Steroidal analogues of unnatural configuration—X : Synthesis of 9-methyl-19-nor-9β,10α-progesterone

The reaction of 3,3-ethylenedioxy-9-methyl-9β-oestr-5(10)-en-17-one (4) with tosylmethyl isocyanide and base afforded the 17β- and 17α-carbonitriles (5 and 6). Treatment of the 17β-epimer (5) with methyl lithium gave, after hydrolysis, 9-methyl-19-nor-9β-pregn-5(10)-ene-3,20-dione (8). The same reaction sequence employed on 3,3; 5,5-bisethylenedioxy-9-methyl-4,5-seco-9β,10α-oestr-17-one (12), with subsequent cyclization, yielded the 5β-hydroxy-3,20-diketones (17 and 18) as well as 9-methyl-19-nor-9β,10α-progesterone (19) and its 17α-epimer (20).     

Bioactive compounds from the scale insect fungus Conoideocrella tenuis BCC 44534

Eleven new compounds, including two quinone derivatives of bioxanthracene, conoideocrellones A (1) and B (2), two bioxanthracenes 3 and 4, four isocoumarins and isocoumarin glycosides 7–10, two phenolic compounds 16 and 17, and a diterpenoid compound, conoideocin A (18), were isolated from culture of the scale-insect pathogenic fungus Conoideocrella tenuis BCC 44534. Seventeen known compounds, compounds 5 and 6, ES-242-2 and its atropisomer, isocoumarins and isocoumarin glycosides 11–15, 3,4,6-trihydroxymellein, cis-4,6-dihydroxymellein, metarhizins A (19) and B (20), BR-050 (21), 5α,8α-epidioxy-24(R)-methylcholesta-6,22-dien-3β-ol, zeorin, and conoideocrellide A, were also isolated from this fungus. Structures of these compounds were elucidated by NMR and MS data analyses. Compound 4 was active against Plasmodium falciparum K1 (IC₅₀ 6.6?μg/mL), while it did not show cytotoxicity. Conoideocrellone A (1) and compounds 3 and 7 exhibited cytotoxic activity, while conoideocin A (18) showed broad range of biological activities including antimalarial, antibacterial, and cytotoxic activities.     

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.     

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).     

Tetracyclic triterpenoids isolated from semi-mangrove plant Hibiscus tiliaceus

A continuing phytochemical study on the semi-mangrove plant Hibiscus tiliaceus yielded two new tetracyclic triterpenoids （3β,24S）-19（10→9）-abeo-8α,9β,10α-eupha-5,25（26）-dien-3,24-diol （tiliacol A, 1 ）, and （3β,23Z）-19（10→9）-abeo-8α,9β,10α-tircalla-5,23-dien-3,25-diol （tiliacol B, 3）, together with one known analog （2）. Their structures were elucidated on the basis of extensive spectral analyses （MS, IR, 1D NMR and 2D NMR） and comparison with literature compounds. Compound 2 showed potent cytotoxicity against both P388 and HeLa cells with ICon values of 11.2 μmol/L and 11.5 μmol/L, resoectively.     

Studies on asterosaponins—V : A novel steroid conjugate, 5α-pregn-9(11)-ene-3β,6α-diol-20-one-3-sulfate,from a starfish saponin,asterosaponin A

A new crystalline steroid conjugate was obtained by partial acid hydrolysis of asterosaponin A, a steroidal saponin from the starfish, Asterias amurensis. The structure of the conjugate was established as 5α-pregn-9(11)-ene-3β,6α-diol-20-one-3-sulfate (2) on the basis of elemental analysis, IR and PMR spectra measurement and chemical reaction. Solvolysis of compound 2 yielded 5α-pregn-9(11)-ene-3β,6α-diol-20-one. Oxidation with chromium trioxide-pyridine complex followed by solvolysis afforded a new steroid, 5α-pregn-9(11)-ene-3β-ol-6,20-dione, whose structure was deduced by the measurement of ORD curve and PMR spectra. Thus, the location of carbohydrate moiety in asterosaponin A has been assigned to 6α-hydroxy group of the steroid conjugate.     

New serratane triterpenes from western white pine bark

Three new serratanes were isolated from the nonsaponifiable fraction of western white pine ($\text{Pinus monticola}$ Dougl.) bark. The compounds were shown to be 3β-methoxyserrat-14-ene-21α,30-diol ($\text{8a}$), 3β-methoxyserrat-14-ene-21α, 29-diol ($\text{9a}$), and 3β-methoxyserrat-14-ene-21β,30-diol ($\text{10a}$), by a combination of chemical, and spectral methods.     

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.     

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.     

Structure of marsileagenin a; A new hexahydroxy triterpene from marsilea minuta linn

The crude saponin obtainable from Marsilea minuta Linn on acid hydrolysis yielded a mixture of sapogenols. The major sapogenol named Marsileagenin A was found to be a hexahydroxy triterpene of oleanene series. From a study of various spectrometric data together with chemical reactions the structure of this sapogenol has been assigned as olean-12-ene-2α, 3β, 16β, 21β, 22α, 28-hexol (1a).     

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.     

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.     

Proanthocyanidin glycosides from the leaves of Quercus ilex L. (Fagaceae)

From the polar extracts of the leaves of Quercus ilex L., two new proanthocyanidin glycosides, namely afzelechin-(4α→8)-catechin-3-O-β-glucopyranoside (1) and afzelechin-(4α→8)-catechin-3-O-α-rhamnopyranoside (2), were isolated in addition to catechin (3), proanthocyanidin B₃ (4), prodelphinidin C (5), dehydrodicatechin A (6), quercetin (7) and six known flavonol glucosides with their acylated derivatives (8-13) and ellagic acid (14). The structures of all isolated compounds were established by spectroscopic means, mainly 1D and 2D NMR, as well as LC/MS and HR-MS spectrometric analyses. The absolute configuration of compound 1 was determined by CD measurements. The proanthocyanidin glycosides are especially interesting, as they possess the sugar in the upper unit of the dimer, which is rare for this type of compounds.     

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.     

Triterpene glycosides of Thalictrum squarrosum. III. Structures of squarrogenins 1 and 2

Two genins — squarrogenin 1 and squarrogenin 2 — have been isolated from nodding meadow rue by the hydrolysis of squarrosides A1 and A2. The compounds are epimeric at C-21 and have the following structures: 1 — (21R, 22S, 23R)-21-methoxy-21,23-epoxycycloart-24-ene-3β,22β-30-triol, C₃₁H₅₀O₅, mp 169–171°C (hexane-acetone), [α] ₅₄₆ ²⁰ ?11.06° (c 4.52; pyridine); and 2 — (21S, 22S, 23R)-21-methoxy-21,23-epoxycycloart-24-ene-3β,22β,30-triol, C₃₁H₅₀O₅, mp 190–193°C (hexane-acetone), [α] ₅₄₆ ²⁰ +106.6° (c 0.3; pyridine). The results of¹H and¹³C NMR spectroscopy and of mass spectrometry for the new compounds are given.     

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.     

Activité antiplasmodiale in vitro des composés isolés des écorces du tronc de Vitex thyrsiflora

Phytochemical study of Vitex thyrsiflora (Verbenaceae), a medicinal plant commonly used in traditional medicine to treat malaria, have allowed to isolate six compounds identified 20(R),24(E)-3-Oxo-9β-lanosta-7,24-dien-26-oic acid (1), α-amyrin (2), β-amyrin (3), friedelin (4), β-sitosterol palmitate (5) and a sterol glucoside (6). All these compounds were isolated for the first time in this plant. Their structures were determined on the basis of their physical and spectroscopic data (IR, MS, UV, NMR) and by comparison of these data with those reported in the literature. Compound 5 showed significant antiplasmodial activity with IC₅₀ of 3,09 and 8,98 μg/mL against multi-resistant strains Dd2 and K1 of P. falciparum. All these constituents were isolated from this plant for the first time. The tested compounds were non-cytotoxic on the LLC-MK2 monkey kidney epithelial cells. The results obtained can justify the use of Vitex thyrsiflora stem bark in traditional medicine for the treatment of malaria.     

Diastereoselective synthesis of antiquorin and related polyoxygenated atisene-type diterpenes

A diastereoselective approach to polyoxygenated atisene-type diterpenes starting from (S)-(+)-carvone is described. The key steps used in the preparation of the atisene framework are an intramolecular Diels-Alder reaction, an intramolecular diazoketone cyclopropanation, an endocyclic cyclopropane ring cleavage and the regioselective reduction of an allylic bromide by a low-valent chromium species. The synthesis of natural atisanes antiquorin (1), atis-16-ene-3,14-dione (3), atis-16-ene-2,3,14-trione (8) and 3β-hydroxy-atis-16-ene-2,14-dione (9) following this approach is presented. Also described is the synthesis of 18-hydroxy-atis-16-ene-3,14-dione (5), the structure erroneously assigned to an atisene isolated from the Fijian plant Euphorbia fidjiana. This work shows that the natural atisene isolated from this plant is, in fact, the epimer at C-4 of this compound.     

Antibacterial activity of flavonoids and triterpenoids isolated from the stem bark and sap of Staudtia kamerunensis Warb. (Myristicaceae)

The chemical investigation of the ethyl acetate extract of the stem bark of Staudtia kamerunensis and sap led to the isolation of six compounds which included three isoflavonoids: biochanin A (1), formononetin (2) and 3-(1,3-benzodioxol-5-yl)-5,6,7-trimethoxy-4H-1-benzopyran-4-one (3), one flavonoid: (-) epicatechin (4) and two pentacyclic triterpenoids (oleanan-12-ene-2α,3β -diol (5) and 2α,3β-dihydroxylup-20-ene (6). They were characterized by HREIMS (High Resolution Electron Ionisation Mass Spectrometry), NMR spectroscopy (1D and 2D) and comparison with existing data in literature. The crude extract and isolates were tested against twelve bacterial strains namely; Bacillus subtilis, Staphylococcus epidermidis, Enterococcus faecalis, Mycobacterium smegmatis, Staphylococcus aureus, Enterobacter cloacae, Klebsiella oxytoca, Pseudomonas aeruginosa, Proteus vulgaris, Escherichia coli, Proteus mirabilis and Klebsiella pneumonia. Streptomycin, nalidixic acid and ampicillin were used as standard antibacterial drugs. The results revealed significant antibacterial activity for both the ethyl acetate partition and for the tested compounds, with the lowest MIC value being 15.625 μg/mL. A synergistic activity of the isolated triterpenoids was evaluated with interesting results. On a general note, the antibacterial activity of compound 5 was doubled specifically against Gram-negative bacterial strains. This could be a therapeutic antimicrobial pathway in face of the rising bacterial resistance. To the best of our knowledge, it is the first time that flavonoids and triterpenoids are isolated from this genus and species. It is also the first report of antibacterial studies on this species.     

Synthesis of di- and tetra-hydroaldosterone derivatives and the C19 position isomer of 3α,5β-tetrahydroaldosterone

Crystalline 5β-dihydroaldosterone diacetate (3b) was prepared and converted into 3α,5β- and 3β,5β-tetrahydroaldosteroné (5a and 4a). 19-Oxygenated compounds were obtained by photolysis of compound B- 3,21-diacetate-11-nitrite (10b).