Efficient synthesis of octandrenolone and related dipyranoacetophenones

Octandrenolone (1) was prepared in high yield by condensation of 2', 4',6'-trihydroxyacetophenone with 3-chloro-3-methylbut-1-yne in the presence of a catalytic amount of copper(I) iodide. Methylation of 1 afforded O-methyloctandrenolone (2). Oxidation of 2 with m-chloroperoxybenzoic acid followed by hydrolysis gave the racemic trans-(+)-1-(9,10-dihydro-9,10-dihydroxy-5-methoxy-2,2,8, 8-tetramethyl-2H,8H-benzo[1,2-b:3,4-b']dipyran-6-yl)ethanone (3), which confirmed the structure of the natural product previously isolated from Melicope erromangensis.     

紫花前胡中化学成分的研究

采用HP20大孔吸附树脂、ODS、硅胶柱色谱、Sephadex LH-20柱色谱和半制备HPLC等色谱分离手段对紫花前胡的化学成分进行研究。结合理化性质及MS,NMR等谱学数据鉴定化合物的结构,从紫花前胡80%乙醇提取物中分离并鉴定了12个化合物,分别是(9R,10R)-9-acetoxy-8,8-dimethyl-9,10-dihydro-2H,8H-benzo[1,2-b:3,4-b']dipyran-2-one-10-yl ester(1)、补骨脂呋喃香豆精(2)、顺式-3',4'-二千里光酰基-3',4'-二氢邪蒿内酯(3)、(3'R,4'R)-3'-angeloyloxy-4'-senecioyloxy-3',4'-dihydroseselicalipteryxin(4)、(+)-8,9-dihydro-8-(2-hydro-xypropan-2-yl)-2-oxo-2H-furo[2,3h]chromen-9-yl-3-methylbut-2-enoate(5)、libanoridin(6)、丝立尼亭(7)、花椒素(8)、crocatone(9)、peujaponisinol B(10)、peujaponisinol A(11)、ostenol(12)。其中,化合物1~5为首次从当归属植物中分离得到,化合物7~12为首次从紫花前胡中分离得到。     

New naphthopyranone glycosides from Paepalanthus vellozioides and Paepalanthus latipes.

Three new compounds-3, 4-dihydro-10-hydroxy-7-methoxy-3-(R)-methyl-1H-3,4-dihydronaphtho- ]2, 3c]-pyran-1-one-9-O-beta-D-glucopyranoside (1), 3, 4-dihydro-10-hydroxy-7-methoxy-3-(R)-methyl-1H-3,4-dihydronaphtho- [2, 3c]-pyran-1-one-9-O-beta-D-glucopyranosyl-(1-->6)-glucopyranoside (2), and 3,4-dihydro-10-dihydroxy-7-methoxy-3-(R)-methyl-1H-3, 4-dihydronaphtho-[2,3c]-pyran-1-one-9-O-beta-D-allopyranosyl (1-->6)glucopyranoside (3)-were isolated from the leaves of Paepalanthus vellozioides and Paepalanthus latipes and characterized by spectrometric methods, mainly electrospray mass spectrometry and 1D and 2D NMR experiments. These unusual glycosylated dihydronaphthopyranones may serve as taxonomic markers of the genus Paepalanthus, since these compounds were not detected in other genera belonging to the Eriocaulaceae family.     

Cytotoxic 4-phenylcoumarins from the leaves of Marila pluricostata

Bioassay-guided fractionation of the CH(2)Cl(2) extract of the leaves of Marila pluricostata led to the isolation of 17 naturally occurring 4-phenylcoumarins, three of them, 5-hydroxy-8,8-dimethyl-4-phenyl-9,10-dihydro-8H-pyrano-[2,3-f]chromen-2-one (1), 5-hydroxy-8,8-dimethyl-4-phenyl-6-propionyl-9,10-dihydro-8H-pyrano-[2,3-f]chromen-2-one (2), and 5,7-dihydroxy-8-(3-methylbut-2-enyl)-4-phenylchromen-2-one (3), are new natural compounds; the remaining (4-17) are known mammea-type coumarins. Their structures were established by spectroscopic means. All compounds were tested in cytotoxicity assays against the MCF-7, H-460, and SF-268 human cancer cell lines.     

Bioactive secondary metabolites from Boesenbergia pandurata of Myanmar and their preferential cytotoxicity against human pancreatic cancer PANC-1 cell line in nutrient-deprived medium

The chloroform extract of rhizomes of Boesenbergia pandurata demonstrated marked preferential cytotoxicity against human pancreatic PANC-1 cancer cells in nutrient-deprived medium. Bioactivity-directed investigation of this extract yielded four new secondary metabolites, geranyl-2,4-dihydroxy-6-phenethylbenzoate ( 1), 2',4'-dihydroxy-3'-(1'-geranyl)-6'-methoxychalcone ( 2), (1' R,2' S,6' R)-2-hydroxyisopanduratin A ( 3), and (2 R)-8-geranylpinostrobin ( 4), and twenty known compounds ( 5- 24). Among the known compounds, (2 S)-6-geranylpinostrobin ( 5), (+/-)-6-methoxypanduratin A ( 6), and (2 S)-7,8-dihydro-5-hydroxy-2-methyl-2-(4'-methyl-3'-pentenyl)-8-phenyl-2 H,6 H-benzo[1,2- b:5,4- b']dipyran-6-one ( 7) were isolated for the first time from a natural source. The structures of these compounds were elucidated using extensive spectroscopic techniques including CD measurements. All the isolated compounds showed varying degrees of in vitro preferential cytotoxicity against PANC-1 cells. Nicolaioidesin B ( 11) and panduratin A ( 17) were most potent, each showing a PC 100 at 2.5 microM.     

Cytotoxic constituents of the roots of Ekmanianthe longiflora

Bioactivity-directed fractionation of the CHCl(3) extract of the roots of Ekmanianthe longiflora resulted in the isolation of three new natural products, (2R,3R,4R)-3,4-dihydro-3, 4-dihydroxy-2-(3-methyl-2-butenyl)-1(2H)-naphthalenone (1), (2S,3R, 4R)-3,4-dihydro-3, 4-dihydroxy-2-(3-methyl-2-butenyl)-1(2H)-naphthalenone (2), and (2R, 3aR,9R,9aR)-9-hydroxy-2-(1-hydroxy-1-methylethyl)-2,3,3a,4,9 , 9a-hexahydro-naphtho[2,3-b]furan-4-one (3), together with the known compounds 2-(1-hydroxyethyl)naphtho[2,3-b]furan-4,9-quinone (4), 2-acetylnaphtho[2,3-b]furan-4,9-quinone (5), dehydro-iso-alpha-lapachone (6), alpha-lapachone (7), catalponol, and epi-catalponol. The structures of 1-3 were determined using a combination of NMR spectroscopic techniques, and the absolute configurations of compounds 1 and 2 were obtained using Mosher ester methodology. Compounds 4-6 showed significant cytotoxicity in a panel of human cancer cells. alpha-Lapachone (7) exhibited only marginal activity, and catalponol and epi-catalponol were inactive in this regard. When tested at 72 mg/kg/injection in an in vivo mouse P-388 leukemia system, compound 4 was inactive (110% T/C).     

Antiangiogenic activity of synthetic dihydrobenzofuran lignans

A series of synthetic dihydrobenzofuran lignans, obtained by biomimetic oxidative dimerization of caffeic or ferulic acid methyl ester followed by derivatization reactions, was tested for its antiangiogenic activity in the CAM (chorioallantoic membrane) assay. The dimerization product of caffeic acid methyl ester (2a) (methyl (E)-3-[2-(3,4-dihydroxyphenyl)-7-hydroxy-3-methoxycarbonyl-2,3-dihydro-1-benzofuran-5-yl]prop-2-enoate) showed a pronounced antiangiogenic activity, especially the 2R,3R-enantiomer.     

New antioxidant hydroquinone derivatives from the algicolous marine fungus Acremonium sp

A marine fungal isolate, identified as Acremonium sp., was mass cultivated and found to produce two novel hydroquinone derivatives, 7-isopropenylbicyclo[4.2.0]octa-1,3,5-triene-2,5-diol (1) and 7-isopropenylbicyclo[4.2.0]octa-1,3,5-triene-2,5-diol-5-beta-D-glucopyranoside (2). Compound 1 and its glucoside 2 possess a most unusual ring system. The new natural products (3R,4S)-3,4-dihydroxy-7-methyl-3,4-dihydro-1(2H)naphthalenone (3) and (3S,4S)-3,4-dihydroxy-7-methyl-3,4-dihydro-1(2H)-naphthalenone (4) were obtained as a 1:0.8 mixture. 2-(1-Methylethylidene)pentanedioic acid (5) was isolated for the first time as a natural product and its structure proven by X-ray analysis. In addition to these compounds an inseparable mixture of three new isomeric compounds, pentanedioic acid 2-(1-methylethylidene)-5-methyl ester (6), pentanedioic acid 2-(1-methylethylidene)-1-methyl ester (7), and pentanedioic acid 2-(1-methylethenyl)-5-methyl ester (8), was also obtained. Isolated together with the new compounds were three known hydroquinone derivatives, 9, 10, and 11. The structures of all compounds were determined by interpretation of their spectroscopic data (1D and 2D NMR, MS, UV, and IR). Each isolate was tested for its antioxidant properties, and compounds 1 and 9-11 were found to have significant activity.     

娃儿藤内生真菌Talaromyces purpurogenus次生代谢产物研究

通过硅胶柱色谱、中压ODS柱色谱和反相HPLC等多种色谱方法对娃儿藤内生真菌Talaromyces purpurogenus的次生代谢产物进行系统分离,运用NMR,MS,CD和旋光等现代波谱技术进行结构鉴定,共分离鉴定了8个化合物:(R)-2-[5-(methoxycarbonyl)-4-methyl-6-oxo-3,6-dihydro-2H-pyran-2-yl]acetic acid (1),(3S,4R)-3,4-dihydro-3,4-epoxy-5-hydroxynaphthalen-1(2H)-one (2),(-)-mitorubrinol (3),(-)-mitorubrin (4),(±)-asperlone A (5),terreusinone (6),verrucisidinol (7)和cerebroside C (8)。化合物1和2是新化合物。体外抗糖尿病试验结果显示,化合物1在浓度为10μmol·L-1时,对XOD酶的抑制率为69.9%。     

Four new bromotryptamine derivatives from the marine bryozoan Flustra foliacea

Ten brominated alkaloids, 6-bromo-2-(1,1-dimethyl-2-propenyl)-1H-indole-3-carbaldehyde (1), N-(2-[6-bromo-2-(1,1-dimethyl-2-propenyl)-1H-indol-3-yl]ethyl)-N-methylmethanesulfonamide (2), deformylflustrabromine (3), flustrabromine (4), (3aR,8aS)-6-bromo-3a-[(2E)-3,7-dimethyl-2,6-octadienyl]-1,2,3,3a,8,8a-hexahydropyrrolo[2,3-b]-indol-7-ol (5), flustramine C (6), dihydroflustramine C (7), flustramine A (8), flustramine D (9), and flustraminol A (10), and the diterpene 4,6-bis(4-methylpent-3-en-1-yl)-6-methylcyclohexa-1,3-diene-carbaldehyde (11) were isolated from the dichloromethane extract of the North Sea bryozoan Flustra foliacea. Of the 10, four (1, 2, 3, and 5) represent new natural products. The structures of all isolates were elucidated by interpretation of their spectroscopic data (NMR, MS, UV, and IR). For compound 4 complete (13)C NMR data are reported for the first time. Compounds 3 and 6-8 were tested on voltage-activated potassium and sodium channels. Flustramine A (8) shows an unspecific blocking activity on Kv1.4 potassium-mediated currents.     

荨麻抑制前列腺增生作用物质基础研究

通过抑制5α-还原酶、前列腺增生(BPH)大鼠模型,确定二氯甲烷、乙酸乙酯部位为荨麻治疗BPH的活性部位.采用半制备HPLC、NMR等方法,从活性部位中分离、鉴定了28个成分:lobechine methyl ester(1)、邻苯二甲酸二丁酯(2)、亚油酸甘油酯(3)、表松脂酚(4)、羟基二氢博伏内脂(5)、E-7,...     

Biscopyran, a phytotoxic hexasubstituted pyranopyran produced by Biscogniauxia mediterranea, a fungus pathogen of cork oak

A new phytotoxic hexasubstituted pyranopyran, biscopyran (3), was isolated together with phenylacetic acid (2) and previously isolated 5-methylmellein (1) from the liquid culture filtrates of Biscogniauxiamediterranea, a major fungal pathogen involved in oak decline in Sardinia. Biscopyran was characterized by spectroscopic methods as a new (Z)-2-methoxy-1-[7-((Z)-2-methoxybut-2-enoyl)-3,4,5,6-tetramethyl-2H,7H-pyrano[2,3-b]pyran-2-yl]but-2-en-1-one. Biscopyran assayed at 0.26-0.026 mM concentration range caused epinasty on cork oak cuttings. On a nonhost plant, tomato, biscopyran caused wilting. Phenylacetic acid, assayed at the same concentration, was toxic to Q. suber, while on tomato cuttings it induced internal tissue collapse on the stem.     

Trypanocidal and antileishmanial dihydrochelerythrine derivatives from Garcinia lucida

Three benzo[ c]phenanthridine alkaloids have been isolated from the stem bark of Garcinia lucida: dihydrochelerythrine ( 1), 6-acetonyldihydrochelerythrine ( 2), and its new derivative, ( S)1'-(9,10-dihydro-2',3'-dihydroxy-7,8-dimethoxy-10-methyl-1,2-benzophenanthridin-9-yl)propan-2'-one (lucidamine A) ( 3). The new diisoprenylated derivative of lucidamine B ( 4) was obtained by semisynthesis. These dihydrochelerythrine derivatives as well as the crude extract displayed attractive antiprotozoal activity against Trypanosoma brucei brucei and Leishmania donovani, with little toxicity to Vero cells and the host cells. This is the first trypanocidal and antileishmanial bioguided study of G. lucida, and the activity of the crude extract as well as of the dihydrochelerythrine derivatives are reported for the first time.     

Phelligridins C-F: cytotoxic pyrano[4,3-c][2]benzopyran-1,6-dione and furo[3,2-c]pyran-4-one derivatives from the fungus Phellinus igniarius

Three unique pyrano[4,3-c][2]benzopyran-1,6-dione derivatives and a new furo[3,2-c]pyran-4-one, named phelligridins C-F (2-5), together with hispolon (8), (E)-4-(3,4-dihydroxyphenyl)but-3-en-2-one (9), 4-hydroxybenzaldehyde, protocatechualdehyde, syringic acid, protocatechuic acid, caffeic acid, isoergosterone, and octadecyl ferulate were isolated and identified from the ethanolic extract of Phellinus igniarius. Their structures were determined by spectroscopic methods including IR, MS, and 1D and 2D NMR experiments. The structures of the new compounds were characterized as 3-(4-hydroxystyryl)-8,9-dihydroxypyrano[4,3-c]isochromene-4-one (2), 3-(3,4-hydroxystyryl)-8,9-dihydroxypyrano[4,3-c]isochromene-4-one (3), 8,9-dihydroxy-3-[5',6'-dihydroxy-5' '-methyl-3' '-oxo-spiro[fural-2' '(3' 'H),1'-indene]-2'-yl]-1H,6H-pyrano[4,3-c][2]benzopyran-1,6-dione (4), and (3Z)-3-(3,4-dihydroxybenzylidene)-6-(3,4-dihydroxystyryl)-2,3-dihydro-2-methoxy-2-(2-oxo-propyl)furo[3,2-c]pyran-4-one (5), respectively. Some compounds including 2 and 3 showed in vitro selective cytotoxicity against a human lung cancer cell line (A549) and a liver cancer cell line (Bel7402). Possible biogenetic sequences to the formation of 1-9 are postulated.     

A new naphthopyrone derivative from Cassia quinquangulata and structural revision of quinquangulin and its glycosides

A novel naphthopyrone derivative, named quinquangulone (1), has been isolated from Cassia quinquangulata, along with the known compounds quinquangulin (2) and its two glycosides (3 and 4), rubrofusarin (5) and its two glycosides (6 and 7), nor-rubrofusarin (8) and its 6-O-glucoside (9), and three stilbenes (10-12). The structure of quinquangulone was established by spectral interpretation as 5,9-dihydroxy-8-methoxy-2,9-dimethyl-6-oxo-4H,6H,9H-naphtho-[2,3-b]pyran-4-one. Reinvestigation of the NMR spectra of quinquangulin led to revision of its structure as 5,6-dihydroxy-8-methoxy-2,9-dimethyl-4H-naphtho[2,3-b]pyran-4-one (2a). The structures of two quinguangulin glycosides, 3 and 4, were also revised accordingly. Compound 2a exhibited activity against Staphylococcus aureus and methicillin-resistant S. aureus (MIC, 3.125 and 6.25 microg/mL, respectively).     

Benzoic acid derivatives, acetophenones, and anti-inflammatory constituents from Melicope semecarpifolia

Two new benzoic acid derivatives, (E)-3-acetyl-6-(3,7-dimethylocta-2,6-dienyloxy)-2,4-dihydroxybenzoic acid (1) and (E)-3-acetyl-4-(3,7-dimethylocta-2,6-dienyloxy)-2,6-dihydroxybenzoic acid (2), and three new acetophenones, (E)-1-(5-(3,7-dimethylocta-2,6-dienyloxy)-7-hydroxy-2,2-dimethyl-2 H-chromen-8-yl)ethanone (3), (E)-1-(5-(3,7-dimethylocta-2,6-dienyloxy)-7-hydroxy-2-methyl-2-(4-methylpent-3-enyl)-2 H-chromen-8-yl)ethanone (4), and (R,E)-1-(5-(3,7-dimethylocta-2,6-dienyloxy)-3,7-dihydroxy-2,2-dimethylchroman-8-yl)ethanone (5), have been isolated from the fruits of Melicope semecarpifolia, together with eight known compounds. The structures were determined through in-depth NMR and mass spectrometric analyses. Among the isolated compounds, 2-(1'-geranyloxy)-4,6,beta-trihydroxyacetophenone (8), 4-(1'-geranyloxy)-2,6,beta-trihydroxyacetophenone (9), 5-hydroxy-3,7,3',4'-tetramethoxyflavone (10), 5,4'-dihydroxy-3,7,3'-trimethoxyflavone (11), and 5,4'-dihydroxy-3,7-dimethoxyflavone (12) exhibited potent inhibition (IC50<4 microg/mL) on superoxide anion generation and elastase release by human neutrophils in response to fMet-Leu-Phe/cytochalasin B.     

Kutznerides 1-4, depsipeptides from the actinomycete Kutzneria sp. 744 inhabiting mycorrhizal roots of Picea abies seedlings

Bioassay-guided fractionation of culture supernatants of the actinomycete Kutzneria sp. 744 resulted in the isolation of four new depsipeptides (1-4). Structure analysis revealed the general structure: cyclo[2-(1-methylcyclopropyl)-D-glycine-(2S,3aR,8aS)-6,7-dichloro-3a-hydroxy-1,2,3,3a,8,8a-hexahydropyrrolo[2,3-b]indole-2-carboxylic acid-3-hydroxy-D-glutamic acid-O-methyl-L-serine-L-piperazic acid-(S)-2-hydroxy-3,3-dimethylbutanoic acid]. The 3-hydroxy-d-glutamic acid was present as its threo-isomer in 1 and 2 and as its erythro-isomer in 3 and 4. The piperazic acid was modified to its (R)-4-chloro analogue in 2 and to its C-5/N unsaturated analogue in 4. Compounds 1-4 displayed moderate spore germination inhibiting activity against several common root-rotting fungi.     

喜树中两个DNA拓扑异构酶Ⅰ抑制剂

目的：以生物活性为向导在喜树中寻找天然的DNA拓扑异构酶Ⅰ抑制剂。方法：用各种层析方法和波谱方法从喜树中分离并鉴定了14个化合物。结果：其结构分别鉴定为喜树碱(1)，肌醇(2)，喜果苷(3)，3’甲基3，4O，O-亚甲基鞣花酸-4’-D-β-D-吡喃葡萄糖苷(4)，2-氧-1，2-二氢．喹啉4酸(5)，马钱子酸(6)，4-甲基-1，2-环己烷二甲醇(7)，strictosamide(8)，獐芽菜苷(9)，乙酰胺(10)，氯原酸(11)，strictosidinic acid(12)，1-咖啡酰基奎宁酸(13)和10-羟基喜树碱(14)。结论：化合物4-13为首次从该植物中分得，化合物4的核磁数据在文献中有误，本文对其进行了重新归属。经体外活性测试，化合物1对DNA拓扑异构酶Ⅰ有中等程度的抑制作用，化合物4，14对DNA拓扑异构酶Ⅰ有强的抑制作用。     

Studies directed toward the synthesis of cryptoheptine

Synthesis of 5,10-dihydro-10-methylindolo[3, 2-b][1]benzazepin-12(11H)-one (2), an isomer of the reported structure for cryptoheptine (1), is presented. Attempts to convert 2 to 1 led to 10-methylindolo[3,2-b][1]benzazepin-12-one (10), an oxidation product of 2 and presumably 1. These results highlight the potential instability of cryptoheptine and cast doubt on its proposed structure.     

Kinmoonosides A-C, three new cytotoxic saponins from the fruits of Acacia concinna, a medicinal plant collected in myanmar

Three genuine saponins, named kinmoonosides A-C (1-3), have been isolated, together with a new monoterpenoid (4), from a methanolic extract of the fruits of Acacia concinna. The structures of kinmoonosides A-C were elucidated on the basis of spectral analysis as 3-O-?alpha-L-arabinopyranosyl(1-->6)-[beta-D-glucopyranosyl(1-->2) ]-b eta-D-glucopyranosyl?-21-O-?(6R, 2E)-2-hydroxymethyl-6-methyl-6-O-[4-O-(2'E)-6'-hydroxyl-2'-hydroxymet hyl-6'-methyl-2',7'-octadienoyl-beta-D-quinovopyranosyl]-2, 7-octadienoyl?acacic acid 28-O-alpha-L-arabinofuranosyl(1-->4)-[beta-D-glucopyranosyl(1-->3)]-a lpha-L-rhamnopyranosyl(1-->2)-beta-D-glucopyranosyl ester (1); 3-O-?alpha-L-arabinopyranosyl(1-->6)-[beta-D-glucopyranosyl(1-->2) ]-b eta-D-glucopyranosyl?-21-O-?(6S, 2E)-2-hydroxymethyl-6-methyl-6-O-[4-O-(2'E)-6'-hydroxyl-2'-hydroxymet hyl-6'-methyl-2',7'-octadienoyl-beta-D-quinobopyranosyl]-2, 7-octadienoyl?acacic acid 28-O-alpha-L-arabinofuranosyl(1-->4)-[beta-D-glucopyranosyl(1-->3)]-a lpha-L-rhamnopyranosyl(1-->2)-beta-D-glucopyranosyl ester (2); and 3-O-?alpha-L-arabinopyranosyl(1-->6)-[beta-D-glucopyranosyl(1-->2) ]-b eta-D-glucopyranosyl?-21-O-[(2E)-6-hydroxyl-2-hydroxymethyl-6-methyl- 2,7-octadienoyl]acacic acid 28-O-alpha-L-arabinofuranosyl(1-->4)-[beta-D-glucopyranosyl(1-->3)]-a lpha-L-rhamnopyranosyl(1-->2)-beta-D-glucopyranosyl ester (3), respectively. The new monoterpenoid 4 was determined as 4-O-[(2E)-6-hydroxyl-2-hydroxymethyl-6-methyl-2, 7-octadienoyl]-D-quinovopyranose. Compounds 1-3 showed significant cytotoxicity against human HT-1080 fibrosarcoma cells.