H. T. Li

Antioxidant and Anticancer Aporphine Alkaloids from the Leaves of Nelumbo nucifera Gaertn. cv. Rosa-plena

Fifteen compounds were extracted and purified from the leaves of Nelumbo nucifera Gaertn. cv. Rosa-plena. These compounds include liriodenine (1), lysicamine (2), (−)-anonaine (3), (−)-asimilobine (4), (−)-caaverine (5), (−)-N-methylasimilobine (6), (−)-nuciferine (7), (−)-nornuciferine (8), (−)-roemerine (9), 7-hydroxydehydronuciferine (10) cepharadione B (11), β-sitostenone (12), stigmasta-4,22-dien-3-one (13) and two chlorophylls: pheophytin-a (14) and aristophyll-C (15). The anti-oxidation activity of the compounds was examined by antiradical scavenging, metal chelating and ferric reducing power assays. The results have shown that these compounds have antioxidative activity. The study has also examined the antiproliferation activity of the isolated compounds against human melanoma, prostate and gastric cancer cells. The results shown that 7-hydroxydehydronuciferine (10) significantly inhibited the proliferation of melanoma, prostate and gastric cancer cells. Together, these findings suggest that leaves of Nelumbo nucifera Gaertn. cv. Rosa-plena are a good resource for obtaining the biologically active substances with antioxidant properties.

The Pharmacological Activities of (−)-Anonaine

Several species of Magnoliaceae and Annonaceae are used in Traditional Chinese Medicine. (−)-Anonaine, isolated from several species of Magnoliaceae and Annonaceae, presents antiplasmodial, antibacterial, antifungal, antioxidation, anticancer, antidepression, and vasorelaxant activity. This article provides an overview of the pharmacological functions of (−)-anonaine.

Secondary Metabolites from the Leaves of Ilex Cornuta

Ilex (Aquifoliaceae) species are found throughout China, and some are used extensively in traditional Chinese medicine. For example, I. rotunda is antipyretic and used for the treatment of the common cold, tonsillitis, and stomach and intestinal ulcers. I. pubescens is used for the treatment of coronary disease, myocardial infarction, dysentery, and erysipelas, and I. cornuta and I. latifolia are used for the treatment of headaches, toothaches, bloodshot eyes, and tinnitus [1]. Previous studies on the Ilex genus have resulted in the isolation of essential oils [2] triterpenes, triterpene glycosides [3–7], hemiterpene glycosides [8], and phenolic compounds [9, 10]. In the present study, 12 compounds were isolated from the leaves of I. cornuta. A MeOH extract of the I. cornuta leaves was concentrated to obtain a residue, which was partitioned between CH2Cl2 and H2O. The aqueous layer was extracted with n-BuOH, and then the n-BuOH layer was concentrated and analyzed by chromatography. As a result, 12 compounds, including eight flavonoids and four phenolic carboxylic acids, were isolated. The flavonoids were quercetin [11], quercetin 3-O-D-glucopyranoside [12], quercetin 3-O-D-galactopyranoside [13], quercetin 3-O-D-glucopyranosyl-(1 6)-D-glucopyranoside [14], isorhamnetin [15], isorhamnetin 3-O-Dglucopyranoside [15], isorhamnetin 3-O-D-galactopyranoside [15], and isorhamnetin 3-O-D-glucopyranosyl-(1 6)D-glucopyranoside [15]. The phenolic carboxylic acids were caffeic acid [16], p-hydroxybenzoic acid [17], protocatechuic acid [11], and vanillic acid [16]. This is the first report of the isolation of these compounds from this source. Leaves from I. cornuta Lindl. & Paxton were collected in Kaohsiung, Taiwan, in October 2006. Plant material was identified by Dr. Fu-Yuan Lu (Department of Forestry and Natural Resources, College of Agriculture, National Chiayi University, Chiayi City, Taiwan). A voucher specimen was deposited in the School of Medical and Health Sciences, Fooyin University, Kaohsiung, Taiwan. The air-dried leaves of I. cornuta (4.2 kg) were extracted with MeOH (5 10 L) at room temperature, and each MeOH fraction was concentrated under reduced pressure. The MeOH fractions were concentrated by evaporation and then partitioned to yield CH2Cl2 and aqueous extracts. The aqueous extracts were concentrated by evaporation and extracted with n-BuOH to give a n-BuOH layer and an aqueous layer. The n-BuOH layer (178.6 g) was subjected to silica gel chromatography (500 g, 70–230 mesh) with EtOAc–MeOH elution. Ten fractions were obtained. Part of fraction 2 (20.3 g) was subjected to silica gel chromatography with n-hexane–EtOAc (1:1, v/v). The volume fraction of EtOAc was gradually increased to yield five fractions (2-1–2-5). Fraction 2-2 (2.2 g) was further purified on a silica gel column using an n-hexane– CH2Cl2 mixture to obtain caffeic acid (7 mg), vanillic acid (3 mg), and p-hydroxybenzoic acid (5 mg). Fraction 2-4 (5.7 g) was further purified on a silica gel column with n-hexane–EtOAc elution to obtain isorhamnetin (12 mg). Part of fraction 3 (12.7 g) was subjected to silica gel chromatography with n-hexane–EtOAc (1:8, v/v). The volume fraction of EtOAc was gradually increased to yield quercetin (20 mg) and protocatechuic acid (34 mg). Part of fraction 4 (32.5 g) was subjected to silica gel chromatography with EtOAc–MeOH (20:1, v/v). The volume fraction of MeOH was gradually increased to yield isorhamnetin 3-O-D-glucopyranoside (67 mg) and isorhamnetin 3-O-D-galactopyranoside quercetin (42 mg). Part of fraction 5 (17.3 g) was subjected to silica gel chromatography with EtOAc–MeOH (20:1). The volume fraction of MeOH was gradually increased to obtain five further fractions (5-1–5-5). Fraction 5-3 (5.8 g) was further purified on a silica gel column with EtOAc–MeOH to obtain quercetin 3-O-D-glucopyranoside (78 mg) and quercetin 3-O-D-galactopyranoside (113 mg). Fraction 6-8 (22.7 g) was eluted with EtOAc–MeOH (8:1) and was repeatedly subjected to silica gel chromatography to give quercetin 3-O-D-glucopyranosyl-(1 6)-D-glucopyranoside (56 mg) and isorhamnetin 3-O-D-glucopyranosyl-(1 6)-D-glucopyranoside (24 mg).

Isoquinoline Alkaloids from Michelia fuscata

Two new isoquinoline alkaloids, fuscatine A (1) and fuscatine B (2), along with 21 compounds including eight isoquinoline alkaloids, northalifoline (3), thalifoline (4), corydaldine (5), N-methylcorydaldine (6), (6,7-dimethoxyisoquinolinyl)-(4′-methoxyphenyl)-methanone (7),(6,7-dimethoxyisoquinolinyl)-(4′-hydroxyphenyl)-methanone (8), liriodenine (9), and corydine (10); two steroids, β-sitosterone and stigmasterone; six benzenoids, p-hydroxybenzaldehyde, p-hydroxybenzoic acid, 3,4-dimethoxybenzoic acid, methylparaben, syringic acid, and coniferyl aldehyde; one quinone 2,6-dimethoxy-p-benzoquinone, and one sesquiterpene, caryophyllene oxide, are isolated from the stems of Michelia fuscata (Magnoliaceae). These compounds were characterized and identified by physical and spectral analysis.

Secondary Metabolites from the Unripe Fruits of Capsicum annuum var. conoides

Red pepper, Capsicum annuum (Solanaceae), is used as a spice all over the world. Red pepper is widely studied because its pungent principal component, capsaicin, has dietary, analgesic, and antioxidant activities [1]. The pungent principal component of red peppers is a group of acid amides of vanillylamine and C8 to C13 fatty acids, which are known generally as capsaicin [2]. More than 16 other capsaicinoids have been found as minor components [3]. Numerous studies have been done on the red pepper fruit, but there are few studies on stems [2–4]. Previously, we isolated 20 compounds, including ten amides, four steroids, and six benzenoids, from the stems of this plant [5]. The chemical constituents of unripe fruits of C. annuum L. var. conoides (Mill.) Irish have not yet been reported. This study has isolated secondary metabolites from the unripe fruits of C. annuum var. conoides. To further understand the chemotaxonomy and to continue searching for biologically and chemically novel agents from Solanaceous plants, the unripe fruits of C. annuum var. conoides were chosen for further phytochemical investigation. The MeOH extract of the unripe fruits of its plants were subjected to solvent partitioning and chromatographic separation to afford 17 pure substances. The chemical constituents in the plants of C. annuum var. conoides were separated by column chromatography. Investigation of the MeOH extract of the plants has led to the isolation of 17 compounds: three chlorophylls: pheophytin-a [6], 132-hydroxyl-(132-S)-pheophytin-a [7], and aristophyll-c [6]; six steroids: -sitosterol [8], stigmasterol [8], -sitostenone [8], stigmasta-4,22-dien-3-one [8], 6 -hydroxy-sitosterone [8], and 6 -hydroxystigmasterone [8]; seven benzenoids: p-hydroxybenzoic acid [9], p-hydroxybenzaldehyde [10], methylparaben [10], vanillin [10], isovanillin [10], ferulic acid [10], and syringic acid [10]; and one ionone: (+)-abscisic acid [11]. These compounds were obtained and characterized by comparison of their physical and spectral data (UV, IR, NMR, and MS) with values obtained in the literature. All of these compounds were found for the first time from this species. The specimen of C. annuum var. conoides was collected from Chiayi County, Taiwan in March, 2011. A voucher specimen was characterized by Dr. Jin-Cherng Huang of the Department of Forest Products Science and Furniture Engineering, National Chiayi University, Chiayi, Taiwan and deposited in the School of Medical and Health Sciences, Fooyin University, Kaohsiung, Taiwan. The air-dried unripe fruits of C. annuum var. conoides (5.7 kg) were extracted with MeOH (10 L 4) at room temperature, and the MeOH extract (56.2 g) was obtained upon concentration under reduced pressure. The MeOH extract was chromatographed over silica gel using CH2Cl2–MeOH as eluent to produce nine fractions. Part of fraction 1 (3.4 g) was subjected to silica gel column chromatography by eluting with n-hexane–acetone (60:1) to furnish 10 fractions (1-1–1-6). Fraction 1-2 (1.4 g) was further purified by another silica gel column using n-hexane–acetone (10:1) to obtain p-hydroxybenzoic acid (4 mg), p-hydroxybenzaldehyde (3 mg), and methylparaben (3 mg). Fraction 1-5 (0.2 g) was further purified by another silica gel column using n-hexane–acetone (15:1) to obtain vanillin (5 mg) and isovanillin (1 mg). Part of fraction 2 (8.6 g) was subjected to silica gel column chromatography by eluting with n-hexane–acetone (80:1) to furnish four fractions (2-1–2-4). Fraction 2-2 (2.7 g) was further purified by another silica gel column using n-hexane–acetone (70:1) to obtain pheophytin-a (14 mg), 132-hydroxyl-(132-S)-pheophytin-a (22 mg), and aristophyll-c (14 mg). Part of fraction 3 (5.6 g) was subjected to

Chemical constituents from the leaves of Cinnamomum burmannii

Cinnamomum burmannii Blume (Lauraceae) is a source of Indonesian cinnamon and is widely used as a spice in Indonesia [1]. The chemical constituents of the leaves of this plant have not yet been reported. Recently, we reported a new amide, cinnabutamine, along with five known amides from the stems of C. burmannii [2]. In the course of screening for biologically and chemically novel agents from Formosan plants in the family Lauraceae [3–12], C. burmannii was chosen for further phytochemical investigation. In this study, the MeOH extract of its leaves was subjected to solvent partitioning and chromatographic separation to afford 11 pure substances. The chemical constituents of the leaves of C. burmannii were separated by column chromatography. Eleven compounds, including squalene (1) [13], ficaprenol-10 (2) [14], methyl vanillate (3) [15], coumarin (4) [16], -sitostenone (5) [17], -sitosterol (6) [17], vanillic acid (7) [15], syringic acid (8) [15], (+)-abscisic acid (9) [18], p-hydroxybenzoic acid (10) [15], and kaempferol-3-O-rhamnoside (11) [19], were isolated from the leaves of C. burmannii. Compounds 1–3, 5–8, 10, and 11 were found for the first time from this plant. The specimen of C. burmannii was collected from Chiayi County, Taiwan in January 2009. A voucher specimen (Cinnamo. 10) was identified by Dr. Fu-Yuan Lu (Department of Forestry and Natural Resources College of Agriculture, National Chiayi University) and deposited in the Department of Medical Laboratory Sciences and Biotechnology, School of Medical and Heath Science, Fooyin University, Kaohsiung, Taiwan. The air-dried leaves of C. burmannii (4.7 kg) were extracted with MeOH (80 L 4) at room temperature, and a MeOH extract (186.4 g) was obtained upon concentration under reduced pressure. The MeOH extract was placed on a silica gel column and eluted with CH2Cl2 gradually enriched with MeOH to afford five fractions. Part of fraction 2 (9.52 g) was subjected to silica gel chromatography by eluting with n-hexane–EtOAc (100:1) and enriched with EtOAc to furnish four further fractions (2-1–2-4). Fractions 2-1 (3.05 g) eluted with n-hexane– EtOAc (60:1) was further purified by silica gel column chromatography using the same solvent system to give squalene (1) (12 mg) and ficaprenol-10 (2) (15 mg). Fractions 2-2 (2.57 g) and 2-3 (1.62 g) eluting with n-hexane–EtOAc (30:1) were further separated by silica gel chromatography to give methyl vanillate (3) (5 mg), and purified by preparative TLC (n-hexane– acetone, 20:1) to give coumarin (4) (19 mg) and -sitostenone (5) (12 mg), respectively. A part of fraction 3 (21.07 g) was subjected to silica gel chromatography by eluting with CH2Cl2–MeOH (100:1) and enriched with MeOH to furnish four further fractions (3-1–3-4). Fraction 3-1 (6.52 g) eluted with CH2Cl2–MeOH (80:1) was further purified by silica gel column chromatography using n-hexane–acetone (10:1) to give -sitosterol (6) (10 mg). Fraction 3-2 (8.73 g) eluting with CH2Cl2– MeOH (60:1) was further purified by silica gel column chromatography using the same solvent system and preparative TLC (n-hexane–acetone, 4:1) to give vanillic acid (7) (6 mg) and syringic acid (8) (5 mg). Fraction 3-3 (0.43 g) was further purified by another silica gel column using n-hexane–acetone (3:1) to obtain (+)-abscisic acid (9) (9 mg). A part of fraction 4 (15.33 g) was subjected to silica gel chromatography eluting with CH2Cl2–MeOH (40:1) and enriched gradually with MeOH to give three fractions (4-1–4-3). Fraction 4-2 (8.21 g) was further separated by silica gel column chromatography using the same solvent system and purified by preparative TLC (CH2Cl2–MeOH, 20:1) to yield p-hydroxybenzoic acid (10) (6 mg). Kaempferol3-O-rhamnoside (11) (8 mg) was further purified on a silica gel column using CH2Cl2–MeOH (10:1) from fraction 4-3.

Secondary Metabolites from the Stems of Capsicum annuum var. conoides

Red pepper, Capsicum annuum (Solanaceae), is used as a spice all over the world. Red pepper is studied actively because its pungent principal component, capsaicin, has a dietary effect, analgesic activity, and antioxidant activity [1]. The pungent principal component of red peppers is a group of acid amides of vanillylamine and C8 to C13 fatty acids, which are known generally as capsaicin [2]. More than 16 other capsaicinoids have been found as minor components [3]. Numerous studies have been done on the red pepper fruit, but there are few studies on stems [2–4]. The chemical constituents of stems of C. annuum L. var. conoides Irish have not yet been reported. This study has shown the isolation of secondary metabolites from the stems of C. annuum var. conoides. To further understand the chemotaxonomy and to continue our search for biologically and chemically novel agents from Solanaceous plants, the stems of C. annuum collected from Chiayi County, Taiwan in March, 2011 were chosen for further phytochemical investigation. The MeOH extract of its plants were subjected to solvent partitioning and chromatographic separation to afford 19 pure substances. The chemical constituents in the plant of C. annuum var. conoides were separated by column chromatography. Investigation of the MeOH extract of the plants has led to the isolation of 21 compounds, 10 amides 1–10, four steroids 11–14, one lignan 15, and six benzenoids 16–21. These compounds were obtained and characterized by comparison of their physical and spectral data (UV, IR, NMR, and MS) with values in the literature. All of these compounds were found for the first time from this species. The specimen of C. annuum var. conoides Irish was collected from Chiayi County, Taiwan in March, 2011. A voucher specimen was characterized by Dr. Jin-Cherng Huang of the Department of Forest Products Science and Furniture Engineering, National Chiayi University, Chiayi, Taiwan and deposited in the School of Medical and Health Sciences, Fooyin University, Kaohsiung, Taiwan. The air-dried stems of C. annuum var. conoides (6.2 kg) were extracted with MeOH (10 L 4) at room temperature, and an MeOH extract (64.3 g) was obtained upon concentration under reduced pressure. The MeOH extract was chromatographed over silica gel using CH2Cl2–MeOH as eluent to produce 10 fractions. Part of fraction 2 (6.52 g) was subjected to silica gel column chromatography by eluting with n-hexane–acetone (50:1) to furnish seven fractions (2-1–2-7). Fraction 2-2 (2.52 g) was further purified by another silica gel column using n-hexane–acetone (10:1) to obtain p-hydroxybenzoic acid (16) (2 mg) and p-hydroxybenzaldehyde (17) [5] (5 mg). Fraction 2-3 (1.86 g) was further purified by another silica gel column using n-hexane–acetone (9:1) to obtain vanillic acid (18) [5] (2 mg) and isovanillic acid (19) [5] (3 mg). Part of fraction 3 (5.12 g) was subjected to silica gel column chromatography by eluting with n-hexane–acetone (40:1), then enriched with acetone to furnish eight fractions (3-1–3-8). Fraction 3-1 (1.24 g) eluted with n-hexane–EtOAc (30:1) was further separated using silica gel column chromatography and preparative TLC (n-hexane–EtOAc, 10:1) to give a mixture of -sitosterol (11) [6] and stigmasterol (12) [6] (37 mg). Fraction 3-2 (1.41 g) was further purified on a silica gel column using the CH2Cl2–MeOH system to obtain (+)-syringaresinol (15) [7] (5 mg), ferulic acid (20) [8] (3 mg), and hydroferulic acid (21) [9] (2 mg).

Cinnapine, a New Pyridine Alkaloid from Cinnamomum Philippinense

Cinnapine (1), a new pyridine alkaloid, has been isolated from the roots of Cinnamomum philippinense (Lauraceae). The structure was characterized and identified by spectral analysis.

Secondary Metabolites from the Leaves of Aquilaria sinensis

Lignum Aquilariae Resinatum has been widely used in the treatment of various kinds of pain, cough, and anaphylaxis for hundreds of years in Asia, especially in China, Vietnam, and Indonesia. The genus Aquilaria (Thymelaeaceae) is widely distributed in Asia. Aquilaria sinensis Gilg is of particular interest economically because it is the principal source of agarwood, one of the most highly valued forest products currently traded internationally. The leaves of A. sinensis Gilg, which is widely cultivated in Guangdong, Hainan, and Taiwan Provinces in China, are reported to be used locally in trauma-related diseases such as fracture, bruise, etc. [1]. Previous phytochemical investigations on Chinese eaglewood have revealed characteristic sesquiterpenes and chromone derivatives [2–15] but few on the chemical constituents of the leaves [16, 17]. The analgesic and anti-inflammatory activities of the ethanol extract of A. sinensis leaves were observed in various experimental models related to nociception and inflammation, thus providing some evidence for its traditional use. In the investigations of interrelated studies, it was found that agarwood has significant anticancer activities [18], analgesic and anti-inflammatory activities [19], and anti-depressant activities [20, 21]. These observations provide useful information for potential chemopreventive drug design. The MeOH extract of its leaves were subjected to solvent partitioning and chromatographic separation to afford 12 pure substances. Twelve compounds, including three flavonoids, 5-hydroxy-4 ,7-dimethoxyflavonoid (1) [22], luteolin-7,3 ,4 -trimethyl ether (2) [23], and 5,3 -dihydroxy-7,4 -dimethoxyflavone (3) [24], five benzenoids, methylparaben (4) [25], vanillic acid (5) [26], p-hydroxybenzoic acid (6) [27], syringic acid (7) [28], and isovanillic acid (8) [28], and four steroids, -sitosterol (9) [29], stigmasterol (10) [29], -sitostenone (11) [29], and stigmasta-4,22-dien-3-one (12) [29], were isolated from the leaves of A. sinensis. All of these compounds (1–12) were obtained for the first time from the leaves of this plant. The specimen of A. sinensis was collected from Guansi Township, Hsinchu County, Taiwan in May, 2007. A voucher specimen was identified by Prof. Fu-Yuan Lu (Department of Forestry and Natural Resources, College of Agriculture, National Chiayi University) and was deposited in the School of Medical and Health Sciences, Fooyin University, Kaohsiung, Taiwan. The leaves (1.2 kg) of A. sinensis were air dried and extracted repeatedly with MeOH (6 L 8) at room temperature. The combined MeOH extracts (31.3 g) were then evaporated and further separated into four fractions by column chromatography on silica gel (4.3 kg, 70–230 mesh) with gradients of n-hexane–CH2Cl2–acetone–MeOH. Part of fraction 1 (11.6 g) was subjected to silica gel chromatography by eluting with n-hexane–acetone (50:1), enriched with acetone, to furnish three further fractions (1-1–1-3). Fraction 1-1 (2.8 g) was further purified on a silica gel column using n-hexane–acetone mixtures to obtain 5-hydroxy-4 ,7-dimethoxyflavonoid (1) (4.8 mg). Part of fraction 1-2 (2.5 g) was subjected to silica gel chromatography by eluting with n-hexane–acetone (50:1), enriched gradually with acetone, to furnish two fractions (1-2-1–1-2-2). Fraction 1-2-1 (0.5 g) was further purified on a silica gel column using n-hexane–acetone mixtures to yield luteolin-7, 3 ,4 -trimethyl ether (2) (3.4 mg) and 5,3 -dihydroxy-7,4 -dimethoxyflavone (3) (3.2 mg). Fraction 1-2-2 (0.5 g) was further purified on a

Chemical Constituents of Cultured Soft Coral Sinularia flexibilis

Diterpenes of the cembrane type are some of the most frequently encountered metabolites in soft corals of the order Alcyonacean [1]. Of particular interest, cembrane-type diterpenoids have been reported to display a variety of biological activities, including antitumor and antifouling activities [2]. Marine-derived compounds obtained from soft corals are believed to yield many potential candidate compounds for treating inflammatory disease, particularly for treating pain [3–6]. The natural marine compound sinularin has been well studied and was shown by Weinheimer et al. in 1977 to have anticancer activity against the human epidermoid carcinoma cell line and the murine P388 lymphocytic leukemia cell line from the soft coral Sinularia flexibilis [7]. As part of our continuing investigation of the phytochemical and bioactive compounds of S. flexibilis, five cembranoids, isosinulaflexiolide K (1) [8], sinulaflexiolide K (2) [9], sandensolide (3) [10], sinularin (4) [7] and dendronpholide F (5) [11] were obtained by systematic extraction and isolation from this soft coral. All of these known compounds were identified by direct comparison with authentic sample (TLC, UV, IR, ESI-MS and NMR) and the literature [8–11]. Compounds 1–3, 5 were found for the first time from this cultured soft coral. The one light yellow cultured soft corals S. flexibilis was initially collected from the wild and subsequently grown for 8 years in an 80 ton cultivation tank located in the National Museum of Marine Biology & Aquarium. The tank was a flowthrough seawater system, and deliberate feeding was not required. The specimen was collected by hand in January 2013, frozen immediately, and kept frozen until extraction. This soft coral was identified by Chang-Feng Dai (Institute of Oceanography, National Taiwan University). A voucher specimen was deposited in the National Museum of Marine Biology & Aquarium (2013CSC-2). The frozen S. flexibilis (4.2 kg, wet weight) was freeze-dried, and the resulting material (450 g) was minced and extracted exhaustively with EtOAc (6 2 L). The EtOAc extract was evaporated under reduced pressure to afford a residue (30.5 g), and the residue was subjected to column chromatography on silica gel using n-hexane, an n-hexane–EtOAc mixture of increasing polarity, and finally pure acetone to yield 13 fractions. Part of fraction 11 was subjected to silica gel chromatography by eluting with n-hexane–EtOAc (1:2 to 1:3) enriched with EtOAc to furnish four further fractions (11-1–11-4). Part of fraction 11-2 (3.2 g) was subjected to silica gel chromatography by eluting with CH2Cl2–MeOH (100:1) enriched gradually with acetone to furnish four fractions (11-2-1–11-2-4). Fractions 11-2-1 (0.4 g) were subjected to further silica gel column chromatography and purified by preparative TLC (CH2Cl2–MeOH, 200:1) to yield isosinulaflexiolide K (1, 5 mg) and sinulaflexiolide K (2, 2mg). Fractions 11-2-2 (1.2 g) were subjected to further silica gel column chromatography and purified by preparative TLC (CH2Cl2–MeOH, 100:1) to yield sinularin (4, 203 mg) and sandensolide (3, 127 mg). Fractions 11-2-3 (0.2 g) were subjected to further silica gel column chromatography and purified by preparative TLC (CH2Cl2–MeOH, 100:1) to yield sandensolide (3, 25 mg). Fractions 11-2-4 (0.3 g) were subjected to further silica gel column chromatography and purified by preparative TLC (CH2Cl2–MeOH, 200:1) to yield dendronpholide F (5, 7 mg).