Soil bacterial hydrolysis leading to genuine aglycone—VIII : Structures of a genuine sapogenol protobassic acid and a prosapogenol of seed kernels of Madhuca longifolia L.

By virtue of the soil bacterial hydrolysis method, a genuine sapogenol named protobassic acid was obtained from the saponins of seed kernels of Madhuca longifolia L. (Sapotaceae), and the structure has been established as 2β, 3β, 6β, 23-tetrahydroxy-olean-12-en-28-oic acid (2a). In addition, the structure of a prosapogenol designated as Mi-glycoside I, which was isolated concurrently during the above microbiological procedure, has been elucidated as 3-0-β-d-glucopyranosyl-protobassic acid (3a). It has been suggested that protobassic acid (2a) may be a common sapogenol of several sapotaceous plants in place of hitherto approved bassic acid (1a).     

New C19-diterpenoid alkaloids from the parent roots of Aconitum carmichaelii

Aconitum carmichaelii is a widely used traditional Chinese medicine and important source of clinical drugs. The parent roots of A. carmichaelii were investigated resulting in the isolation and identification of five new C₁₉-diterpenoid alkaloids; 14α-benzoyloxy-N-ethyl-15α-hydroxy-1α,6α,8β,16β,18-pentamethoxyaconitane formate (1), 14α-benzoyloxy-8β-butoxy-N-ethyl-13β,15α-dihydroxy-1α,6α,16β,18-tetramethoxyaconitane formate (2), 14α-benzoyloxy-8β-butoxy-N-ethyl-3α,13β,15α-trihydroxy-1α,6α,16β,18-tetramethoxylaconitane (3), 14α-benzoyloxy-8β-butoxy-3α,13β,15α-trihydroxy-1α,6α,16β,18-tetramethoxyl-N-methylaconitane (4) and 8β,14α-dibenzoyloxy-N-ethyl-13β,15α-dihydroxy-1α,6α,16β,18-tetramethoxyaconitane (5).     

Three New Myrsinol Diterpenes from <em>Euphorbia prolifera</em> and Their Neuroprotective Activities

Three new myrsinol diterpenes were isolated from the roots of Euphorbia prolifera. Their structures were elucidated as 2α-O-isobutyryl-3β,5α,7β,10,15β-penta-O-acetyl-14α-O-benzoyl-10,18-dihydromyrsinol (1), 2α-O-isobutyryl-3β-O-propion-yl-5α,7β,10,15β-tetra-O-acetyl-10,18-dihydromyrsinol (2), and 2α,14α-di-O-benzoyl-3β,5α,7β,10,15β-penta-O-acetyl-10,18-dihydromyrsinol (3) on the basis of spectroscopic data analyses (IR, ESI-MS, HR-ESI-MS, and 1D and 2D NMR). Their neuroprotective activities were evaluated and compounds 1 and 2 showed neuroprotective effects against MPP⁺-induced neuronal cell death in SH-SY5Y cells.     

Asymmetric halolactonisation reaction-2 : Elucidation of general applicability and mechanism of the asymmetric bromolactonisation reaction

Detailed studies on the asymmetric bromolactonisation were carried out by employing several structural types of α,β-unsaturated acids (2) as reaction substrates and various (S)-α-amino acids as chiral sources.Following several novel aspects of the asymmetric bromolactonisation were uncovered by combining the results obtained in this study with those of the previous report. Thus, the bromolactonisation of (S)-N-(cis(E)-α,β-disubstituted-α,β-unsaturat acylproline((S)-3a,b) proceeds more stereoselectively than that of the trans(Z)-α,β-disubstituted analogue ((S)-3c), to give the 6-membered bromolactone(4A) via the symmetrical and/or the carbocationic bromonium ions (5AB and/or 5AC). While (S)-N-(trans(E)-β-monosubstituted-α,β-unsaturated)acyl-proline((S)-3d) undergoes no bromolactonisation, (S)-N-(β,β-disubstituted-α,β-unsaturated)acylproline((S)-3e) regiospecifically gives the 7-membered bromolactone(11e) via the carbocationic bromonium ion(5AA) when submitted to the bromolactonisation. (S)-Proline((S)-8) is found to the superior chiral source for the asymmetric bromolactonisation among those examined.     

Synthesis, Antigenicity Against Human Sera and Structure-Activity Relationships of Carbohydrate Moieties from <em>Toxocara</em> larvae and Their Analogues

Stereocontrolled syntheses of biotin-labeled oligosaccharide portions containing the Galβ1-3GalNAc core of the TES-glycoprotein antigen obtained from larvae of the parasite Toxocara and their analogues have been accomplished. Trisaccharides Fuc2Meα1-2Gal4Meβ1-3GalNAcα1-OR (A), Fucα1-2Gal4Meβ1-3GalNAcα1-OR (B), Fuc2Meα1-2Galβ1-3GalNAcα1-OR (C), Fucα1-2Galβ1-3GalNAcα1-OR (D) and a disaccharide Fuc2Meα1-2Gal4Meβ1-OR (E) (R = biotinylated probe) were synthesized by block synthesis using 5-(methoxycarbonyl)pentyl-2,3,4,6-tetra-O-acetyl-β-D-galactopyranosyl-(1?3)-2-azide-4-O-benzyl-2-deoxy-α-D-galactopyranoside as a common glycosyl acceptor. We examined the antigenicity of these five oligosaccharides by enzyme linked immunosorbent assay (ELISA). Our results demonstrate that the O-methyl groups in these oligosaccharides are important for their antigenicity and the biotinylated oligosaccharides A, B, C and E have high serodiagnostic potential to detect infections caused by Toxocara larvae.     

First synthesis of 5,6-branched galacto-hexasaccharide,the dimer of the trisaccharide repeating unit of the cell-wall galactans of Bifidobacterium catenulatum YIT 4016

α-d-Galactopyranosyl-(1→6)-[β-d-galactofuranosyl-(1→5)]-β-d-galactofuranosyl-(1→6)-β-d-galactofuranosyl-(1→5)-[α-d-galactopyranosyl-(1→6)]-β-d-galactofuranose, the dimer of the trisaccharide repeating unit of the cell-wall galactans of Bifidobacterium catenulatum YIT 4016, has been synthesized as its dodecyl glycoside 2 by coupling of 2,3,4,6-tetra-O-benzyl-α-d-galactopyranosyl-(1→6)-[6-O-acetyl-2,3,5-tri-O-benzoyl-β-d-galactofuranosyl-(1→5)]-2-O-acetyl-3-O-benzyl-β-d-galactofuranosyl trichloroacetimidate 14 with dodecyl 2,3,4,6-tetra-O-benzyl-α-d-galactopyranosyl-(1→6)-[2,3,5-tri-O-benzoyl-β-d-galactofuranosyl-(1→5)]-2-O-acetyl-3-O-benzyl-β-d-galactofuranoside 16. The trisaccharide trichloroacetimidate donor 14 and trisaccharide acceptor 16 were regiospecifically prepared by employing 3-O-benzyl-1,2-O-isopropylidene-α-d-galactofuranose 4 as the glycosyl acceptor, and isopropyl 2,3,4,6-tetra-O-benzyl-1-thio-β-d-galactopyranoside 5 and 6-O-acetyl-2,3,5-tri-O-benzoyl-β-d-galactofuranosyl trichloroacetimidate 9 as glycosyl donors.     

Steroide—XL: 16,17-azido- und 16,17-aminoalkohole des östra-1,3,5(10)-trien-3-methyläthers

The four epimeric azido alcohols of estra-1,3,5(10)-trien-3-methyl ether with nitrogen at C-16 and oxygen at C-17 were prepared by the following reactions: cleavage of the 16α,17α-epoxide 1 with sodium azide affords the 16β,17α-azido alcohol 2a. The analogous reaction of the 16β,17β-epoxide 4 gives the 17α,16β-azido alcohol 5a and the desired 16α,17β-azido alcohol 6a in low yield. 6a is obtained in a smooth reaction by substitution of the 16β,17β-bromohydrine 8 with sodium azide. Sodium borohydride reduction of the 16β-azido-17-ketone 9 yields the 16β,17β-azido alcohol 10a, reduction of 16α-azido-17-ketone 13 with lithium borohydride gives the 16α,17α-azido alcohol 14a. From the azido alcohols the corresponding amino alcohols 3a, 7a, 11a and 15a are prepared with hydrazine hydrate/Raney nickel. The amino alcohols give the acetic anhydride the corresponding acetylamino alcohols. The cis-amino alcohols 11a and 15a react with acetone to the corresponding oxazolidines 12 and 16.     

Terpenoids—LXXI: Chemical studies of marine invertebrates—XIV. Four representatives of a novel sesquiterpene class—the capnellane skeleton

The isolation and complete structure determination of four marine sesquiterpenoids: Δ⁹⁽¹²⁾-capnellene-8β,10α-diol (1), Δ⁹⁽¹²⁾-capnellene-3β,8β,10α-triol (3), Δ⁹⁽¹²⁾-capnellene-5α,8β,10α-triol (5), Δ⁹⁽¹²⁾-capnellene-2ξ,8β,10α-triol (7) from the soft coral Capnella imbricata is described. These alcohols are the first members of a fundamentally new sesquiterpene class consisting of three 5-membered fused rings which we have named capnellane (A).     

Diterpenes from the marine pulmonate trimusculus reticulatus

The marine pulmonate Trimusculus reticulatus contains 6β-isovaleroxylabda-8,13-dien-7α,15-diol (1) and 2α,7α-diacetoxy-6β-isovaleroxylabda-8,13-dien-15-ol (2). The diol 1 is found in the mucus produced by T. reticulatus that repels predatory sea stars.     

Specific oxidation of C-14 oxygenated 4(20),11-taxadienes by microbial transformation

Three C-14 oxygenated taxanes, 2α,5α,10β,14β-tetraacetoxytaxa-4(20),11-diene (1), 2α,5α,10β-triacetoxy-14β-(2-methylbutyryloxy)taxa-4(20),11-diene (2), and yunanaxane (3), major products of callus cultures of Taxus spp., were regio- and stereoselectively hydroxylated at the 7β position by a fungus, Absidia coerulea IFO 4011. Intriguingly, when 1 was co-administered with β-cyclodextrin and incubated with the fungus cell cultures, three other compounds 5α,9α,10β,13α-tetraacetoxytaxa-4(20),11-dien-14β-ol (7), 5α,9α,10β,13α-tetraacetoxytaxa-4(20),11-dien-1β-ol (8) and 5α,9α,10β,13α-tetraacetoxy-11(15→1) abeotaxa-4(20),11-dien-15-ol (9) were obtained.     

A new eudesmane sesquiterpene glycoside from Parepigynum funingense

A new eudesmane sesquiterpene glycoside,1α,6β-dihydroxy-5,10-bis-epi-eudesm-4(15)-ene-6-O-β-D-glucopyranoside(2), together with a known analogue compound,1α,6β-dihydroxy-5,10-bis-epi-eudesm-3-ene-6-O-β-D-glucopyranoside(1),were isolated from the roots of Parepigynumfuningense.The structure of 2 was determined by 1D and 2D NMR spectroscopy.Compound 1 was isolated from this plant for the first time.     

N-Nosyl as a stereoselectivity-improving and easily removable group in the O-glycosylation of d-allal and d-galactal-derived allyl aziridines. Stereospecific synthesis of 4-amino-2,3-unsaturated-O-glycosides

The glycosylation of alcohols, phenol, and partially protected monosaccharides with the diastereoisomeric d-allal and d-galactal-derived N-nosyl aziridines 2α and 2β leads to the corresponding 4-N-(nosylamino)-2,3-unsaturated-α-O- (6α) and β-O-glycosides and disaccharides (6β), respectively, in a stereospecific substrate-dependent O-glycosylation process. The N-(nosylamino) group of 6α and 6β can easily be deprotected to give the corresponding 4-amino-2,3-unsaturated-O-glycosides 7α and 7β, with an increased value to our glycosylation protocol.     

Stereoselective synthesis of novel N-(α-l-arabinofuranos-1-yl)-l-amino acids

In lead detoxification, the α-anomer of N-glycocyl-l-amino acid is more potent than its β-anomer. Here a six-step-reaction route for stereoselectively preparing N-(α-l-arabinose-1-yl)-l-amino acids is reported. Treating l-arabinose with acetic anhydride and sodium acetate provided 1,2,3,5-tetra-O-acetyl-l-arabinofuranose in 90% yield. After removing the 1-acetyl group, the thus formed 2,3,5-tri-O-acetyl-l-arabinofuranose and N-(2-nitrophenylsulfonyl)-l-amino acid t-butylesters were treated with triphenylphosphine to perform Mitsunobu dehydration and form 2,3,5-tri-O-acetyl-l-arabinofuranosyl-l-[N-(2-nitrophenylsulfonyl)]amino acid t-butylesters 2a–f, and the ratios of their α- to β-anomer ranged from 8/1 to 9/1. Chromatographic separation provided epimerically pure 2a–f-α and 2a–f-β. In the presence of CF₃CO₂H, 2a–f-α and 2a–f-β were converted to α- and β-anomers of N-(2,3,5-tri-O-acetyl-l-arabinofuranosyl)-N-(2-nitrobenzenesulfonyl)-l-amino acids, 3a–f-α and 3a–f-β, in 87–92% yields. While in the presence of NaOCH₃, 3a–f-α and 3a–f-β were converted to α- and β-anomers of N-(l-arabinofuranosyl)-N-(2-nitrobenzenesulfonyl)-l-amino acids, 4a–f-α and 4a–f-β, in 90–96% yields. Treating 4a–f-α and 4a–f-β with N-ethyldiisopropylamine (DIPEA) and thiophenol, their 2-nitrophenylsulfonyl groups were removed, and the α- and β-anomers of N-(l-arabinose-1-yl)-l-amino acids were formed in 70–79% yields. The bioassay confirmed that the lead detoxification activity of the α-anomer was significantly higher than that of the β-anomer.     

Officinatrione: an unusual (17S)-17,18-seco-lupane skeleton,and four novel lupane-type triterpenoids from the roots of Taraxacum officinale

Novel 5 lupane-type of triterpenois, i.e., 3β-acetoxy-18α,19α-epoxylupan-21β-ol (1), 18α,19α-epoxy-21β-hydroxylupan-3-one (2), lup-18-ene-3,21-dione (3), lupa-18,21-dien-3β-yl acetate (4), and (17S)-17,18-seco-lup-19(21)-ene-3,18,22-trione (5), named officinatrione, as well as 16 known compounds from the roots of Taraxacum officinale collected in Takatsuki city, Osaka, Japan. Of the above compounds, 5 was the first lupane-type triterpene, of which the D-ring was open to form a nine-membered ring. Compounds 2 and 5 exhibited moderate cytotoxic activities against L1210 cell line (IC₅₀ 10.5 and 10.1 μM).     

Four new eremophilendiolides from Ligularia atroviolacea

From Ligularia atroviolacea, four new eremophilendiolides, 81$-hydroxy-eremophil-3,7 （11）-dien-12,8α（14,6α）-diolide （1）, 8β-methoxy-eremophil-3,7（11）-dien-12,8α（14,6α）-diolide （2）, 8α-hydroxy-eremophil-3,7（11）-dien-12,8lβ（14,6α）-diolide （3） and eremophil-3,7（11）,8-trien-12,8 （14,6α）-diolide （4）, as well as a known diolide （5） were isolated. Their structures were elucidated on the basis of 1D and 2D NMR as well as ESI-MS spectral data.     

Structural characterization of saturated pyrrolizidine alkaloids from Heliotropium transalpinum var. transalpinum Vell by NMR spectroscopy and theoretical calculations

The chemical investigation of Heliotropium transalpinum var. transalpinum Vell. (Boraginaceae) led to the isolation of transalpinecine (1), a novel pyrrolizidine alkaloid, in addition to known alkaloids subulacine (1β-2β-epoxy-1α-hydroxymethyl-8α-pyrrolizidine) (2), and 1α-2α-epoxy-1β-hydroxymethyl-8α-pyrrolizidine (3). The structures of the isolated compounds were elucidated based on spectroscopic data and theoretical calculations.     

A new triterpene and a saponin from Centella asiatica

A new triterpene and a saponin,named 2α,3β,23-trihydroxyurs-20-en-28-oic acid(1)and 2α,3β,23-trihydroxyurs-20-en-28-oic acid O-α-L-rhamnopyranosyl-(1→4)-O-β-D-glucopyranosyl-(1→6)-O-β-D-glucopyranosyl ester(2),have been isolated from the aerial part of Centella asiatica.Their structures were elucidated by spectral methods,including 2D-NMR spectra.     

Biotransformation of two stemodane diterpenes by Mucor plumbeus

The microbiological transformation of 13α,17-dihydroxy-stemodane (2) by the fungus Mucor plumbeus afforded 13α,17,19-trihydroxy-stemodane (3), 3β,13α,17-trihydroxy-stemodane (5), 3-oxo-13α,17-dihydroxy-stemodane (7), 7α,13α,17,19-tetrahydroxy-stemodane (8), 3β,11α,13α,17-tetrahydroxy-stemodane (10), 3β,7α,13α,17-tetrahydroxy-stemodane (12), 3β,8β,13α,17-tetrahydroxy-stemodane (14), 2α,13α,17-trihydroxy-stemodane (16), 2α,13α,17,19-tetrahydroxy-stemodane (17), 2α,3β,13α,17-tetrahydroxy-stemodane (20) and 3β,11β,13α,17-tetrahydroxy-stemodane (22), whilst the incubation of 13α,14-dihydroxy-stemodane (25) gave 3β,13α,14-trihydroxy-stemodane (28), 2α,13α,14-trihydroxy-stemodane (29) and 13α,14,19-trihydroxy-stemodane (30). Preference for hydroxylations of ring A at C-2(α), C-3(β) and C-19 were observed in both incubations. An interesting rearrangement of 13α,14α-dihydroxy-stemodanes to 14-oxo derivatives with an unusual carbon framework has been observed under acetylation conditions. We have named this skeleton prestemodane, which, as a hydrocarbon ion, had been postulated as a biogenetic precursor of stemodane.     

Two New Daucane Sesquiterpenoids from <em>Daphne aurantiaca</em>

Two new daucane sesquiterpenoids 1β,2β-epoxy-10(H)α-dauca-11(12)-ene-7α,14-diol (1) and 1α,2α-epoxy-10(H)α-dauca-11(12)-ene-7α,14-diol (2) were isolated from the plateau medicinal plant Daphne aurantiaca Diels. (Thymelaeceae). Their structures were elucidated by 1D and 2D NMR spectroscopy, as well as HR-ESI-MS data.     

An enantiomerically pure bilirubin. Absolute configuration of (αR,α′R)-dimethylmesobilirubin-XIIIα

Enantiomerically pure (+)-(αR,α′R)-dimethylmesobilirubin-XIIIα 1 and its (αS,α′S) enantiomer ent-1 were synthesized in ten steps from simple precursors. Resolution was achieved at an early stage in the synthesis, with a racemic monopyrrole precursor rac-6 being converted to its amides 8 with (1S)-camphor-2,10-sultam. Resolution of 8 to 99% d.e. was accomplished in three crystallizations, and the absolute configuration of the acid 6 was deduced by X-ray crystallography of the more crystalline, diastereomerically pure amide 7. Circular dichroism spectroscopy of 1 showed intense bisignate Cotton effects: Δε^max₄₃₅=+344, Δε^max₃₉₁=−193 (CHCl₃), as expected for a molecular exciton, and consistent with a P-helical intramolecularly hydrogen-bonded ridge-tile conformation. The Cotton effect magnitudes of 1 match almost exactly those found for (−)-(βS,β′S)-dimethylmesobilirubin-XIIIα 11 and (+)-(αR,β′R)-dimethylmesobilirubin-XIIIα. However, the Cotton effect of the pseudo-meso diastereomer (αR,β′S)-dimethylmesobilirubin-XIIIα 12 is not zero. Its large positive exciton couplet and ¹H NMR NOE analysis confirm that an α-CH₃ exerts a greater steric demand than a β-CH₃—by a factor of ∼3.