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Ten new polyhydroxysteroidal glycosides, anthenosides L-U (1-10), with rare positions of carbohydrate fragment attachments, were isolated from the starfish Anthenea aspera. The structures of 1-10 were established by NMR and ESIMS techniques as well as by chemical transformations. The unoxidized Δ 22 -24-nor-cholestane (1), (24S)-Δ 22 -24-methylcholestane (2-5), and Δ 22 -cholestane (7) side chains of the steroidal aglycons, 3-O-methyl-β-d-galactofuranosyl residue (2, 8), and 5α-cholest-8(14)-ene-3α,7β,16α-trihydroxysteroidal nucleus (9, 10) have not been found previously in starfish polar steroidal compounds. The mixture of glycosides 9 and 10 showed hemolytic activity with an EC 50 = 8 μM. Compound 4 at a dose of 10 μM exhibited a potential immunomodulatory action, decreasing by 24% the intracellular ROS content in RAW 264.7 murine macrophages, induced by pro-inflammatory endotoxic lipopolysaccharide from E. coli.

Five new steroid glycosides, luzonicosides B-E (2-5), belonging to a rare structure group of marine glycosides, containing carbohydrate moieties incorporated into a macrocycle, and a related open carbohydrate chain steroid glycoside, luzonicoside F (6), were isolated from the starfish Echinaster luzonicus along with the previously known cyclic steroid glycoside luzonicoside A (1). The structures of compounds 2-6 were established by extensive NMR and ESIMS techniques as well as chemical transformations. Luzonicoside A (1) at concentrations of 0.01-0.1 μM was shown to be potent in lysosomal activity stimulation, intracellular ROS level elevation, and NO synthesis up-regulation in RAW 264.7 murine macrophages. Luzonicoside D (4) was less active in these biotests.

The dried roots of Cynanchum stauntonii in having cough-relieving efficacy are commonly included in traditional antitussive formulas. The active components in a C. stauntonii root extract responsible for airway relaxation were isolated using an ex vivo bioassay-guided fractionation method, in which subfractions were evaluated for their inhibitory effects on the contraction of isolated rat tracheal rings by isometric tension measurements. A steroidal glycoside, cynatratoside B (1), identified by LC-MS and NMR spectroscopic analysis, was shown to have potent inhibition on acetylcholine- and carbachol-induced tracheal contractions. The present data provide scientific evidence to support the traditional use of C. stauntonii as an antitussive herbal medicine.

Three new 19-hydroxy steroidal glycosides, namely, junceellosides E-G (2-4), were isolated together with the known analogue junceelloside C (1) from the South China Sea gorgonian Dichotella gemmacea. The structures of these compounds were elucidated by a combination of detailed spectroscopic analyses, chemical methods, and comparison with reported data. These glycosides are found to have sugar moieties of both β-l- and β-d-arabinopyranoses by HPLC analysis of their thiocarbamoyl-thiazolidine derivatives and those of authentic d- and l-arabinoses, leading to the structure revision of junceelloside C (1). This is the first report of steroidal glycosides from the gorgonian D. gemmacea and the first report of glycosides with β-l-arabinopyranose from marine sources.

Four new steroidal glycosides, acanthifoliosides G-J (1-4), were isolated as minor constituents from the Caribbean marine sponge Pandaros acanthifolium. These metabolites are characterized by a highly oxygenated D ring and the presence of a disaccharide rhamnose-glucose residue and a rhamnose at positions C-3 and C-15, respectively. Their structures were established on the basis of extensive interpretation of 1D and 2D NMR data and HRESIMS analyses. The absolute configurations of the glucose and rhamnose sugars were determined by preparing aldose o-tolylthiocarbamate derivatives and comparison to authentic standards by LC/HRESIMS. Acanthifolioside G (1) exhibited antioxidant and cytoprotective activities.

Five new steroidal glycosides (1-5) and nine known compounds were isolated from Solanum violaceum. Indiosides G (1) and H (2) are spirostene saponins with an iso-type F ring, indioside I (3) is a spirostane saponin, and indiosides J (4) and K (5) are unusual furostanol saponins with a deformed F ring. These structures represent rare naturally occurring steroidal skeletons. The structures of the new compounds were elucidated using 1D and 2D spectroscopic techniques and acid hydrolysis. Compounds 2, 3, and 7-9 exhibited cytotoxic activity against six human cancer cell lines (HepG2, Hep3B, A549, Ca9-22, MDA-MB-231, and MCF-7) with IC(50) values of 1.83-8.04 μg/mL. Steroidal saponins 3, 8, and 9 showed inhibitory effects on superoxide anion generation with IC(50) values of 2.84 ± 0.18, 0.62 ± 0.03, and 1.62 ± 0.59 μg/mL, respectively. Saponins 8 and 9 also inhibited elastase release with IC(50) values of 111.05 ± 7.37 and 4.04 ± 0.51 μg/mL, respectively. Structure-activity relationship correlations of these compounds with respect to cytotoxic and anti-inflammatory effects are discussed., (© 2012 American Chemical Society and American Society of Pharmacognosy)

Ten new polyhydroxysteroidal glycosides, anthenosides B-K (2-11), were isolated from the ethanol extract of the starfish Anthenea chinensis. Their structures were elucidated by extensive spectroscopic studies and chemical evidence. The unprecedented carbohydrate chain 6-O-methyl-beta-d-galactofuranosyl-(1-->3)-(6-O-methyl-beta-d-galactofuranose) was present in all the compounds except compounds 10 and 11. Compounds 5, 7, a mixture of 8 and 9, and a mixture of 10 and 11 showed inhibitory activity against human tumor K-562 and BEL-7402 cells. Furthermore, the mixture of 10 and 11 also exhibited cytotoxicity against human tumor U87MG cells and promoted tubulin polymerization.

Four new steroidal sapogenins (1-4), named diosbulbisins A-D, two new spirostane glycosides, diosbulbisides A (5) and B (6), one new cholestane glycoside, diosbulbiside C (7), and the known compounds 8-10 were isolated from rhizomes of Dioscorea bulbifera. Their structures were elucidated by 1D and 2D NMR techniques, HRFTMS, and chemical methods. The unusual furospirostanol sapogenin skeletons, as found in compounds 3 and 4, are reported in the family Dioscoreaceae for the first time. Cytotoxicity of compounds 1-10 was evaluated using two human hepatocellular carcinoma cell lines (Bel-7402 and SMMC7721).

The MS fragmentation behavior of the C-21 steroidal glycosides from Dregea sinensis var. corrugata was investigated by positive and negative ion electrospray ionization MS using a multistage tandem mass spectrometer equipped with an ion trap analyzer. The mass fragmentation patterns of steroidal glycosides substituted with an orthoacetate group were summarized, and the fragmentation patterns were applied to the online structure identification of the steroidal glycosides in the extract. Eighteen new C-21 steroidal glycosides were identified by means of HPLC-HRESIMS and HPLC-DAD-ESIMS(n). Three new compounds (1, 4, and 7) were identified by HPLC-DAD-ESIMS(n), and their structures were elucidated by use of 1D and 2D NMR methods. The structures identified by MS are fully consistent with those elucidated by NMR data. The present study shows that HPLC-DAD-ESIMS(n) can be used as an effective tool to rapidly identify compounds and guide the isolation of target compounds from crude plant extracts.

Three novel steroidal triglycosides, designated as kurilensosides A, B, and C (1- 3), were isolated along with a new steroidal diglycoside, kurilensoside D (4), and two new (6, 7) and one known (5) polyhydroxysteroid from the alcoholic extract of the Far Eastern starfish Hippasteria kurilensis. Compounds 1-3 are the first triglycosides containing two carbohydrate chains found from starfish. The structures of 1-7 were elucidated by spectroscopic methods (mainly 2D NMR) and chemical derivatization. Glycosides 1-4 and steroids 6 and 7 inhibited sea urchin egg fertilization by sperm preincubated with these compounds.

In the course of our studies on antidiabetogenic compounds from natural medicines and medicinal foodstuffs, a methanolic extract of the fruits of Solanum lycocarpum showed an inhibitory effect on the increase of serum glucose levels in oral sucrose-loaded rats. Through bioassay-guided separation, three known steroidal alkaloid oligoglycosides, solamargine (1), solasonine (3), and 12-hydroxysolasonine (5), were isolated from the active fraction together with two new steroidal alkaloid oligoglycosides, robeneosides A (2) and B (4). The major constituents, solamargine (1) and solasonine (3), exhibited an inhibitory effect on the increase of serum glucose levels in oral sucrose-loaded rats. In addition, these compounds suppressed gastric emptying in mice. However, this methanolic extract from S. lycocarpum fruits did not have any effect on intestinal alpha-glucosidase (sucrase and maltase) in vitro. It was concluded that these steroidal alkaloid oligoglycosides, 1 and 3, inhibited the increase of rat serum glucose levels by suppressing the transfer of sucrose from the stomach to the small intestine.

Two new sulfated polyhydroxylated steroidal xylosides, minutosides A (1) and B (2), together with the known pycnopodioside B (3), have been isolated from the brine shrimp active fraction of the ethanolic extract of the starfish Anasterias minuta. The structures have been elucidated by extensive 1D and 2D NMR as well as FABMS analysis and chemical methods. Compound 2 is the first example of a polyhydroxylated steroidal xyloside containing an amide function in the aglycon side chain. The three xylosides exhibited antifungal activity against Cladosporium cucumerinum and Aspergillus flavus.

Phytochemical analyses have been carried out on the fresh bulbs of Ornithogalum thyrsoides with particular attention to the steroidal glycoside constituents, resulting in the isolation of four new spirostanol saponins and seven new cholestane glycosides, together with three known steroidal compounds. The structures of the new glycosides were determined on the basis of their spectroscopic data, including 2D NMR spectroscopy, and the results of hydrolytic cleavage. The isolated compounds were evaluated for their cytotoxic activities against HL-60 human promyelocytic leukemia cells and HSC-2 human oral squamous cell carcinoma cells.

Three new steroidal alkaloid glycosides, lycoperosides F-H (1-3), were isolated from tomato fruits (Lycopersicon sculentum) along with lycoperosides A-D, esculeoside A, and rutin. The structures of these glycosides were characterized as the 3-O-beta-lycotetraosides of 23(R)-23-acetoxy-27-hydroxy-27-O-beta-d-glucopyranosyltomatidine (1), (23S,24R)-23-acetoxy-24-O-beta-d-glucopyranosylsoladulcidine-24-ol (2), and 22-isopimpifolidine (3), by means of their spectroscopic data. Also obtained was the new natural product lycoperodine-1 (4).

Two new C-21 steroidal glycoside epimers, paniculatumosides A and B (1 and 2), based on a 13,14:14,15-disecopregnane-type skeleton, with neocynapanogenin B (3) and neocynapanogenin C (4) as two new aglycons, were isolated from the roots of Cynanchum paniculatum. Their structures were determined by spectral data interpretation.

New steroidal oligoglycosides mycalosides B-I (2-9) have been isolated from the polar extract of the Caribbean sponge Mycale laxissima, and their structures have been elucidated by 1D and 2D NMR ((1)H, (13)C, DEPT, COSY-45, COSY-RCT, HSQC, HMBC, and NOESY spectra) and MALDI-TOF mass spectrometry. Mycalosides B (2) and C (3) were shown to be 27- and 28-nor derivatives of the previously known tetraoside mycaloside A (1). Mycaloside D (4) differs from 1 only in the presence of an additional acetyl group in the carbohydrate moiety. Mycaloside E (5) was structurally identified as a 28-nor-4-dehydroxy derivative of 1. Mycalosides F-H (6-8), differing from each other by the structures of their side chains and nonacetylated (7, 8) or acetylated (6) tetrasaccharide carbohydrate moieties, have new 5(6)-unsaturated 3 beta,4 beta,21-trihydroxy-15-keto-steroidal aglycons. Mycaloside I (9) is a tetraoside of a new 7,24(28)-diunsaturated 3beta,15 beta,29-trihydroxystigmastane aglycon. It was established that the total fraction of the mycalosides as well as mycalosides A (1) and G (7) inhibit the fertilization of eggs by sperm of the sea urchin Strongylocentrotus nudus preincubated with these compounds.

Four new 5alpha-steroidal glycosides with an unusual framework, funingenosides A (1), B (2), C (3), and D (4), were isolated from the roots of Parepigynum funingense. Their structures were elucidated on the basis of 1D and 2D NMR techniques. The structure and relative stereochemistry of compound 1 were demonstrated by X-ray crystallographic analysis.

Further phytochemical analysis aimed at the steroidal glycoside constituents of the leaves of Cestrum nocturnum has resulted in the isolation of eight new steroidal glycosides (1-8), which were classified into a spirostanol saponin (1), a furostanol saponin (2), a pseudo-furostanol saponin (3), two pregnane glycosides (4, 5), two cholestane glycosides (6, 7), and pregnane-carboxylic acid gamma-lactone glycoside (8), and of two known spirostanol glycosides (9, 10). The structures of the new compounds were elucidated on the basis of chemical and spectroscopic evidence.

Four new steroidal saponins, anguiviosides III (1), XI (2), XV (3), and XVI (4), were isolated and characterized from the fruits of Solanum anguivi. Their structures were elucidated on the basis of spectroscopic analysis. The occurrence of the cholestane glycosides 3 and 4 is considered from a biogenetic point of view.

Two novel steroidal 24-O-xylosides, designated as rathbuniosides R(1) (1) and R(2) (2), and the known amurensoside A (3) and 3-O-sulfomarthasterone (4) have been isolated from the starfish Asterias rathbuni. The structures of all the compounds were determined from their spectroscopic data, including one- and two-dimensional NMR methods. The compounds 1 and 4 inhibit the cell division of fertilized sea urchin eggs at doses of 7.0 x 10(-5) and 2.9 x 10(-5) M, respectively.

A chemical investigation of the aerial parts of Polianthes tuberosa resulted in the isolation of a new bisdesmosidic cholestane glycoside (1) and three new spirostanol saponins (2-4), along with a known cholestane glycoside. The structures of new glycosides were determined by spectroscopic analysis, including 2D NMR spectroscopic data, and the results of hydrolytic cleavage. The isolated compounds were evaluated for their cytotoxic activity on HL-60 human promyelocytic leukemia cells.

Thirteen new (1-13) and seven known (14-20) steroid glycosides were isolated from Henricia downeyae, collected from the offshore waters of the northern Gulf of Mexico. Ethanolic extracts of these starfish caused growth inhibition in bacteria and fungi, potent antifouling activity against barnacle and bryozoan larvae, and feeding deterrent activity against a marine fish. The known compounds are typical glycosides found in several species of the family Echinasteridae, i.e., Echinaster sp. and Henricia laeviuscola. One of the new compounds belongs to this group, whereas the remaining 12 new compounds represent a novel series of steroid glycosides which have aglycons with structural similarities to the "asterosaponins". They possess a delta 9(11) 3 beta, 6 alpha-dihydroxysteroidal aglycon with 23-oxo or 22,23-epoxy functionalities and often a 20-hydroxyl group in the side chain. The sulfate is located at C-6 and the saccharide moiety at C-3, in contrast with the asterosaponins which have the sulfate at C-3 and the oligosaccaride moiety at C-6. All the new compounds contain a glucuronic acid unit, which is uncommon among steroid glycosides from echinoderms. The structures of the new compounds, isolated in amounts ranging from 3.4 to 0.9 mg, were determined by interpretation of their spectral data and by comparison with spectral data of known compounds.

This paper describes a complete analysis of the glycoside and polyhydroxysteroid constituents of the starfish Nardoa tuberculata, collected at Zampa, Okinawa, Japan. Besides a group of known non-sulfated steroidal diglycosides, halitylosides A [5], B [6], D [7], E [8], and F [9], and two known polyhydroxysteroids 10 and 11, N. tuberculata also contains four new sulfated steroidal glycosides 1-4 closely related to the previous halitylosides. The antifungal activities and the effects on the development of fertilized sea urchin eggs of some steroid components from this starfish were examined.

Nine new cytotoxic steroidal glycosides 1-9 have been isolated from the starfish Fromia monilis collected off New Caledonia. Structures of these compounds, which include four mono-(1-4), two di-(5,6), and three glycosides (7-9), were elucidated through spectral interpretation. Monilosides G [7], H [8], and I [9] are the first tri-glycosides to be found among the group of glycosides of polyhydroxilated steroids from starfishes.

In continuation of work on Solanum incanum a new steroidal alkaloid glycoside has been isolated from the fresh berries, which is named incanumine, and characterized as O(3)-[beta-D-xylopyranosyl-(1----3glu)-[beta-D-xylopyranosyl-(1--- -4rha)- alpha-L-rhamnopyranosyl-(1----4)]-beta-D-glucopyranosyl)-solasodine++ +. Solamargine, solasodine, ursolic acid, and ursolic acid derivatives (3-O-palmitoyl ursolic acid, 3-O-crotonyl ursolic acid, 3-O-propionyl ursolic acid) exhibited significant cytotoxic effects against human PLC/PRF/5 cells in vitro. Esterification of ursolic acid with aliphatic acids clearly enhanced the cytotoxic effects against human PLC/PRF/5 cells in vitro.