Resin glycosides from the flowers of Ipomoea murucoides

The CHCl(3)-soluble extract from the flowers of the Mexican medicinal plant Ipomoea murucoides, through preparative-scale recycling HPLC, yielded murucoidins I-V (1-5), which are new pentasaccharides of jalapinolic acid, as well as the known stoloniferin I (6). Saponification of the crude resin glycoside mixture yielded two glycosidic acids, simonic acid B (9) and operculinic acid A (10), and their esterifying residues were composed of the two short-chain fatty acids, 2-methylpropanoic and (2S)-methylbutyric acids. All the isolated compounds (1-6) were characterized through high-field NMR spectroscopy. Compound 4 exhibited marginal cytotoxicity against Hep-2 cells (ED(50) 4 microg/mL).     

Profiling of the resin glycoside content of Mexican jalap roots with purgative activity

Mexican Jalap roots, a prehispanic medicinal plant complex still considered to be a useful laxative, can be found as an ingredient in some over-the-counter products sold by herbalists in contemporary Mexico. The drug is prepared from the dried roots of several morning glories, all of which have been identified as members of the genus Ipomoea. Analysis of several commercial samples was assessed by generating HPLC and 13C NMR spectroscopic profiles of the glycosidic acids obtained through saponification of the resin glycoside contents. These profiles distinguish the three Mexican jalaps currently in frequent use and can serve as analytical tools for the authentication and quality control of these purgative herbal drugs. Ipomoea purga, the authentic "jalap root", yielded two new hexasaccharides of convolvulinic and jalapinolic acids, purgic acids A (1) and B (2), respectively. Scammonic acid A (3), a tetrasaccharide, was produced from Ipomoea orizabensis, the Mexican scammony or false jalap. Operculinic acid B (4), a pentasaccharide, was identified in Ipomoea stans. Semipreparative HPLC was performed to obtain pure samples of new compounds 1 and 2 in sufficient quantity to elucidate their structure by high-field NMR spectroscopy. Purgic acid A (1) was identified as (11S)-hydroxytetradecanoic acid 11-O-beta-D-quinovopyranosyl-(1-->2)-O-beta-D-glucopyranosyl-(1-->3)-O-[beta-D-fucopyranosyl-(1-->4)]-O-alpha-L-rhamnopyranosyl-(1-->2)-O-beta-D-glucopyranosyl-(1-->2)-O-beta-D-quinovopyranoside, while purgic acid B (2) was characterized with (11S)-hydroxyhexadecanoic acid as its aglycon but having the same glycosidation sequence in the oligosaccharide core.     

Characterization of lipophilic pentasaccharides from beach morning glory (Ipomoea pes-caprae)

The hexane-soluble extract from the aerial parts of the herbal drug Ipomoea pes-caprae (beach morning-glory), through preparative-scale recycling HPLC, yielded six lipophilic glycosides, namely, five new pentasaccharides of jalapinolic acid, pescaproside A (1) and pescapreins I-IV (2-5), as well as the known stoloniferin III (6). Saponification of the crude resin glycoside mixture yielded simonic acid B (7) as the glycosidic acid component, whereas the esterifying residues of the natural oligosaccharides comprised five fatty acids: 2-methylpropanoic, (2S)-methylbutyric, n-hexanoic, n-decanoic, and n-dodecanoic acids. Pescaproside A (1), an acylated glycosidic acid methyl ester, is related structurally to the product obtained from the macrolactone hydrolysis of pescapreins I-IV (2-5). All the isolated compounds (1-6), characterized through high-field NMR spectroscopy, were found to be weakly cytotoxic to a small panel of cancer cell lines.     

Intrapilosins I-VII, pentasaccharides from the seeds of Ipomoea intrapilosa

Purification of a CHCl3-soluble extract from seeds of the Mexican medicinal arborescent morning glory, Ipomoea intrapilosa, by means of preparative-scale recycling HPLC, yielded seven new resin glycosides, intrapilosins I-VII (1-7). Their structures were established through the interpretation of their NMR spectroscopic and FABMS data. All pentasaccharides were found to be macrolactones of the known operculinic acid A with different fatty acids esterifying the same positions: C-2 on the second rhamnose unit and C-3 and C-4 on the third rhamnose moiety. The lactonization site of the aglycon could be placed at C-2 of the second saccharide. The fatty acid components of 1-7 were identified as (+)-(2S)-methylbutanoic, octanoic (caprylic), dodecanoic (lauric), and trans-cinnamic. The less common (-)-(2R)-methylbutanoic acid was also isolated as one of the saponification-liberated residues from intrapilosin IV (4). The presence of the (2R)- and (2S)-methylbutanoyl enantiomers bonded to the same oligosaccharide core in intrapilosins IV (4) and V (5) represents an example of diastereoisomerism due to a chiral esterifying moiety in the resin glycoside mixtures of a morning glory species.     

Inhibitors of bacterial multidrug efflux pumps from the resin glycosides of Ipomoea murucoides

A reinvestigation of the CHCl 3-soluble extract from flowers of the Mexican medicinal arborescent morning glory, Ipomoea murucoides, through preparative-scale recycling HPLC, yielded six new pentasaccharides, murucoidins VI-XI (1- 6), as well as the known pescaprein III (7), stoloniferin I (8), and murucoidins I-V (9- 13). Their structures were characterized through the interpretation of their NMR spectroscopic and FABMS data. Compounds 1-6 were found to be macrolactones of three known glycosidic acids identified as simonic acids A and B, and operculinic acid A, with different fatty acids esterifying the same positions, C-2 on the second rhamnose unit and C-4 on the third rhamnose moiety. The lactonization site of the aglycone was placed at C-2 or C-3 of the second saccharide unit. The esterifying residues were composed of two short-chain fatty acids, 2-methylpropanoic and (2S)-methylbutyric acids, and two long-chain fatty acids, n-dodecanoic (lauric) acid and the new (8R)-(-)-8-hydroxydodecanoic acid. For the latter residue, its absolute configuration was determined by analysis of its Mosher ester derivatives. All members of the murucoidin series exerted a potentiation effect of norfloxacin against the NorA overexpressing Staphylococcus aureus strain SA-1199B by increasing the activity 4-fold (8 microg/mL from 32 microg/mL) at concentrations of 5-25 microg/mL. Stoloniferin I (8) enhanced norfloxacin activity 8-fold when incorporated at a concentration of 5 microg/mL. Therefore, this type of amphipathic oligosaccharide could be developed further to provide more potent inhibitors of this multidrug efflux pump.     

Cytotoxic constituents of the twigs and leaves of Aglaia rubiginosa

Activity-guided fractionation of a CHCl(3)-soluble extract of the twigs of Aglaia rubiginosa, using human oral epidermoid carcinoma (KB) cells as a monitor, led to the isolation of a new naturally occurring cyclopenta[b]benzofuran, 1-O-acetylrocaglaol (1), along with seven known compounds, methyl rocaglate (2), rocagloic acid (3), 1-O-acetylmethyl rocaglate (4), desyclamide, eryodictiol, 5-hydroxy-3,7,4'-trimethoxyflavone, and naringenin. A CHCl(3) extract of the leaves of A. rubiginosa yielded the new compound (3S,4R,22R)-cholest-7,24-diene-3,4,22-triol (5), as well as 11 known compounds, including 2 and 4 and cabraleone, dammarelonic acid, (20S,23E)-20,25-dihydroxy-3,4-secodammara-4(28),23-dienoic acid, (20S,23E)-20,25-dihydroxy-3,4-secodammara-4(28),23-dienoic acid methyl ester, (3beta,4beta,22R)-ergosta-5,24(24')-diene-3,4,22-triol, ocotillone, shoreic acid, beta-sitosterol, and beta-sitosterol glycoside. The structures of 1 and 5 were elucidated by spectral and chemical methods. Isolates were evaluated with a human cancer cell panel, and compounds 1-4 were found to exhibit potent cytotoxic activity.     

Resin glycosides from the herbal drug jalap (Ipomoea purga)

Three new resin glycosides, purginosides I and II (1 and 2) and purgin I (3), were isolated from the aerial parts of Ipomoea purga and purified by preparative-scale recycling HPLC from a chloroform-soluble extract. Their structures were established through NMR spectroscopy and mass spectrometry. Purginosides I and II (1 and 2) are partially acylated branched pentasaccharides derived from operculinic acid A, which is composed of one D-fucose, one D-glucose, and three l-rhamnose units. The site of the aglycon macrolactonization is at C-2 of the second saccharide (rhamnose). In both compounds 1 and 2, three different esterifying residues were located at C-2 of the second rhamnose unit and at C-2 (or C-3) and C-4 on the third rhamnose moiety. The acylating residues were characterized as trans-cinnamic, n-decanoic, and either (+)-(2S)-2-methylbutanoic or n-hexanoic acid. Purgin I (3) was found to be an ester-type dimer of operculinic acid A, acylated by n-dodecanoic, (+)-(2S)-2-methylbutanoic, and trans-cinnamic acids at the same oligosaccharide core positions found in compounds 1 and 2. The site of lactonization by the aglycon in unit A was placed at C-2 of the second saccharide. The position for the ester linkage for the monomeric unit B on the macrocyclic unit A was identified as C-4 of the terminal glucose. This is the first report on the isolation, purification, and structure elucidation of intact individual resin glycoside constituents from the herbal drug jalap.     

Four cycloartane triterpenoids and six related saponins from Passiflora edulis

Four cycloartane triterpenes, cyclopassifloic acids A (1), B (2), C (3), and D (4), and six related saponins, cyclopassiflosides I (5), II (6), III (7), IV (8), V (9), and VI (10), were isolated from the leaves and stems of Passiflora edulis, and their structures were elucidated on the base of extensive NMR experiments and chemical methods. Cyclopassifloic acids A-D were assigned as 22(R), 24(S)-1alpha,3beta,22,24,31-pentahydroxy-24-methylcycloartan -28-oic acid; 24(S)-1alpha,3beta,24, 31-tetrahydroxy-24-methylcycloartan-28-oic acid; 20(S),24(S)-1alpha, 3beta,21,24,31-pentahydroxy-24-methylcycloartan-28-oic acid; and 22(R)-1alpha,3beta,22-trihydroxy-24-oxocycloartan-28-oic acid, respectively. Cyclopassiflosides I-VI, in turn, were established as the 28-O-beta-D-glucopyranosides of cyclopassifloic acids A-D. Finally, cyclopassiflosides III and V were demonstrated as the 28, 31-bis-O-beta-D-glucopyranosides of cyclopassifloic acids B and C, respectively. Also obtained in this investigation were the known compounds passiflorin (11) and passifloric acid (12).     

Resin glycosides from Ipomoea pes-caprae

Ipomoea pes-caprae (beach morning-glory; "ri?onina" for the herbal drug in Mexico) is prescribed by traditional healers to moderate "heat" in an infected kidney. The hexane-soluble extract from the aerial parts of this medicinal plant, through preparative-scale recycling HPLC, yielded six new lipophilic oligosaccharides of jalapinolic acid: pescaproside B (1) and pescapreins V-IX (2-6). The previously known pescaproside A (7), pescapreins I-IV (8-11), and stoloniferin III (12) were also identified in the analyzed material by means of HPLC comparison with authentic samples. The glycosidic acid structure for all pentasaccharides was confirmed as simonic acid B. Pescaproside B (1), an acylated glycosidic acid methyl ester, is structurally related to pescaprein III (10). Pescapreins V (2) and VI (3) are diasteroisomeric tetraglycosidic lactones of operculinic acid C. Both of these compounds contain (2S)-methylbutyric and n-dodecanoic acids as their esterifying residues. Pescapreins VII (4) and IX (6) are pentasaccharides that contain an n-decanoyl group as their esterifying fatty acid residue instead of the n-dodecanoyl found in pescapreins I (8) and IV (11). Pescaprein VIII (5) represents an isomer of pescaprein II (9) containing an n-dodecanoyl unit as the esterifying residue at position C-4 of the third rhamnose moiety and a 2-methylpropanoyl at C-2 of the second rhamnose. High-field NMR spectroscopy and FAB mass spectrometry were used to characterize all new isolated compounds.     

慈竹茹中木脂素类化学成分的研究

通过硅胶、大孔树脂、葡聚糖凝胶Sephadex LH-20和HPLC等多种色谱分离方法相结合,从慈竹茹Sinocalamusafinis茎的乙醇提取物的乙酸乙酯萃取部分中分离得到15个化合物;借助理化性质和波谱学数据分析,鉴定其结构为(+)-(1S,2R)-1,2-双(4-羟基-3-甲氧基苯基)-1,3-丙二醇(1),苏式-愈创木基甘油-β-O-4’-松柏基醚(2),赤式-愈创木基甘油-β-O-4’-松柏基醚(3),(+)-(7S,8R,8’R)-5’-甲氧基落叶松树脂醇(4),(+)-(7S,8R,8’R)-5,5’-二甲氧基落叶松树脂醇(5),(±)-秃毛冬青素Ⅰ(6),(-)-丁香树脂酚(7),(-)-杜仲树脂酚(8),(-)-(8R,8R’)-4,4’-二羟基-3,3’,5,5’-四甲氧基木脂烷-9,9’-二醇(9),(-)-开环异落叶松树脂酚-9,9’-缩丙酮(10),(+)-珍珠花树环木脂醇(11),2,6-二甲氧基吡喃-4-酮(12),β-谷甾醇(13),4-羟基桂皮酸(14)和2,6-二甲氧基对苯醌(15)。这些化合物均为首次从慈竹属植物中分离得到,其中化合物12为新天然产物。     

Synthesis of (7S,15S)- and (7R,15S)-dolatrienoic acid

The stereospecific synthesis of (7S,15S)- and (7R,15S)-dolatrienoic acids (2) was achieved using an approach consisting of 16 linear steps. The C-11--C-16 unit was prepared in seven steps from ethyl (S)-lactate and coupled using a trans-selective Wittig--Schlosser reaction to the C-7--C-10 fragment. Chirality at the C-7 position was introduced using an Evan's-type chiral auxiliary in a cobalt-mediated Reformatsky reaction to give the (3S,11S)-aldehyde 24. Subsequent Wittig reaction with a phosphonium salt derived in three steps from tiglic acid gave (7S,15S)-dolatrienoic acid, one of the four possible diastereoisomers of the nonpeptide portion of the strong cancer cell growth inhibitory cyclodepsipeptide dolastatin 14 (1). A second diastereoisomer, (7R,15S)-dolatrienoic acid, was synthesized employing chiral oxazolidinone 21 by an analogous synthetic route.     

Cembranolides from the leaves of Croton gratissimus

Ten new cembranolides, (-)-(1R*,4R*,10R*)-4-methoxycembra-2E,7E,11Z-trien-20,10-olide (1), (-)-(1S*,4R*,10R*)-1-hydroxy-4-methoxycembra-2E,7E,11Z-trien-20,10-olide (2), (-)-(1S*,4S*,10R*)-1,4-dihydroxycembra-2E,7E,11Z-trien-20,10-olide (3), (-)-(1S*,4S*,10R*)-1,4-dihydroxycembra-2E,7E,11Z-trien-20,10-olide (4), (+)-(10R*)-cembra-1E,3E,7E,11Z,16-pentaen-20,10-olide (5), (+)-(10R*)-cembra-1Z,3Z,7E,11Z,15-pentaen-20,10-olide (6), (+)-(5R*,10R*)-5-methoxycembra-1E,3E,7E,11Z,15-pentaen-20,10-olide (7), (+)-(1S*,4S*,7R*,10R*)-1,4,7-trihydroxycembra-2E,8(19),11Z-trien-20,10-olide (8), (-)-(1S*,4S*,7S*,10R*)-1,4,7-trihydroxycembra-2E,8(19),11Z-trien-20,10-olide (9), and (+)-(1S*,4R*,8S*,10R*)-1,4,8-trihydroxycembra-2E,6E,11Z-trien-20,10-olide (10), together with six known compounds, lupeol, 4(15)-eudesmene-1β,6α-diol, α-glutinol, 24-ethylcholesta-4,22-dien-3-one, (+)-(1R*,10R*)-cembra-2E,4E,7E,11Z-tetraen-20,10-olide, and (+)-(1R*,4S*,10R*)-4-hydroxycembra-2E,7E,11Z-trien-20,10-olide (4a), have been isolated from the leaves of Croton gratissimus. The acetyl derivatives of 8 and 4a were evaluated against a chloroquine-sensitive strain of Plasmodium falciparum (D10).     

Acylated glycosides of hydroxy fatty acid methyl esters generated from the crude resin glycoside (pharbitin) of seeds of Pharbitis nil by treatment with indium(III) chloride in methanol

Treatment of the crude ether-insoluble resin glycoside (convolvulin) from seeds of Pharbitis nil (Pharbitis Semen), called pharbitin, with indium(III) chloride in methanol provided seven oligoglycosides of hydroxy fatty acid methyl esters partially acylated by 2-methyl-3-hydroxybutyric (nilic) and 2S-methylbutyric acids. Their structures were elucidated on the basis of NMR and MS data and chemical conversions.     

Oleanane and taraxerane glycosides from the roots of Gomphrena macrocephala

Phytochemical screening of the roots of Gomphrena macrocephala, with particular attention to its triterpene glycoside constituents, has resulted in the isolation of two new oleanane glycosides (1 and 2) and a new taraxerane glycoside (3). The structures of 1-3 were determined as 11alpha,12alpha-epoxy-3beta-[(O-beta-D-glucuronopyranosyl)oxy]olean-28,13-olide (1), 11alpha,12alpha-epoxy-3beta-[(O-beta-D-galactopyranosyl-(1-->3)-O-[beta-D-glucopyranosyl-(1-->2)]-beta-D-glucuronopyranosyl)-oxy]olean-28,13-olide (2), and 11alpha,12alpha-epoxy-3beta-[(O-beta-D-glucuronopyranosyl)oxy]taraxer-14-en-28-oic acid beta-D-glucopyranosyl ester (3), respectively, on the basis of their spectroscopic data and the results of hydrolysis. The aglycones (1a and 3a) of 1-3 with an epoxy group showed cytotoxic activity against HSC-2 human oral squamous carcinoma cells.     

Secondary metabolites from the roots of Astragalus trojanus

Six novel cycloartane-type glycosides were isolated from the roots of Astragalus trojanus. Two of these, compounds 1 and 2, have (20R, 24S)-epoxy-3beta,6alpha,16beta,25-tetrahydroxycycloartane as the aglycon, while compounds 3-6 possess 3beta,6alpha,16beta,(24S), 25-pentahydroxycycloartane as the aglycon. The saccharide moieties linked to the C-3, C-6, and C-24 or C-25 positions of the aglycons in 1-6 contained either xylopyranose, glucopyranose, rhamnopyranose, or arabinopyranose units. Structure elucidation of compounds 1-6 was accomplished through the extensive use of 1D and 2D NMR techniques. In addition, a new oleanene glycoside (7) and a new tryptophan derivative (8) were also isolated and characterized.     

Tyrianthinic acids from Ipomoea tyrianthina and their antimycobacterial activity, cytotoxicity, and effects on the central nervous system

Four new partially acylated tetrasaccharides of 11-hydroxyhexadecanoic acid (1-4) were isolated from a methanolic extract of Ipomoea tyrianthina. The structures of these compounds were elucidated by spectroscopic and chemical methods. The resin glycoside composition of I. tyrianthina varied with the location of growth in Mexico. Compounds 1-4 showed antimycobacterial activity, were cytotoxic against the KB cell line, and, in a mouse model, exhibited potentiation of hypnosis induced by pentobarbital, protected against seizures induced by pentylenetetrazole, and released GABA and glutamic acid.     

Neamphamide A, a new HIV-inhibitory depsipeptide from the Papua New Guinea marine sponge Neamphius huxleyi

A new HIV-inhibitory cyclic depsipeptide, neamphamide A (2), was isolated from a Papua New Guinea collection of the marine sponge Neamphius huxleyi. Its structure was established through interpretation of spectroscopic data and by acid hydrolysis, derivatization of the free amino acids, and LC-MS analysis of the derivatives. Neamphamide A (2) contains 11 amino acid residues and an amide-linked 3-hydroxy-2,4,6-trimethylheptanoic acid moiety. The amino acid constituents were identified as L-Leu, L-NMeGln, D-Arg, D- and L-Asn, two residues of D-allo-Thr, L-homoproline, (3S,4R)-3,4-dimethyl-L-glutamine, beta-methoxytyrosine, and 4-amino-7-guanidino-2,3-dihydroxyheptanoic acid. In a cell-based XTT assay, 2 exhibited potent cytoprotective activity against HIV-1 infection with an EC50 of approximately 28 nM.     

Phrygiasterol, a cytotoxic cyclopropane-containing polyhydroxysteroid, and related compounds from the pacific starfish Hippasteria phrygiana

The new cyclopropane-containing steroid phrygiasterol (1) and steroid glycoside phrygioside B (2), along with previously known borealoside C (2a) and (20R,24S)-5alpha-cholesta-3beta,6alpha,8,15alpha,24-pentaol (3), have been isolated from the Pacific starfish Hippasteria phrygiana. On the basis of spectroscopic analyses, using 1D and 2D NMR techniques and some chemical transformations, the structures of 1 and 2 have been established as (20R,24R,25R)-24,26-cyclo-5alpha-cholesta-3beta,6alpha,8,15alpha,16beta,27-hexaol (1) and the sodium salt of (20R,24S)-24-O-(3-O-methyl-4-O-sulfate-beta-d-xylopyranosyl)-5alpha-cholesta-3beta,6alpha,8,15alpha,24-pentaol (2), respectively. Compound 1 inhibited the growth of Ehrlich carcinoma cells with an IC(50) of 50 microg/mL, whereas 2 induced apoptosis of the same cells (EC(50)=70 microg/mL) and inhibited Ca(2+) influx into mouse spleenocytes (EC(50)=20microg/mL).     

Batatins I and II, ester-type dimers of acylated pentasaccharides from the resin glycosides of sweet potato

Batatins I (1) and II (2), two ester-type dimers of acylated pentasaccharides, have been isolated by recycling HPLC from the hexane-soluble extract of sweet potato (Ipomoea batatas var. batatas). The structures were elucidated by a combination of high-resolution NMR spectroscopy and mass spectrometry. Complete analysis and unambiguous assignments of the 1H and 13C NMR spectra of 1 and 2 were achieved by 2D shift correlation measurements. The glycosidic acid forming each branched pentasaccharide monomeric unit was confirmed as simonic acid B. Three different fatty acids esterify this core at the same positions in both batatins: C-2 on the second rhamnose unit and C-4 and C-2 (or C-3) on the third rhamnose moiety. The acylating residues were identified as (+)-(2S)-methylbutanoic, dodecanoic (lauric), and cinnamic acids. The site of lactonization by the aglycon in unit A was placed at C-3 of the second saccharide. The position for the ester linkage for monomeric unit B on the macrocylic unit A was identified as C-3 of the terminal rhamnose' '. Through spectroscopic simulation of these complex oligosaccharides, the chemical shifts and coupling constants were deduced for the overlapped proton resonances with a non-first-order resolution. The experimental NMR spectroscopic values registered for batatinoside I (3), a new polyacylated macroyclic pentasaccharide also isolated from this plant, were used as the starting point for spectral simulation of 1 and 2. Both polymers 1 and 2 represent dimers of compound 3.     

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.