the Natural Science Foundation of Yunnan Province (2010CD009), the Young Academic and Technical Leader Raising Foundation of Yunnan Province (2008PY028), and the Science Research Foundation of Yunnan Province Education Department (2010Z054).

REFERENCES [1] P. M. Kirk, P. F. Cannon, D. W. Minter, J. A. Stalpers, Ainsworth & Bisbys Dictionary of the Fungi, 10th edn., CABI Publishing, Wallingford, 2008. [2] D. Abate, W. R. Abraham, H. Meyer, Phytochemistry 1997, 44, 1443. [3] O. Petrini, L. E. Petrini, K. Rodrigues, Fitopatol Bras. 1995, 20, 531. [4] J. Fournier, F. Flessa, D. Persoh, M. Stadler, Mycol. Progr. 2011, 10, 33. [5] P. Pittayakhajonwut, R. Suvannakad, S. Thienhirun, S. Prabpai, P. Kongsaeree, M. Tanticharoen, Tetrahedron Lett. 2005, 46, 1341. [6] M. Isaka, P. Chinthanom, T. Boonruangprapa, N. Rungjindamai, U. Pinruan, J. Nat. Prod. 2010, 73, 683. [7] Z. Y. Hu, Y. Y. Li, Y. J. Huang, W. J. Su, Y. M. Shen, Helv. Chim. Acta 2008, 91, 46. [8] Y. Y. Li, Z. Y. Hu, C. H. Lu, Y. M. Shen, Helv. Chim. Acta 2010, 93, 796. [9] G. H. Silva, C. M. Oliveira, H. L. Teles, P. M. Pauletti, I. Castro-Gamboa, D. H. S. Silva, V. S. Bolzani, M. C. M. Young, C. M. Costa-Neto, L. H. Pfenning, R. G. S. Berlinck, A. R. Araujo, Phytochemistry Lett. 2010, 3, 164. [10] M. Isaka, U. Srisanoh, M. Sappan, S. Kongthong, P. Srikitikulchai, Phytochemistry Lett. 2012, 5, 78.


693

[11] S. B. Singh, D. Zink, J. Polishook, D. Valentino, A. Shafiee, K. Silverman, P. Felock, A. Teran, D. Vilella, D. J. Hazuda, R. B. Lingham, Tetrahedron Lett. 1999, 40, 8775. [12] C. J. Smith, N. R. Morin, G. F. Bills, A. W. Dombrowski, G. M. Salituro, S. K. Smith, A. Zhao, D. J. Macneil, J. Org. Chem. 2002, 67, 5001. [13] Y. Song, J. Wang, H. Huang, L. Ma, Y. Gu, L. Liu, Y. Lin, Mar. Drugs 2012, 10, 340. [14] P. Pittayakhajonwut, A. Usuwan, C. Intraudom, S. Veeranondha, P. Srikitikulchai, Planta Med. 2009, 75, 1431. [15] X. Yin, T. Feng, Z. H. Li, J. Su, Y. Li, N. H. Tan, J. K. Liu, Nat. Prod. Bioprospect. 2011, 1, 75. [16] S. Yan, S. Li, W. Wu, F. Zhao, L. Bao, R. Ding, H. Gao, H. A. Wen, F. Song, H. W. Liu, Chem. Biodiversity 2011, 8, 1689. [17] M. Isaka, A. Yangchum, P. Auncharoen, K. Srichomthong, P. Srikitikulchai, J. Nat. Prod. 2011, 74, 300. [18] Y. Shiono, S. Motoki, T. Koseki, T. Murayama, M. Tojima, K. Kimura, Phytochemistry 2009, 70, 935. [19] W. Pongcharoen, V. Rukachaisirikul, S. Phongpaichit, T. Kuhn, M. Pelzing, J. Sakayaroj, W. C. Taylor, Phytochemistry 2008, 69, 1900. [20] G. Schneider, H. Anke, O. Sterner, Nat. Prod. Lett. 1995, 7, 309. [21] S. T. Deyrup, J. B. Gloer, K. O. Donnell, D. T. Wicklow, J. Nat. Prod. 2007, 70, 378. [22] W. Pongcharoen, V. Rukachaisirikul, M. Isaka, K. Sriklung, Chem. Pharm. Bull. 2007, 55, 1647. [23] D. N. Quang, D. D. Bach, Nat. Prod. Res. 2008, 22, 901. [24] W. Wu, H. Dai, L. Bao, B. Ren, J. Lu, Y. Luo, L. Guo, L. Zhang, H. Liu, J. Nat. Prod. 2011, 74, 1303. [25] E. Dagne, A. A. L. Gunatilaka, S. Asmellash, D. Abate, D. G. I. Kingston, G. A. Hofmann, R. K. Johnson, Tetrahedron 1994, 50, 5615. [26] Z. Chen, H. Huang, Y. Chen, Z. Wang, J. Ma, B. Wang, W. Zhang, C. Zhang, J. Ju, Helv. Chim. Acta 2011, 94, 1671. [27] A. Espada, A. Rivera-Sagredo, J. M. Fuente, J. A. Hueso-Rodriguez, S. W. Elson, Tetrahedron 1997, 53, 6485. ˆ . R. Arau´jo, M. C. M. Young, L. H. [28] M. C. Cafeˆu, G. H. Silva, H. L. Teles, V. d. S. Bolzani, A Pfenning, Quim. Nova 2005, 28, 991. [29] V. Rukachaisirikul, N. Khamthong, Y. Sukpondma, C. Pakawatchai, S. Phongpaichit, J. Sakayaroj, K. Kirtikara, Chem. Pharm. Bull. 2009, 57, 1409. [30] X. N. Wang, R. X. Tan, J. K. Liu, J. Antibiot. 2005, 58, 268. [31] Y. Lin, X. Wu, S. Feng, G. Jiang, S. Zhou, L. L. P. Vrijmoed, E. B. G. Jones, Tetrahedron Lett. 2001, 42, 449. [32] G. Schneider, H. Anke, O. Sterner, Z. Naturforsch., C 1996, 51, 802. [33] R. A. Davis, J. Nat. Prod. 2005, 68, 769. [34] K. Liu, X. Ding, B. Deng, W. Chen, Biotechnol. Lett. 2010, 32, 689. [35] P. C. Healy, A. Hocking, N. Tran-Dinh, J. I. Pitt, R. G. Shivas, J. K. Mitchell, M. Kotiw, R. A. Davis, Phytochemistry 2004, 65, 2373. [36] R. A. Davis, G. K. Pierens, Magn. Reson. Chem. 2006, 44, 966. [37] F. Xu, Y. Zhang, J. Wang, J. Pang, C. Huang, X. Wu, Z. She, L. L. P. Vrijmoed, E. B. G. Jones, Y. Lin, J. Nat. Prod. 2008, 71, 1251. [38] S. Gunawan, B. Steffan, W. Steglich, Liebigs Ann. Chem. 1990, 825. [39] Y. Y. Li, Z. Y. Hu, Y. M. Shen, Nat. Prod. Commun. 2011, 6, 1843. [40] S. Tansuwan, S. Pornpakakul, S. Roengsumran, A. Petsom, N. Muangsin, P. Sihanonta, N. Chaichit, J. Nat. Prod. 2007, 70, 1620. [41] X. Liu, M. Dong, X. Chen, M. Jiang, X. Lv, J. Zhou, Appl. Microbiol. Biotechnol. 2008, 78, 241. [42] C. M. Oliveira, L. O. Regasini, G. H. Silva, L. H. Pfenning, M. C. M. Young, R. G. S. Berlinck, V. S. Bolzani, A. R. Araujo, Phytochemistry Lett. 2011, 4, 93. [43] Y. Lin, X. Wu, S. Feng, G. Jiang, J. Luo, S. Zhou, L. L. P. Vrijmoed, E. B. G. Jones, K. Krohn, K. Steingrover, F. Zsila, J. Org. Chem. 2001, 66, 6252. [44] X. Y. Wu, X. H. Liu, Y. C. Lin, J. H. Luo, Z. G. She, L. Houjin, W. L. Chan, S. Antus, T. Kurtan, B. Elssser, K. Krohn, Eur. J. Org. Chem. 2005, 4061. [45] X. Wu, X. Liu, G. Jiang, Y. Lin, W. Chan, L. L. P. Vrijmoed, Chem. Nat. Compd. 2005, 41, 27.

694

[46] [47] [48] [49] [50] [51] [52] [53] [54] [55] [56] [57] [58] [59] [60] [61] [62] [63] [64]


X. Liu, F. Xu., Y. Zhang, L. Liu, H. Huang, X. Cai, Y. Lin, W. Chan, Russ. Chem. Bull. 2006, 55, 1091. W. Gu, H. Ding, Chin. Chem. Lett. 2008, 19, 1323. X. N. Wang, R. X. Tan, F. Wang, W. Steglich, J. K. Liu, Z. Naturforsch., B 2005, 60, 333. D. N. Quang, D. D. Bach, T. Hashimoto, Y. Asakawa, Nat. Prod. Res. 2006, 20, 317. I. K. Lee, Y. W. Jang, Y. S. Kim, S. H. Yu, K. J. Lee, S. M. Park, B. T. OH, J. C. Chae, B. S. Yun, J. Antibiot. 2009, 62, 163. M. Adeboya, R. L. Edwards, T. Laessøe, D. J. Maitland, A. S. J. Whalley, J. Chem. Soc., Perkin Trans. 1 1995, 2067. M. O. Adeboya, R. L. Edwards, T. Lassøe, D. J. Maitland, L. Shields, A. S. J. Whalley, J. Chem. Soc., Perkin Trans. 1 1996, 1419. S. Y. Wang, Z. L. Xu, W. W. Mao, Z. G. She, N. Tan, C. R. Li, Y. C. Lin, Nat. Prod. Res. 2008, 22, 612. R. L. Edwards, D. J. Maitland, P. Pittayakhajonwut, A. J. S. Whalley, Chem. Forensic. Sci. 2001, 11, 1296. R. Siriwach, H. Kinoshita, S. Kitani, Y. Igarashi, K. Pansuksan, W. Panbangred, T. Nihira, J. Antibiot. 2011, 64, 217. C. Jime´nez-Romero, E. Ortega-Barra, A. E. Arnold, L. Cubilla-Rios, Pharm. Biol. 2008, 46, 700. Z. Y. Hu, Y. Y. Li, C. H. Lu, T. Lin, P. Hu, Y. M. Shen, Helv. Chim. Acta 2010, 93, 925. A. Schuffler, O. Sterner, H. Anke, Z. Naturforsch., C 2007, 62, 169. M. O. Adeboya, R. L. Edwards, T. Laessoee, D. J. Maitland, J. Chem. Res. 1995, 356. M. O. Adeboya, R. L. Edwards, T. Laessøe, D. J. Maitland, A. S. J. Whalley, Liebigs Ann. 1996, 1437. Y. W. Jang, I. K. Lee, Y. S. Kim, S. K. Lee, H. J. Lee, S. H. Yu, B. S. Yun, J. Antibiot. 2007, 60, 696. S. Boonphong, P. Kittakoop, M. Isaka, D. Pittayakhajonwut, M. Tanticharoen, Y. Thebtaranonth, J. Nat. Prod. 2001, 64, 965. A. Numata, C. Takahashi, Y. Ito, K. Minoura, T. Yamada, C. Matsuda, K. Nomoto, J. Chem. Soc., Perkin Trans. 1 1996, 239. J. S. Lee, K. S. Ko, H. S. Jung, FEMS Microbiology Lett. 2000, 187, 89. Received August 23, 2012

Quinone derivatives from the genus Rubia and their bioactivities.

Secondary Metabolites from the Marine Sponge Genus Phyllospongia.

Secondary metabolites of plants from the genus chloranthus: chemistry and biological activities.

Deep Sea Actinomycetes and Their Secondary Metabolites.

The genus Inula and their metabolites: from ethnopharmacological to medicinal uses.

Chemical Diversity and Biological Properties of Secondary Metabolites from Sea Hares of Aplysia Genus.

Secondary metabolites from the plants of the family saururaceae and their biological properties.

Recent advances regarding constituents and bioactivities of plants from the genus Hypericum.

Secondary Metabolites from Polar Organisms.

The Bioactive Secondary Metabolites from Talaromyces species.

Secondary metabolites from the fungus Emericella nidulans.

Natural dibenzo-α-pyrones and their bioactivities.

Antimutagenicity of secondary metabolites from higher plants.

The constituents of Michelia compressa var. formosana and their bioactivities.

Steroidal Saponins from the Genus Smilax and Their Biological Activities.

Cytochalasan and Tyrosine-Derived Alkaloids from the Marine Sediment-Derived Fungus Westerdykella dispersa and Their Bioactivities.

New triterpenoids from the fruiting bodies of Ganoderma lucidum and their bioactivities.

New alkenylated tetrahydropyran derivatives from the marine sediment-derived fungus Westerdykella dispersa and their bioactivities.

Secondary metabolites from the endophytic Botryosphaeria dothidea of Melia azedarach and their antifungal, antibacterial, antioxidant, and cytotoxic activities.

Secondary metabolites from the root of Lindera reflexa Hemsl.

Minor secondary metabolites from the bark of Entandrophragma congoënse (Meliaceae).

Secondary metabolites from Penicillium corylophilum isolated from damp buildings.

Essential oils: extraction, bioactivities, and their uses for food preservation.

Isolation and characterization of new secondary metabolites from Asphodelus microcarpus.