Starfish saponins, 48. Isolation of fifteen sterol constituents (six glycosides and nine polyhydroxysteroids) from the starfish Solaster borealis.

This paper reports a complete steroid glycoside and polyhydroxysteroid analysis of the starfish Solaster borealis, collected at Mutsu Bay, Japan. The glycosides include a new pentaglycoside steroid sulfate ("asterosaponin"), designated solasteroside A [1], two new sulfated 24-O-diglycosides, both with the common 5 alpha-cholesta-3 beta,6 alpha,8,15 alpha, 24-pentaol aglycone, borealosides A [2] and B [3], two new 24-O-(3-O-methyl)xylosides, borealosides C [4] and D [5], having the same aglycone with an additional hydroxy group at 4 beta-position in 5, and the known amurensoside B, previously isolated from Asterias amurensis. Among the polyhydroxysteroid constituents, four (7-10) are new, and five (11-15) have previously been isolated from starfishes.     

Synthesis of ellagic acid O-alkyl derivatives and isolation of ellagic acid as a tetrahexanoyl derivative from Fragaria ananassa.

Ellagic acid [1] is a gallic acid dimer that occurs in plants, fruits, and nuts, either in its free form, or in a series of ellagitannins, or as a glucoside. It has been shown to inhibit cancer induced by several types of chemical carcinogens including polycyclic aromatic hydrocarbons, N-nitrosamines, aflatoxin, and aromatic amines. It has been extracted from a number of fruits, including strawberries; however, its presence in the extracts was determined only by hplc connected with a diode array detector. In the present report, ellagic acid was isolated as a tetrahexanoyl derivative 2 from Fragaria ananassa and identified by 13C and 1H nmr and ms. The 13C-nmr shifts of the aromatic carbons adjacent to a hexanoyloxy group were assigned using two new synthetic model compounds: 3,3'-dihexanoyloxydiphenic-2,2',6,6'-dilactone [3] and 4,4'-dihexanoyloxydiphenic-2,2',6,6'-dilactone [4]. Two new derivatives of ellagic acid [1],3,3'-di-beta-D-glucopyranosylellagic acid decaacetate [5] and 3,3'-di-n-octyl-4,4'-dihexanoylellagic acid [7], were also synthesized. Both derivatives were less effective as inhibitors of benzo[a]pyrene tumorigenesis in the lungs of strain A/J mice than ellagic acid.     

Kinetic study of littorine rearrangement in Datura innoxia hairy roots by (13)C NMR spectroscopy

The kinetics of tropane alkaloid biosynthesis, particularly the isomerization of littorine into hyoscyamine, were studied by analyzing the kinetics of carbon-13 ((13)C) in metabolites of Datura innoxia hairy root cultures fed with labeled tropoyl moiety precursors. Both littorine and hyoscyamine were the major alkaloids accumulated, while scopolamine was never detected. Feeding root cultures with (RS)-phenyl[1,3-(13)C(2)]lactic acid led to (13)C spin-spin coupling detected on C-1' and C-2' of the hyoscyamine skeleton, which validated the intramolecular rearrangement of littorine into hyoscyamine. Label from phenyl[1-(13)C]alanine or (RS)-phenyl[1,3-(13)C(2)]lactic acid was incorporated at higher levels in littorine than in hyoscyamine. Initially, the apparent hyoscyamine biosynthesized rate (v(app)()hyo = 0.9 micromol (13)C.flask(-1).d(-1)) was lower than littorine formation (v(app)()litto = 1.8 micromol (13)C.flask(-1).d(-1)), suggesting that the isomerization reaction could be rate limiting. The results obtained for the kinetics of littorine biosynthesis were in agreement with the role of this compound as a direct precursor of hyoscyamine biosynthesis.     

Characterization and feeding deterrent effects on the aphid, Schizaphis graminum, of some derivatives of the sweet compounds, stevioside and rebaudioside A

The intensely sweet compounds, stevioside [1] and rebaudioside A [2], and 15 of their derivatives, were tested for feeding deterrent activity against the aphid, Schizaphis graminum. Included with these compounds was steviol [4], the aglycone of stevioside and rebaudioside A that was one of the most active compounds in this investigation. Loss of feeding deterrent activity of steviol was observed on acetylation or glycosylation of the C-13 tertiary hydroxy group or on methylation of the C-19 carboxylic acid substituent. In contrast, the antifeedant activity of steviol was not greatly affected by modification of either the C-16 exomethylene group or the C/D-ring junction stereochemistry. 13C-nmr data have been obtained for 12 of the test compounds investigated.     

Antitumor agents, 119. Kansuiphorins A and B, two novel antileukemic diterpene esters from Euphorbia kansui

The extract of the roots of Euphorbia kansui, which has been widely used in Chinese folk medicine for the treatment of cancer, demonstrated antileukemic activity against the P-388 lymphocytic leukemia in mice. Bioassay-directed fractionation of the active extract led to the isolation and characterization of two novel antileukemic diterpene esters, kansuiphorin A [1] [13-hydroxyingenol-3-(2,3-dimethylbutanoate)-13-dodecanoate- 20- hexadecanoate] and kansuiphorin B [2] [6,7-epoxy-13-hydroxyingenol-3-(2,3-dimethylbutanoate)-13-do decanoate-20- hexadecanoate], whose structures were established from spectral evidence and chemical transformation. Kansuiphorins A and B demonstrated potent antileukemic activity with T/C greater than or equal to 176 and 177% at 0.1 and 0.5 mg/kg, respectively. The selectivity of kansuiphorin A, which inhibits the growth of particular cell types within the disease-oriented human cancer cell line panels, is discussed.     

Studies on iridoids of tissue cultures of Penstemon serrulatus: isolation and their antiproliferative properties.

Penstemide and serrulatoloside as well as penstemide aglycone and serrulatoloside aglycone were isolated and identified in the calli and suspension cultures of Penstemon serrulatus. The influence of serrulatoloside, penstemide, and its aglycone on the spontaneous proliferation of mouse spleen lymphocytes or hepatoma cells in the Syrian hamster has been estimated in vitro. It has been found that these compounds produce a dose-dependent inhibition of [3H]-thymidine incorporation into the DNA of the examined cells.     

Dioxapyrrolomycin biosynthesis in Streptomyces fumanus

Streptomyces fumanus, intramurally coded as culture LL-F42248, produces a series of pyrrolomycins including dioxapyrrolomycin (1) as the principal component. Our biosynthetic studies revealed that feeding labeled acetate to growing cultures of S. fumanus yielded pyrrolomycins labeled in the phenyl ring only. When l-[methyl-13C]methionine was fed, the labeled carbon atom was found in the methoxy group of pyrrolomycins H-J and in the methylenedioxy bridge of dioxapyrrolomycin. A Na15NO3-enriched medium was employed to produce 15N-labeled pyrrolomycins in which both nitrogen atoms were highly enriched, whereas feeding of 15N-labeled l-proline furnished pyrrolomycins labeled in the pyrrole moiety. Thus, S. fumanus elaborates the pyrrolomycin skeleton from proline and a polyketide precursor. Since the organism readily converted 13C- or 15N-labeled pyrrolomycin C, G, or H into the correspondingly labeled dioxapyrrolomycin, these minor pyrrolomycins are actually precursors of the ultimate product, dioxapyrrolomycin.     

Stevisalioside A, a novel bitter-tasting ent-atisene glycoside from the roots of Stevia salicifolia.

A new acetylated ent-atisene glycoside, stevisalioside A [1], has been isolated as a bitter-tasting principle from Stevia salicifolia roots. The structure was established by the interpretation of spectral data, with the nmr assignments of this compound being based on 1H-1H COSY, 1H-13C HETCOR, and selective INEPT experiments. A rearrangement product 4 of the aglycone moiety obtained by alkaline hydrolysis supported the structure of 1. This is the first report of the occurrence of an atisane-type diterpene from the genus Stevia.     

Unusual C25 steroid isomers with bicyclo[4.4.1]A/B rings from a volcano ash-derived fungus Penicillium citrinum

Eleven new unusual C25 steroid isomers with bicyclo[4.4.1]A/B rings, 24- epi-cyclocitrinol (1), 20-O-methyl-24-epi-cyclocitrinol (3), 20-O-methylcyclocitrinol (4), 24-oxocyclocitrinol (7), 12 R-hydroxycyclocitrinol (8), neocyclocitrinols B (10) and D (12), erythro-23-O-methylneocyclocitrinol (13), threo-23-O-methylneocyclocitrinol (14), isocyclocitrinol B (15), and precyclocitrinol B (18), and five known steroids, cyclocitrinol (2), neocyclocitrinols A (9) and C (11), isocyclocitrinol A (16), and 22-O-acetylisocyclocitrinol A (17), were characterized from cultures of the volcanic ash-derived fungus Penicillium citrinum HGY1-5. Their structures and absolute configurations were established by spectroscopic and chemical methods together with X-ray diffraction analysis. Compounds 3, 4, and 10- 14 were determined to be artifacts on the basis of acidic transformation of 1- 4. The biosynthetic origin of these steroids derived from ergosterol was investigated by feeding (13)C-labeled acetates to the growing cultures of P. citrinum HGY1-5. The biological activities of all 16 steroids were tested using the cAMP assay on GPR12-CHO and WT-CHO cells. The results showed that compounds 1, 2, 10, 11, and 14 could induce the production of cAMP in GPR12-transfected CHO cells.     

New phenolic glucosides from the leaves of Eurya tigang.

Three new compounds, 6'-O-coumaroyl-1'-O-[2-(4-hydroxyphenyl)ethyl]-beta-D-glucopyra nos ide [1] (eutigoside A), 6'-O-coumaroyl-1'-O-[2-(1-hydroxy-4-oxo-2,5-cyclohexadien-1- yl)ethyl]-beta-D-glucopyranoside [2] (eutigoside B), and 6'-O-cinnamoyl-1'-O-[2-(1-hydroxy-4-oxo-2,5-cyclohexadien-1-yl)eth yl]- beta-D-glucopyranoside [3] (eutigoside C) have been isolated from the leaves of Eurya tigang, along with other known compounds (afzelin, quercitrin, p-coumaric acid, methyl-alpha-D-fructofuranoside, isorengyol, and euryanoside). Their structures were determined by chemical and spectroscopic methods (uv, ir, ms, 1H-1H COSY, and 1H-13C COSY).     

Durhamycin A,a potent inhibitor of HIV Tat transactivation

Tat is a small HIV protein essential for both viral replication and the progression of HIV disease. In our efforts to discover Tat inhibitors from natural product screening of microbial fermentation extracts, we discovered durhamycin A (1) as a potent inhibitor (IC(50) = 4.8 nM) of Tat transactivation. Detailed NMR and MS/MS studies were utilized to elucidate the structure of 1 as a new member of the aureolic acid family of antibiotics. It consists of tetrasaccharide and disaccharide moieties attached to the aglycone, which is hitherto unknown in the aureolic acid family. Three other novel analogues, durhamycin B (2), compound (3), and the aglycone (4), were also discovered or chemically prepared that were less potent than durhamycin A.     

大高良姜的化学成分研究

目的：对大高良姜的根茎部位化学成分进行系统研究。方法：采用硅胶和Sephadex LH-20柱色谱等手段进行分离纯化，运用UV、IR、^1H—NMR13C—NMR、MS等谱学方法进行结构鉴定。结果：共分离鉴定了11个化合物，分别为4-[（E）-3-hydroxyprop-1-enyl]phenylacetate（1），反式对羟基桂皮醛乙酯（2），5-hydroxy-7-（4″-hydroxy-3″-methoxyphenyl）-1-phenyl-3-heptanone（3），7-（4″-hydroxy-3″-methoxy—phenyl）-1-phenylhep-4-en-3-one（4），[1′S]-1′-乙酰氧丁香酚乙酯（5），反式对羟基桂皮醛（6），对羟基苯甲醛（7），1-（4-hydroxyphenyl）propan．1-one（8），高良姜素（9），trans—P—coumaryl diacetate（10），β-谷甾醇（11）。结论：化合物1是首次从自然界分离得到的天然产物，化合物2为首次从该属植物中分离得到的苯丙素类化合物，化合物3和4是首次从该种植物中分离得到的双苯庚烷类化合物。     

Homoscalarane sesterterpenes from Lendenfeldia frondosa.

The marine sponge Lendenfeldia frondosa, collected from the Solomon Islands, has yielded homoscalarane sesterterpenes. Two new metabolites, epihomoscalaralactone IIA [5] and homoscalarate II [10], were accompanied by two known metabolites, homoscalaralactone IIA [1] and homoscalaralactone IIB [7]. These structures were established by analysis of 2D nmr data, trends in 13C-nmr shifts, and comparison of experimental with molecular-mechanics-calculated nmr J's. Each of the alcohols 1, 2, and 3 was converted to its corresponding acetate, 2, 6, and 8, respectively. Compound 6 exhibited moderate anti-inflammatory activity.     

Trisphaerolide A,a novel polyketide from the Dominican sponge Erylus trisphaerus

The structure of trisphaerolide A (1), a mildly cytotoxic metabolite isolated from extracts of the marine sponge Erylus trisphaerus collected in Dominica, has been elucidated by detailed analysis of spectroscopic data. Trisphaerolide A (1) has a putative polyketide biogenesis, incorporating a rare variant on the standard pathway, which involves the addition of methyl branches arising from C-2 carbons of acetate units to chain carbons that arise from C-1 of acetate units.     

东北剌人参挥发油化学成分分析

[目的]获得东北刺人参挥发油化学成分信息。[方法]采用水蒸气蒸馏法提取东北刺人参挥发油,将挥发油分成极性不同的两部位,分别用气相色谱-质谱联用仪（GC—MS）技术对这两部位化学成分进行分析比较。[结果]从东北刺人参挥发油乙醚（A）部位分离出了31个成分,鉴定了其中20个化合物,占挥发油总量的92．72％;挥发油乙酸乙酯（B）部位分离出了18个成分,鉴定了13个成分,占挥发油总量的91．66％。[结论]该实验挥发油得油率高,GC—MS方法简便、快速。     

Biosynthesis of scorpinone, a 2-azaanthraquinone from Amorosia littoralis, a fungus from marine sediment

The biogenetic origin of the carbon atoms in the 2-azaanthraquinone scorpinone ( 1), produced by the rare fungus Amorosia littoralis isolated from marine sediment, was explored through isotopic enrichment studies utilizing [2- (13)C]-acetate and [1,2- (13)C]-acetate. The labeling results reveal a heptaketide precursor is involved in the biosynthesis of 1, as has been found for the structurally related naphthoquinone dihydrofusarubin. The previously identified naphthoquinone herbarin ( 2) was also isolated and appears to bear the same biogenetic relationship to 1 as the fusarubins do to the fungal 2-azaanthraquinone bostrycoidins.     

Evidence for an NIH shift as the origin of the apparently anomalous distribution of deuterium in estragole from Artemisia dracunculus

Feeding experiments of [2-(2)H]- and [4'-(2)H]phenylalanine in Artemisia dracunculus validate the hypothesis that the marked difference in deuterium content at the natural abundance level between the aromatic carbons of estragole (1) is due to an NIH shift during the hydroxylation of the benzene ring.     

Biosynthesis of chloroplastidic and extrachloroplastidic terpenoids in liverwort cultured cells: 13C serine as a probe of terpene biosynthesis via mevalonate and non-mevalonate pathways

Two terpenoid biosynthetic pathways, the mevalonate and non-mevalonate (glyceraldehyde phosphate-pyruvate) routes, were examined by feeding (13)C-labeled serines ([1-(13)C]- and [3-(13)C]-) to the cultured cells of the liverwort, Heteroscyphus planus. The labeling patterns observed in the isoprenoid unit of the biosynthetically (13)C-labeled stigmasterol corresponded to those expected from the mevalonate pathway, while those of the phytyl side chain corresponded to those from the non-mevalonate pathway. Thus, serine is a potential probe to determine the origin of terpenoid biosynthesis, in either the mevalonate or non-mevalonate pathway.     

p-hydroxyacetophenone amides from Cystobacter ferrugineus, strain Cb G35

A family of six novel p-hydroxyacetophenone amides, 1-6, was isolated from Cystobacter ferrugineus, strain Cb G35. Their structures were elucidated by ESI-TOF mass spectrometry and NMR spectroscopy. Feeding experiments with labeled [13C?,1?N]-tyrosine and [d??]-leucine identified the biosynthetic precursors of 1.     

Bioactive neolignans from Endlicheria dysodantha.

From bioactivity-directed fractionation of the EtOH extract of Endlicheria dysodantha, dysodanthin A and dysodanthin B, which are new hexahydrobenzofuranoid neolignans, have been isolated. In addition, the known neolignans, compound 4, which is a burchellin analogue, and megaphone acetate [1] were isolated. All four neolignans showed activities in the brine shrimp lethality test; compounds 1-3 also inhibited the growth of crown gall tumors on potato discs and were cytotoxic to human tumor cells in culture. This is the first report of these neolignans isolated from the genus Endlicheria and of their completely assigned 1H-and 13C-nmr data.