Terpenes and polybromoindoles from the marine red alga Laurencia decumbens (Rhodomelaceae)

Two new brominated diterpenes, namely, laurendecumtriol (1) and 11-O-deacetylpinnaterpene C (2), one new polybromoindole, 2,3,4,6-tetrabromo-1-methyl-1H-indole (7), and six known natural products were isolated and identified from the marine red alga Laurencia decumbens. Their structures were elucidated on the basis of detailed spectroscopic and mass-spectrometric analysis as well as by comparison with literature data. Based on 2D-NMR experiments, the previously reported NMR data for pinnaterpene C (3) were reassigned.

羟基自由基降解琼胶及其产物的活性研究

琼胶是一种从石花菜等红藻中提取的，目前生产工艺和结构等方面研究比较成熟的海藻多糖，广泛应用于医药、仪器等行业。但是，海藻多糖因为具有分子量大，粘度大，溶解度较小的等特点，而使其应用范围受到限制。利用降解的手段对其进行修饰，降低分子量和粘度，改善溶解性，可以拓展其应用范围。并且根据文献报道，琼 胶寡糖具有一些特殊的生物活性，如抗氧化性，抗炎症等。因此，对琼胶降解的研究具有生要意义。本研究中，为了选择一种合适的降解方法，进行了几种水解方法的尝试，其中包括在不同湿度和酸度下盐酸水解，过氧化氢和醋酸催化水解，Fenton体系羟基自由基降解。对于酸水解和Fenton体系氧化还原降解方法，通过粘度法对反应的速度进行了比较，表明氧化还原降解反应中琼胶的粘度降低比较快，并且具有代表性和新意，确定为本实验的降解琼胶的方法并对氧化还原降解所得的产物进行了活性实验。通过模仿自然界普遍存在的氧化还原降解反应，利用Vc诱导的Fenton体系产生的羟基自由基氧化还原降解琼胶得到低分子量的琼胶。降解产物经过高速离心、60％乙醇沉淀，除去分子量比较大的降解产物和磷酸盐，得到可溶于60％乙醇的分子量估计小于3000的降争产物，其产率为85％。利用经Sephadex-G25凝胶色谱分离所香的不同分子量的级分进行分子量和α－葡萄糖苷酶抑制活性关系的实验。降解产物对α－葡萄糖苷酶的抑制率和各级分的浓度呈线性正相关，并且各级分的IC_(50)则随着分子量的降低而降低。另外，对所得的降解产物混合物进行了红外吸收光谱、质子去偶核磁共震碳谱和负离子基质辅助激光诱导－飞行时间质谱结构分析。结果表明，氧化还原降解反应的专一性差，在得到寡糖的同时，在光谱图中出现一些比较复杂的副产物的结构信息。最后，根据MTT法的原理，以有体皮肤成纤维细胞为材料，通过紫外线辐射产生自由基造成氧化损伤，研究降解产物对成纤维细胞的保护作用。当无紫外线辐射时，降解产物对成纤维细胞具有显著的促进生长增殖作用：当经UVa、UBb辐射时则可以显著地表现出对损伤的保护作用，并且这种促进生长和保护作用呈显著的量效关系，表明降解产物具有清除基自由基的作用。但是，因为氧化还原降解以应的机理尚不十分明的以及琼羟胶的特殊结构，使得反应的副产物很难预测，也就使得分离工作难以进行，所以，根据目前所得的信息，尚不能确定是降解产物的什么级分产生的以上两种生物活性。

海洋红藻多管藻和松节藻的化学成分及抗氧化活性研究

海洋生物具有产生丰富多样的次生代谢产物的能力，其中红藻门松节藻科海藻卤代次生代谢产物以其结构新颖、生物活性独特引起了天然产物化学家的重视。 本论文对海洋红藻多管藻和松节藻进行了化学成分研究，综合利用各种色谱学方法 (硅胶柱层析、反相硅胶柱层析、凝胶Sephadex LH-20柱层析、半制备高效液相色谱以及重结晶等) 和现代波谱学技术 (IR、UV、EI-MS、FAB-MS、HR-ESI-MS、CD、1H-NMR、13C-NMR、DEPT、1H-1H COSY、HSQC、HMBC等)，共分离鉴定了100个化合物，发现25个新化合物。 从多管藻中分离鉴定38个化合物 (24个溴酚化合物)，其中7个新化合物 (均为溴酚化合物)，包括1个菲并呋喃结构溴酚 (P1), 2个二氢菲结构溴酚 (P2, P3)，1个含 5,7-dihydrodibenzo[c,e]oxepine 结构溴酚 (P4)和3个简单溴酚 (P5, P6, P7)。P1 (urceolatin) 属首例报道的具有菲并呋喃结构的天然产物，从该种中分离的化合物P12 和 P13 可能是其生源合成的前体。P2和P3为第二例报道的具有二氢菲结构的溴酚化合物。 从松节藻中分离并鉴定了62 个化合物，其中18 个为溴酚类新化合物，44 个为已知化合物。化合物具有多变的取代基团，包括2 个脲基吡咯烷酮溴酚化合物 (R1, R2), 4 个γ-脲基丁酸溴酚化合物 (R3-R6)，5 个酰胺溴酚化合物 (R7, R8, R9, R13, R14)，1 个溴酚砜化合物 (R12), 1 个Xanthene 溴酚化合物 (R10)和5 个简单溴酚化合物 (R11, R15, R16, R17, R18)。R1、R2 是首例报道的含有脲基吡咯烷酮片段的天然产物，R10 为首次报道的溴代Xanthene 类天然产物。 对分离到的化合物进行了清除DPPH 和ABTS两种自由基活性的筛选。结果发现溴酚类天然产物具有显著的DPPH自由基清除活性，其中R3 的IC50 仅为3.3 μM, 其活性强度约为阳性对照BHT (IC50 为82.1 μM) 的24倍。另外，溴酚类天然产物对ABTS自由基有较强的清除活性，R2 的TEAC（Trolox efficency activity capacity）值为5.2 mM，约为阳性对照 (ascorbic acid, 1.02 mM) 的 5 倍。初步的构效关系研究发现，稠环分子、多羟基和邻位甲氧基等结构特点能有效增强DPPH 自由基清除活性；特殊取代基如脲基、吡咯烷酮等含有氮原子的基团，能有效增强ABTS 自由基清除活性，多羟基、溴代等结构特点也使其活性有所增强。 本研究结果丰富了海藻卤代化合物的结构类型，为多管藻和松节藻的合理利用提供了一定的科学依据。

Dibenzyl bromophenols with diverse dimerization patterns from the brown alga Leathesia nana

Six novel dibenzyl bromophenols (1-6) with different dimerization patterns and two propyl bromophenol derivatives (7 and 8), together with 11 known bromophenol derivatives, were isolated from the ethanolic extract of the brown alga Leathesia nana. On the basis of spectroscopic methods the structures of the new compounds were determined as 5,6'-diethyloxymethyl-3,4,2'-tribromo-2,3',4'-trihydroxydiphenyl ether (1), 2-(2,3-dibromo-4,5-dihydroxybenzyl)-3,5-dihydroxy-4-methoxybenzyl alcohol (2), 6-(2,3-dibromo-4,5dihydroxybenzyl)-2,3-dibromo-4,5-dihydroxy benzyl methyl ether (3), 9,10-dihydro-9,10-dimethoxy-3,4,7,8-tetrabromo-1,2,5,6-tetrahydroxyanthracene (4), (+)-3-(2,3-dibromo-4,5-dihydroxyphenyl)-4-bromo-5,6-dihydroxy-1,3-dihydroisobenzofuran (5), rel-(4aS*,10aR*)-(+/-)-6,7-dibromo-4a-hydroxy-3,8-dihydroxymethyl-10a-methoxy- 1,4,4a, 10a-tetrahydrodibenzo[b,e][1,4]dioxin-1-one (6), (E)-2-methyl-3-(2,3-dibromo-4,5-dihydroxyphenyl)propenal (7), and 2-methyl-3-(2,3-dibromo-4,5-dihydroxyphenyl)-1-propanol (8). Some compounds including 3 showed in vitro selective cytotoxicity against several human cancer cell lines. This is the first brown alga to be reported containing bromophenols.

Bromophenols from the red alga Rhodomela confervoides

Six new bromophenols, 3-bromo-4,5-bis(2,3-dibromo-4,5-dihydroxybenzyl)pyrocatechol (1), 2,2',3-tribromo-3',4,4',5-tetrahydroxy-6'-hydroxymethyldiphenylmethane (2), 2,2',3-tribromo-3',4,4',5-tetrahydroxy-6'-ethyloxymethyldiphenylmethane (3),(+/-)-2-methyl-3-(2,3-dibromo-4,5-dihydroxyphenyl)propylaldehyde (4), (+/-)-2-methyl-3-(2,3-dibromo-4,5-dihydroxyphenyl)propylaldehyde dimethyl acetal (5), and 3-bromo-4,5-dihydroxybenzoic acid methyl ester (6), together with eight known bromophenols, 3-bromo-4,5-dihydroxybenzaldehyde (7), 2,3-dibromo-4,5-dihydroxybenzyl alcohol (lanosol, 8), 2,3-dibromo-4,5-dihydroxybenzyl methyl ether (9), 2,3-dibromo-4,5-dihydroxybenzyl ethyl ether (10), 2,3-dibromo-4,5-dihydroxybenzylaldehyde (11), bis(2,3-dibromo-4,5-dihydroxybenzyl) ether (12), 3-bromo-4-(2,3-dibromo-4,5-dihydroxybenzyl)-5-methoxymethylpyrocatechol (13), and 2,2',3,3'-tetrabromo-4,4',5,5'-tetrahydroxydiphenyl methane (14), were isolated from the red alga Rhodomela confervoides. Their structures were elucidated by chemical and spectroscopic methods including IR, HRFABMS, and 1D and 2D NMR techniques.

Bromophenols coupled with methyl gamma-ureidobutyrate and bromophenol sulfates from the red alga Rhodomela confervoides

Four new bromophenols C-N coupled with methyl gamma-ureidobutyrate (1-4), a phenylethanol bromophenol (5), and three phenylethanol sulfate bromophenols (6-8) have been isolated from polar fractions of an ethanolic extract of the red alga Rhodomela confervoides. On the basis of spectroscopic evidence including HRMS and 2D NMR data, the structures of the new compounds were determined as methyl N'-(2,3-dibromo-4,5-dihydroxybenzyl)-gamma-ureidobutyrate (1), methyl N,N'-bis(2,3-dibromo-4,5-dihydroxybenzyl)-gamma-ureidobutyrate (2), methyl N'-[3-bromo-2-(2,3-dibromo-4,5-dihydroxybenzyl)-4,5-dihydroxybenzyl]-gamma-ureidobutyrate (3), methyl N'-(2,3-dibromo-4,5-dihydroxybenzyl)-A7-[3-bromo2-(2,3-dibromo-4,5-dihydroxybenzyl)-4,5-dihydroxybenzyl]-gamma-ureidobutyrate (4), 2,3-dibromo-4,5-dihydroxyphenylethanol (5), 2,3-dibromo-4,5-dihydroxyphenylethanol Sulfate (6), 3-bromo-4,5-dihydroxyphenylethanol sulfate (7), and 3-bromo2-(2,3-dibromo-4,5-dihydroxybenzyl)-4,5-dihydroxyphenylethanol sulfate (8). The cytotoxicity of all compounds was evaluated against several human cancer cell lines including human colon cancer (HCT-8), hepatoma (Bel7402), stomach cancer (BGC-823), lung adenocarcinoma (A549), and human ovarian cancer (A2780). Among them, the phenylethanol and the phenylethanol sulfate bromophenols (5-8) showed moderate cytotoxicity against all tested cell lines.

Bromophenols coupled with nucleoside bases and brominated tetrahydroisoquinolines from the red alga Rhodomela confervoides

Three new bromophenols C-N coupled with nucleoside base derivatives (1-3) and three new brominated 1,2,3,4-tetrahydroisoquinolines (5-7, together with a new brominated tyrosine derivative (4, have been isolated from polar fractions of an ethanolic extract of the red alga Rhodomela confervoides. By spectroscopic and chemical methods including HRMS and 2D NMR data, their structures were determined as 7-[3-bromo-2-(2,3-dibromo-4,5-dihydroxybenzyl)-4,5-dihydroxybenzyl]-3,7-dihydro-1H-purine-2,6-dione (1), 7-(2,3-dibromo-4,5-dihydroxybenzyl)-3,7-dihydro-1H-purine-2,6-dione (2, 9-[3-bromo-2-(2,3-dibromo-4,5-dihydroxybenzyl)-4,5-dihydroxybenzyl]adenine (3), (-)-8S-(3-bromo-5-hydroxy-4-methoxy)phenylalanine (4), (-)-3S-8-bromo-6-hydroxy-7-methoxy-1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid (5), methyl (-)-3S-8-bromo-6-hydroxy-7-methoxy-1,2,3,4-tetrahydroisoquinoline-3-carboxylate (6), and methyl (-)-3S-6-bromo-8-hydroxy-7-methoxy-1,2,3,4-tetrahydroisoquinoline-3-carboxylate (7). Compounds 5-7 were semisynthesized by using 4 as the starting material.

Cadinane Sesquiterpenes from the brown alga Dictyopteris divaricata

Seven new cadinane sesquiterpenes, (-)-(1R,6S,7S,10R)-1-hydroxycadinan-3-en-5-one (1), (+)-(1R,5S,6R,7S, 10R)-cadinan-3-ene-1,5-diol (2), (+)-(1R,5R,6R,7S,10R)-cadinan-3-ene-1,5-diol (3), (+)-(1R,5S,6R,7S,10R)-cadinan-4(11)-ene-1,5-diol (4), (+)-(1R,5R,6R,7R,10R)-cadinan-4(11)-ene-1,5,12-triol (5), (-)-(1R,4R,5S,6R,7S, 10R)-cadinan-1,4,5-triol (6), and (-)-(1R,6R,7S,10R)-11-oxocadinan-4-en-1-ol (7), together with nine known compounds were isolated from the brown alga Dictyopteris divaricata. The structures of the new natural products, as well as their absolute configuration, were established by means of spectroscopic data including IR, HRMS, 1D and 2D NMR, single-crystal X-ray diffraction, and CD. All compounds were inactive against several human cancer cell lines including lung adenocarcinoma (A549), stomach cancer (BGC-823), breast cancer (MCF-7), hepatoma (Bel7402), and colon cancer (HCT-8) cell lines.

Minor sesquiterpenes with new carbon skeletons from the brown alga Dictyopteris divaricata

Five minor sesquiterpenes (1-5) with two novel carbon skeletons, together with a minor new oplopane sesquiterpene ( 6), have been isolated from the brown alga Dictyopteris divaricata. By means of spectroscopic data including IR, HRMS, 1D and 2D NMR, and CD, their structures including absolute configurations were assigned as (+)-(1R, 5S, 6S, 9R)3- acetyl-1-hydroxy-6-isopropyl-9-methylbicyclo[4.3.0] non-3-ene ( 1), (+)-(1R, 3S, 4S, 5R, 6S, 9R)-3-acetyl-1,4-dihydroxy-6- isopropyl-9-methylbicyclo[4.3.0] nonane (2), (+)-(1R, 3R, 4R, 5R, 6S, 9R)-3-acetyl-1,4-dihydroxy-6-isopropyl-9-methylbicyclo[ ;4.3.0] nonane ( 3), (+)-(1S, 2R, 6S, 9R)-1-hydroxy-2-(1-hydroxyethyl)-6-isopropyl-9-methylbicyclo[4.3.0] non-4-en-3-one (4), (-)-( 5S, 6R, 9S)-2-acetyl-5-hydroxy-6-isopropyl-9-methylbicyclo[4.3.0] non-1-en-3-one ( 5), and (-)-( 1S, 6S, 9R)- 4-acetyl- 1-hydroxy-6-isopropyl-9-methylbicyclo[ 4.3.0] non-4-en-3-one ( 6). Biogenetically, the carbon skeletons of 1-6 may be derived from the co-occurring cadinane skeleton by different ring contraction rearrangements. Compounds 1-6 were inactive (IC50 > 10 mu g/mL) against several human cancer cell lines.

Norsesquiterpenes from the brown alga Dictyopteris divaricata

Three bisnorsesquiterpenes (1-3) with novel carbon skeletons and a norsesquiterpene (4) have been isolated from the brown alga Dictyopteris divaricata. By means of spectroscopic data including IR, HRMS, 1D and 2D NMR techniques, single-crystal X-ray diffraction, and CD, their structures including absolute configurations were proposed as (+)-1R,6S,9R)-1-hydroxyl-6-isopropyl-9-methylbicyclo[4.3.0]non-4-en3-one (1), (-)-(1S,6S,9R)-1-hydroxyl-6-isopropyl-9-methylbicyclo[4.3.0] non-4-en-3-one (2), (+)-(5S,6R,9S)5-hydroxyl-6-isopropyl-9-methylbicyclo [4.3.01 non-1-en-3-one (3), and (-)-(1R,7S,10R)-1-hydroxy-1lnorcadinan-5-en-4-one (4). Biogenetically, the carbon skeleton of 1-3 may be derived from the co-occurring cadinane skeleton by ring contraction and loss of two carbon units, and compound 4 from the oxidation of cadinane derivatives. Compounds 1-4 were inactive (IC50 > 10 mu g/mL) against several human cancer cell lines including lung adenocarcinoma (A549), stomach cancer (BGC-823), breast cancer (MCF-7), hepatoma (Bel7402), and colon cancer (HCT-8) cell lines.

Sesquiterpenes from the red alga Laurencia tristicha

Seven new sesquiterpenes (1-7), together with seven known sesquiterpenes, aplysin (8), aplysinol (9), gossonorol (10), 7,10-epoxy-ar-bisabol-11-ol (11), 10-epi-7,10-epoxy-ar-bisabol-11-ol (12), johnstonol (13), and laurebiphenyl (14), have been isolated from the red alga Laurencia tristicha. The structures of new compounds were established as laur-11-en-2,10-diol (1), laur-11-en-10-ol (2), laur-11-en-1,10-diol (3), 4-bromo-1,10-epoxylaur-11-ene (4), cyclolauren-2-ol (5), laurentristich-4-ol (6), and ar-bisabol-9-en-7,11-diol (7) by means of spectroscopic methods including IR, HRMS, and ID and 21) NMR techniques. Compound 6 possessed a novel rearranged skeleton. All compounds were tested against several human cancer cell lines including lung adenocarcinoma (A549), stomach cancer (BGC-823), hepatoma (Bel 7402), colon cancer (HCT-8), and HELA cell lines. Laurebiphenyl (14) showed moderate cytotoxicity against all tested cell lines, with IC50 values of 1.68, 1.22, 1.91, 1.77, and 1.61 mu g/mL, respectively. Other compounds were inactive (IC50 > 10 mu g/mL).

Bromophenol derivatives from the red alga Rhodomela confervoides

Eight new bromophenol derivatives, 2,3-dibromo-4,5-dihydroxybenzyl methyl sulfoxide (1), 4-(2,3-dibromo-4,5-dihydroxyphenyl)-3-butene-2-one (2), 2-(3-bromo-5-hydroxy-4-methoxyphenyl)-3-(2,3-dibromo-4,5-dihydroxyphenyl)propionic acid (3), 2-(3-bromo-5-hydroxy-4-methoxyphenyl)-3-(2,3-dibromo-4,5-dihydroxyphenyl)propionic acid methyl ester (4), 2-phenyl-3-(2,3-dibromo-4,5-dihydroxyphenyl)propionic acid (5), 4'-methoxy-2",3',3"-tribromo-4",5',5"-trihydroxydiphenylacetic acid (6), and 3-bromo-5-hydroxy-4-methoxyphenylacetic acid (7) and its methyl ester (8), together with a known bromophenol, 3-bromo-5-hydroxy4-methoxybenzoic acid (9), were isolated from the red alga Rhodomela confervoides. Their structures were elucidated by spectroscopic methods including IR, EIMS, FABMS, ESIMS, HRFABMS, HRESIMS, 1D and 2D NMR, and single-crystal X-ray structure analysis. Compounds 1-4, 8, and 9 were found inactive against several human cancer cell lines and microorganisms.

Bromophenols coupled with derivatives of amino acids and nucleosides from the red alga Rhodomela confervoides

Three new bromophenols coupled with pyroglutamic acid derivatives and one bromophenol coupled with deoxyguanosine were obtained from the red alga Rhodomela confervoides. By spectroscopic methods including 2D NMR and single-crystal X-ray structure analysis their structures were elucidated as N-(2,3-dibromo-4,5-dihydroxybenzyl)methyl pyroglutamate (1), N-(2,3-dibromo-4,5-dihydroxybenzyl)pyroglutamic acid (2), N-[3-bromo-2-(2,3-dibromo-4,5-dihydroxybenzyl)-4,5-dihydroxybenzyllmethyl pyroglutamate (3), and 2-N-(2,3-dibromo-4,5-dihydroxybenzylamino)deoxyguanosine (4), respectively. Compounds 1-4 were evaluated against several microorganisms and human cancer cell lines, but found inactive. To our knowledge this is the first report of bromophenols coupled with amino acid or nucleoside derivatives through the C-N bond.

A novel polyhydroxyl sterol from Asterina pectinifera

A novel polyhydroxyl sterol ( 1) along with one known polyhydroxyl sterol (2), and two known monoglycosides, asterosaponin P-1 (3) and its desulfated monoglycoside (4), have been isolated from the whole bodies of a common Pacific starfish Asterina pectinifera. The structure of the new polyhydroxyl sterol was determined as 15beta, 16beta-isopropylidenedioxy-5alpha-cholestane-3beta, 4beta, 6alpha, 7alpha, 8,26-hexaol by spectroscopic methods, including FABMS, HR-FABMS, 1D and 2D NMR techniques.

Prevention of fish oil rancidity by phlorotannins from Sargassum kjellmanianum

Known only in the Phaeophyceae, phlorotannins (brown algal polyphenols) are a class of natural products with potential uses in pharmacology. This study reports that phlorotannins from Sargassum kjellmanianum can prevent fish oil from rancidification; the antioxidation activity was about 2.6 times higher than that of 0.02% BHT (tertbutyl-4-hydroxytoluene).