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Neolignans from the Parasitic Plants. Part 1. Aeginetia Indica
Abstract
Two new neolignans, namely balanophonin 4‐O‐β‐d‐glucopyranoside and aegineoside together with four known neolignans have been isolated from the whole plant of Aeginetia indica Linn. (Orobanchaceae). Their structures were established by spectroscopic and chemical methods.
... The seven known lignans were identified as (+)-pin- 26) armaoside (6), 27) 28) scorzonoside (8), 29) and balanophonin 4-O-β-Dglucopyranoside (9) 30) based on their spectroscopic data compared with the reported data in the literature. ...
In our quest for structurally intriguing compounds from Korean medicinal plant sources, chromatographic separation of the 80% MeOH extract from Firmiana simplex resulted in the isolation and identification of three new lignan glycosides (1–3), together with six known lignan glycosides (4–9). The structures of 1–3 were determined on the basis of spectroscopic analyses, including extensive 2D-NMR and enzyme hydrolysis. Nitric oxide (NO) production was evaluated in the lipopolysaccharide-activated microglial cell line, BV-2 to investigate the anti-neuroinflammatory effects of the isolated compounds (1–9). Compound 7 marginally inhibited NO levels with IC50 values of 59.83 µM.
Graphical Abstract Fullsize Image
... , 56.9 (OCH 3 ). The above data were identical to the literature data [22]. ...
An activity-directed fractionation and purification process was used to isolate antioxidant components from cassava stems produced in Hainan. The ethyl acetate and n-butanol fractions showed greater DPPH˙and ABTS·+ scavenging activities than other fractions. The ethyl acetate fraction was subjected to column chromatography, to yield ten phenolic compounds: Coniferaldehyde (1), isovanillin (2), 6-deoxyjacareubin (3), scopoletin (4), syringaldehyde (5), pinoresinol (6), p-coumaric acid (7), ficusol (8), balanophonin (9) and ethamivan (10), which possess significant antioxidant activities. The relative order of DPPH· scavenging capacity for these compounds was ascorbic acid (reference) > 6 > 1 > 8 > 10 > 9 > 3 > 4 > 7 > 5 > 2, and that of ABTS·+ scavenging capacity was 5 > 7 > 1 > 10 > 4 > 6 > 8 > 2 > Trolox (reference compound) > 3 > 9. The results showed that these phenolic compounds contributed to the antioxidant activity of cassava.
This study investigates Symplocos cochinchinensis (Lour.) S. Moore leaves and stems, commonly known as Symplocos, a plant indigenous to Asia renowned for its traditional use in holistic medicine. A comprehensive phytochemical analysis of S. cochinchinensis led to the isolation of two new lignans, namely symplolignans A and B (1 and 2) along with eleven known lignan glucosides: nortrachelogenin 4‐O‐β‐D‐glucopyranoside (3), nortracheloside (4), matairesinol 4‐O‐β‐D‐glucopyranoside (5), lariciresinol 4′‐O‐β‐D‐glucopyranoside (6), balanophonin 4‐O‐β‐D‐glucopyranoside (7), dehydrodiconiferyl alcohol 4‐O‐β‐D‐glucopyranoside (8), dehydrodiconiferyl alcohol γ'‐O‐β‐D‐glucopyranoside (9), 3‐(β‐D‐glucopyranosyloxymethyl)‐2‐(4‐hydroxy‐3‐methoxyphenyl)‐5‐(3‐hydroxypropyl)‐7‐methoxy‐(2R,3S)‐dihydrobenzofura (10), and pinoresinol 4′‐O‐β‐D‐glucopyranoside (11). Their chemical structures were elucidated using 1D‐ and 2D‐NMR, mass spectrometry, and their spectroscopic data were compared with those reported in literatures. Furthermore, all compounds were evaluated for their hepatoprotective effects using the Resazurin reduction assay in HepG2 hepatocellular carcinoma cells. Compounds 1, 5, 7, and 8 exhibited notable hepatoprotective efficacy, with cell viability ranging from 105.0 ± 2.6 to 109.2 ± 3.3 at a concentration of 10 µM. This research highlights the therapeutic potential of these compounds and enhanced to the understanding of lignans and neolignans in liver cell proliferation.
A phytochemical investigation of the methanolic extract of aerial parts of the Acanthus ilicifolius led to the isolation of two new lignan glycosides, acaniliciosides A and B (1 and 2), together with ten known compounds (3-12). The structures of isolated compounds were elucidated based on HR-ESI-MS, 1D and 2D NMR spectroscopic data. The absolute configurations of two new compounds were established by CD spectra. With the exception of compound 12, other compounds inhibited NO production in LPS activated RAW264.7 cells with IC50 values of 2.14-28.18 µM, as potent as that of the positive control of NG-monomethyl-L-arginine acetate (L-NMMA, IC50 of 32.50 µM). In addition, compounds 5-8 showed cytotoxic effects against SK-LU-1 and HepG2 cell lines with the IC50 values ranging from 16.48 to 76.40 μM compared to the positive control (ellipticine) with the IC50 values ranging from 1.23 to 1.46 μM.
A new iridoid glycoside, 6-O-[(2E,6R)-8-hydroxy-2,6-dimethyl- 2-octenoyl]-catalpol (kanchanikoside, 1) was isolated from the leaves and twigs of Santisukia pagetii. In addition to the new compound, the 17 known glycosides were isolated: nemoroside, 6"(Z)-nemoroside, ambiguuside, specioside, verminoside,6-trans-feruloylcatalpol, 6,6'-di-O-caffeoylcatalpol,amphicoside, 6-O-veratroylcatalpol,citrusinB,(7R,8S)-balanophonin4-O--D-gluco-pyranoside,(7R,8S)-dehydrodiconiferyl-O--D-glucopyranoside,martynoside, benzylO--D-xylopyranosyl-(1→6)--D-glucopyranoside,benzylO--D-apio-furanosyl-(1→6)--D-glucopyranoside,icarisideD 1 and(6S,9R)-roseoside.Their structuresweredeterminedbasedonthespectroscopicevidenceincluding1Dand 2DNMR,andHR-ESI-TOF-MSexperiments.
A callus culture of Lactuca aculeata, except for commonly distributed caffeic acid derivatives typically found in the Asteraceae family (chlorogenic acid, methyl caffeate, 1,5- dicaffeoylquinic acid), yielded bioactive lignans: (+)-5-methoxybalanophonin, syringaresinol, (+)-balanophonin-9-O-β-glucopyranoside, (+) buddlenol A, (−)-dihydrodehydrodiconiferyl alcohol-4-O-β-glucopyranoside and (−)-dihydrodehydrodiconiferyl alcohol-9-O-β-glucopyranoside. Sesquiterpene lactones characteristic of the parent plant were not found in the examined tissue. This is the first report on the presence of bioactive neolignans: 5-methoxybalanophonin, balanophonin glucoside and buddlenol A in the genus Lactuca L.
A new highly oxygenated acyclic sesquiterpenoid (2E, 6E)-8,10,11-trihydroxyl-7,11-dimethyl-3-hydroxymethyl-2,6-dodecadienoic acid (1) and its glucoside (2), together with a new pinane monoterpene disaccharide glucoside 6,6-dimethyl-2-methlenebicyclo [3.1.1]hept-3-O-(6-O-apiofuranosyl)-β-d-glucopyranoside (3) were isolated from hydrophilic extract of Dichondra repens. Their structures were elucidated on the basis of spectroscopic analyses and chemical methods. The three compounds did not show any cytotoxic activity (IC50 > 20 μM) against two human lung cancer cell lines (NCI-H661 and A549).
Objective: To study the chemical constituents of Acanthopanax senticosus from Changbai Mountain area and their free radical scavenging activities. Methods: The chromatography on silica gel column, ODS column, and semi-preparative HPLC were used to isolate and purify the constituents and their structures were identified on the basis of spectral data analyses. Also the free radical scavenging activities of the compounds were evaluated. Results: Eleven compounds were obtained from A. senticosus and were identified as bis (2-ethylhexyl) phthalate (1), diisobutyl phthalate (2), lariciresinol (3), tripterygiol (4), 8, 8'-bisdihydrosiringenin (5), isofraxidin (6), syringaresinol (7), balanophonin (8), 3, 3'-dimethoxy-4, 8'-oxyneoligna-9, 4', 7', 9'-tetraol (9), 1-(4'-hydroxy-3'- methoxyphenyl)-2-[4″-(3-hydroxypropyl)-2″, 6″-dimethoxyphenoxy] propane-1, 3-diol (10), and sesamin (11). Conclusion: Compounds 1-5 and 8-11 are obtained from A. senticosus for the first time. Compounds 3, 4, 6, and 7 show the remarkable scavenging activities toward DPPH free radical with IC 50 values of 0.01, 0.01, 0.01, and 0.66 μg/mL, respectively, which could provide the reference for the development of leading compounds in anti-oxidant and anti-aging aspects of the drugs.
One new neolignan identified as 2, 3-( trans) -dihydro-2-(4-hydroxy-3-methoxyphenyl) -3-[(beta-D-glucopyranosyloxy) methyl]-7-methoxybenzofuran-5-propenoic acid (1) and five known steroidal glycosides namely torvoside A(2), torvoside C(3), torvoside H(4), solanolactoside A (5), (25S)-6alpha-hydroxy-5alpha-spirostan-3-one-6-0-[alpha-L-rhamnopyranosyl-(1-->3-beta3)-beta-D-D-quinovopyr-anoside] (6) were isolated from the fruits of Solanum torvum. Their structures were elucidated on the basis of 1D, 2D NMR and MS spectroscopic analysis.
Two new phenylpropanoid glycosides, α-L-rhamnopyranosyl-(1→3)-1-O-caffeoyl-β-D-glucopyrano-side and 2″,3″′-diacetyl acteoside, together with seven known compounds have been isolated from the parasitic plant, Aeginetia indica Linn. Their structures were established by spectroscopic and chemical methods.
Plant metabolomics is increasingly used for pathway discovery and to elucidate gene function. However, the main bottleneck is the identification of the detected compounds. This is more pronounced for secondary metabolites as many of their pathways are still underexplored. Here, an algorithm is presented in which liquid chromatography-mass spectrometry profiles are searched for pairs of peaks that have mass and retention time differences corresponding with those of substrates and products from well-known enzymatic reactions. Concatenating the latter peak pairs, called candidate substrate-product pairs (CSPP), into a network displays tentative (bio)synthetic routes. Starting from known peaks, propagating the network along these routes allows the characterization of adjacent peaks leading to their structure prediction. As a proof-of-principle, this high-throughput cheminformatics procedure was applied to the Arabidopsis thaliana leaf metabolome where it allowed the characterization of the structures of 60% of the profiled compounds. Moreover, based on searches in the Chemical Abstract Service database, the algorithm led to the characterization of 61 compounds that had never been described in plants before. The CSPP-based annotation was confirmed by independent MS(n) experiments. In addition to being high throughput, this method allows the annotation of low-abundance compounds that are otherwise not amenable to isolation and purification. This method will greatly advance the value of metabolomics in systems biology.
Three new acylated flavonoid C-glycosides, 6‴-(-)-phaseoylspinosin (1), 6‴-(3″″,4″″,5″″-trimethoxyl)-(E)-cinnamoylspinosin (2), and 6‴-(4″″-O-β-D-gluco-pyranosyl)-benzoylspinosin (3), were isolated from the seeds of Ziziphus mauritiana (Rhamnaceae). A further 19 known compounds including eight spinosin analogues (4–11) were also isolated. Their structures were elucidated by means of spectroscopic analysis and chemical method. Among spinosin derivatives 1, 2, 4, 7, 8, and triterpenoid saponin 14, jujuboside A (14) displayed moderate acetylcholinesterase (AchE) inhibitory activity with an inhibition value of 46.2% at a concentration of 1 µM.
Electronic Supplementary MaterialSupplementary material is available for this article at 10.1007/s13659-013-0028-5 and is accessible for authorized users.
Sargentodoxae Caulis was prepared from the stems of Sargentodoxa cuneata. Twenty compounds from the the stems of S. cuneata collected in Huangshan Mountain, Anhui province, were isolated and purified by column chromatography on macroporous resin (HPD100), silica gel, Sephadex LH-20 and semi-preparative HPLC. Their structures were elucidated on the basis of physico-chemical properties and spectral data analyses as (7R,8S)-3,3 '-5-trimethoxy-4,9-dihydroxy-4',7-expoxy-5',8-lignan-7'-en-9'-oic acid 4-O-beta-D-glucopyranoside(1), 1-O-(vanillic acid) -6-O-vanilloyl-beta-D-glucopyranoside(2), 4-hydroxyphenylethyl-6-O-coumaroyl-beta-D-glucopyranoside(3), citrusin B(4), cinnamoside(5), (-) -isolariciresinol 4'-O-beta-D-glucopyranoside (6), (-) -isolariciresinol 4-O-beta-D-glucopyranoside (7), 1-O-(vanillic acid) -6-(3", 5"-dimethoxy-galloyl) -beta-D-glucopyranoside (8), 4-hydroxyphenyl-ethyl-6-O-(E) -caffeoyl-beta-D-glucopyranoside (9), (-)-syringaresinol 4'-O-beta-D-glucopyranoside (10), (-)-syringaresinol di-O-beta-D-glucopyranoside (11), aegineoside (12), calceolarioside B (13), 4-hydroxy-3-methoxy-acetophenone-4-O-alpha-L-rhamnopyranosyl-(1 --> 6)-beta-D-glucopyranoside (14), 4-hydroxy-3-methoxy-acetophenone-4-O-beta-D-apiofuranosyl-(1 --> 6) -beta-D-glucopyranoside (15), (-) -epicatechin (16), salidroside (17), 3,4-dihydroxy-phenyl ethyl-beta-D-glucopyranoside (18), chlorogenic acid (19) and protocatechuic acid (20). Compound 1 was a new compound and compounds 2-7 were isolated from this plant for the first time.
Two new benzofuran lignan glycosides, gelsemiunoside A and B, were isolated from the whole plant of Gelsemium elegans Benth. Their structures were elucidated on the basis of spectroscopic evidence. Furthermore, gelsemiunoside A and B were shown a potent cytotoxic activity by suppressing the proliferation of A375-S2 cells.
A new macrolide glycoside, cuneataside F was isolated from the n-butanol extract of the stem of Sargentodoxa cuneata. The structure was elucidated on the basis of extensive 1D and 2D NMR as well as HRESI-MS spectroscopic analysis.
Three new ellagitannins named balanophotannins A-C having a 1,1'-(3,3',4,4'-tetrahydroxy)dibenzofurandicarboxyl group in their molecules and four known lignan glycosides were isolated from the extracts of fresh aboveground and underground parts of a medicinal parasitic plant Balanophora japonica (Balanophoraceae). Their structures were elucidated on the basis of spectral and chemical evidence. Chemotaxonomic significance of the known lignan glycosides in Balanophora japonica was discussed.
Balanophonin, a new neo-lignan was isolated from Balanophora japonica Makino and its structure was discussed. Structure and stereochemistry were determined by a combination of chemical method and extensive use of 1H and 13C-NMR spectrometry.
A New phenylethanoid glycoside, named tubuloside E (I), and a new neolignan glycoside, dehydrodiconiferyl alcohol γ'-O-β-D-glucopyranoside (II), were isolated from the whole plants of Cistanche tubulosa (SCHRENK)HOOK. f. (Orobanchaceae), together with dehydrodiconiferyl alcohol 4-O-β-D-glucopyranoside (III), syringalide A 3'-α-L-rhamnopyranoside (IV), isosyringalide 3'-α-L-rhamnopyranoside (V), (+)-syringaresinol O-β-D-glucopyranoside (VI), (+)-pinoresinol O-β-D-glucopyranoside (VII), liriodendrin (VIII), 6-deoxycatalpol (IX), 8-epiloganic acid (X), 20-hydroxyecdysone (XI), 8-hydroxygeraniol 1-β-D-glucopyranoside (XII) and syringin (XIII). The structure of tubuloside E (I) was established as 2-(3, 4-dihydroxyphenyl)ethyl O-α-L-rhamnopyranosyl-(1→3)-2-O-acetyl-4-O-p-coumaroyl-β-D-glucopyranoside on the basis of chemical evidence and spectral data.
Extraction of the aerial parts of Chrysolaena verbascifolia afforded a number of new piptocarphols (hirsutinolides), two new cadinanolides, two rare lignans and several common plant constituents, while the aerial parts of Lessingianthus rubricaulis furnished a new cadinanolide, vomifoliol and several triterpenes. Structures were established by high resolution NMR spectrometry. The possibility that the isolated sesquiterpene lactones are artefacts formed during the isolation process is discussed.
A new lignan glucoside has been isolated from Euphrasia rostkoviana. Its structure was elucidated by spectroscopic means and by correlation with dehydrodiconiferyl alcohol to be dehydrodiconiferyl alcohol- 4-β-d-glucoside.
Several optically pure neolignans containing a dihydrobenzo[b]furan skeleton were synthesized. Based on an X-ray crystallographic study and circular dichroism results, the absolute configurations of some naturally occurring neolignans, namely balanophonin (1), PGI2 inducer (2), dehydrodiconiferyl alcohol-4-β-d-glucoside (3), dehydroconiferyl alcohol (4) and 3′,4-di-O-methylcedrusin (5) have been unambiguously established.
A new lignan glucoside has been isolated from Euphrasia rostkoviana. Its structure was elucidated by spectroscopic means and by correlation with dehydrodiconiferyl alcohol to be dehydrodiconiferyl alcohol- 4-β-d-glucoside.
We previously reported that the extract of seeds from Aeginetia Indica L (AIL), a parasitic plant, induces potent antitumor immunity in tumor-bearing mice and that CD4+ T cells appear to be the main contributors in the induction of antitumor resistance. The present study was set up to investigate the in vitro effects of AIL on various lymphoid cells. Spleen cells from mice pretreated with AIL every 2 days for 1 week produced interleukin 2 (IL-2), interferon gamma (IFN gamma), tumor necrosis factor (TNF) and interleukin 6 (IL-6) when these cells were stimulated in vitro by AIL. Further, we found that CD4+ T cells were main producers of IL-2 and TNF upon the stimulation with ALL in vitro, while both CD4+ and CD8+ T cells secreted IFN. On the other hand, ALL was mitogenic in vitro to T enriched splenic lymphocytes as well as B enriched splenic lymphocytes. Moreover, AIL also proliferated thymocytes and this activity was potently synergistic with a suboptimal dose of concanavalin A (Con A). Lipopolysaccharide (LPS) contamination in AIL preparation was negligible since proliferative activity of AIL to B enriched splenic lymphocytes was not influenced in the presence of an endotoxin antagonist, polymyxin B sulfate (PMB). Further, B cell mitogenic activity of AIL seems to be mediated by different mechanism(s) from that of LPS since ALL could proliferate B enriched lymphocytes of C3H/HeJ mice which do not respond to the stimulation with LPS. A well known biological response modifier (BRM), Krestin (PSK), had no ability in inducing either T or B lymphocyte activation in vitro as shown by AIL.(ABSTRACT TRUNCATED AT 250 WORDS)
Three new lignans, ficusal (1) and ficusesquilignans A (2), B (3) and one new gamma-lactone, ficusolide diacetate (4), were isolated from the wood of Ficus microcarpa L.f. Their structures were determined by spectral evidence.
Table 1. Enzymatic hydrolysis of 1. Compound 1 (2 mg) was hydrolyzed with b-glucosidase (1 mg, sigma Chemical Co.) in acetate buffer The reaction mixture was extracted with EtOAc and the residue was evapd to dryness in vacuum to afford the aglycone
- Hz
Hz, H-2), 7.13 (1H, dd, J = 8.4, 1.9 Hz, H-6), 6.69 (1H,
dd, J = 15.8, 8.0 Hz, H-8¢), 5.86 (1H, d, J = 6.1 Hz, H-7), 4.83
(1H, d, J = 7.8 Hz, H-1²), 4.12 (3H, s, OMe), 4.10 (1H, m,
H-9a), 4.05 (1H, dd, J = 13.1, 5.0 Hz, H-9b), 4.03 (3H, s,
OMe), 3.85 (1H, m, H-2²), 3.66 (1H, m, H-8).
13 C-NMR
(100.0 MHz, MeOH-d 4 ): Table 1.
Enzymatic hydrolysis of 1. Compound 1 (2 mg) was hydrolyzed with b-glucosidase (1 mg, sigma Chemical Co.) in
acetate buffer (0.1 M HOAc-0.1 M NaOAc 1:2, 3 mL, pH 5.0)
for 24 hr at 37 °C. The reaction mixture was extracted with
EtOAc and the residue was evapd to dryness in vacuum to afford the aglycone, [a] D
22 -114° (c 0.1, MeOH), which was
identical with balanophonin (5) on TLC and
1 H-NMR data.
mg) was hydrolyzed with b-glucosidase (1 mg, sigma Chemical Co.) in acetate buffer (0.1 M HOAc-0.1 M NaOAc 1:2, 3 mL, pH 5.0) for 24 hr at 37°C. The reaction mixture was extracted with EtOAc and the residue was evapd to dryness in vacuum to afford the aglycone
- Hz
Hz, H-2), 7.13 (1H, dd, J = 8.4, 1.9 Hz, H-6), 6.69 (1H,
dd, J = 15.8, 8.0 Hz, H-8¢), 5.86 (1H, d, J = 6.1 Hz, H-7), 4.83
(1H, d, J = 7.8 Hz, H-1²), 4.12 (3H, s, OMe), 4.10 (1H, m,
H-9a), 4.05 (1H, dd, J = 13.1, 5.0 Hz, H-9b), 4.03 (3H, s,
OMe), 3.85 (1H, m, H-2²), 3.66 (1H, m, H-8). 13 C-NMR
(100.0 MHz, MeOH-d 4 ): Table 1.
Enzymatic hydrolysis of 1. Compound 1 (2 mg) was hydrolyzed with b-glucosidase (1 mg, sigma Chemical Co.) in
acetate buffer (0.1 M HOAc-0.1 M NaOAc 1:2, 3 mL, pH 5.0)
for 24 hr at 37°C. The reaction mixture was extracted with
EtOAc and the residue was evapd to dryness in vacuum to afford the aglycone, [a] D
22 -114°(c 0.1, MeOH), which was
identical with balanophonin (5) on TLC and 1 H-NMR data.
Aegineoside (2)
Pale yellow powder, mp 262-264°C. [a] D
22 -56.7
- J G Chai
- T Bando
- S Konashi
- S Ohkubo
- M Oka
- H Nagasawa
- K Himeno
- M Sato
Chai, J. G.; Bando T.; Konashi, S.; Ohkubo, S.; Oka, M.;
Nagasawa, H.; Himeno, K.; Sato, M. Proc. Jpn. Soc.
Immunol. 1990, 20, 317.
- J G Chai
- T Bando
- H Nagasawa
- K Himeno
- M Sato
- S Ohkubo
Chai, J. G.; Bando, T.; Nagasawa, H.; Himeno, K.; Sato, M.;
Ohkubo, S. Immunopharmacology 1994, 27, 13.
- S S Dighe
- A B Kulkarni
Dighe, S. S.; Kulkarni, A. B. Indian J. Chem. 1974, 12, 413.
- S S Dighe
- S V Manerikar
- A B Kulkarni
Dighe, S. S.; Manerikar, S. V.; Kulkarni, A. B. Indian J.
Chem., Sect. B. 1977, 15B, 546.
- T Endo
- H Taguchi
- H Sasaki
- I Yoshioka
Endo, T.; Taguchi, H.; Sasaki, H.; Yoshioka, I. Chem.
Pharm. Bull. 1979, 27, 1807.
- S K Chaudhuri
- O Sticher
Chaudhuri, S. K.; Sticher, O. Phytochemistry 1981, 20,
2603.
- T Kikuchi
- S Matsuda
- S Kadota
- T Tai
Kikuchi, T.; Matsuda, S.; Kadota, S.; Tai, T. Chem. Pharm.
Bull. 1985, 33, 3985.
- F Yoshizawa
- N Deyama
- N Takizawa
- K Usmanghani
- M Ahmad
Yoshizawa, F.; Deyama, N.; Takizawa, N.; Usmanghani, K.;
Ahmad, M. Chem. Pharm. Bull. 1990, 381, 1927.
- B S Montanaro
- C A N Catalan
- J G Diaz
- W Herz
Montanaro, B. S.; Catalan, C. A. N.; Diaz, J. G.; Herz, W.
Phytochemistry 1993, 34, 253.
- Y C Li
- Y H Kuo
Li, Y. C.; Kuo, Y. H. Chem. Pharm. Bull. 2002, 48, 1862.
- M S M Yuen
- F Xue
- T C W Mak
- H N C Wong
Yuen, M. S. M.; Xue, F.; Mak, T. C. W.; Wong, H. N. C. Tetrahedron 1998, 54, 12429.