First evidence that cytochrome P450 may catalyze both S-oxidation and epoxidation of thiophene derivatives

Oxidation of 2-phenylthiophene (2PT) by rat liver microsomes, in the presence of NADPH and glutathione (GSH), led to three kinds of metabolites whose structures were established by 1H NMR and mass spectrometry. The first ones were 2PT-S-oxide dimers formed by Diels-Alder type dimerization of 2PT-S-oxide, while the second ones were GSH adducts derived from the 1,4-Micha?l-type addition of GSH to 2PT-S-oxide. The third metabolites were GSH adducts resulting from a nucleophilic attack of GSH to the 4,5-epoxide of 2PT. Oxidation of 2PT by recombinant, human cytochrome P4501A1, in the presence of NADPH and GSH, also led to these three kinds of metabolites. These results provide the first evidence that cytochrome P450 may catalyze the oxidation of thiophene compounds with the simultaneous formation of two reactive intermediates, a thiophene-S-oxide and a thiophene epoxide.     

Furanoheliangolides and other compounds from Calea hymenolepis

Calea hymenolepis afforded in addition to known compounds two new furanoheliangolides, one being a Diels-Alder adduct with myrcene, a p-hydroxyacetophenone derivative and two dimeric ones, again being formal Diels-Alder adducts. The structures were elucidated by highfield ¹H NMR spectroscopy.     

Three new immunomodulating C21-steroidal glycosides from the stems of Stephanotis mucronata

Three new C(21)-steroidal glycosides stemucronatosides H, I, and J (1-3, resp.) were isolated from the stems of Stephanotis mucronata, together with three known compounds sinomarinoside A (4), sinomarinoside E (5), and stephanoside H (6). These isolated compounds were tested for their immunological activities in vitro against concanavalin-A(Con A)- and lipopolysaccharide(LPS)-induced proliferation of mice splenocytes. Compounds 3, 4, and 6 showed immunosuppressive activities in a dose-dependent manner, while compounds 1, 2, and 5 possessed immunoenhancing activities.     

Diels-Alder type adducts from Morus cathayana.

Two natural Diels-Alder type adducts, cathayanon A (1) and cathayanon B (2), resembling sanggenon C (4) and O (3), were isolated from the root bark of Morus cathayana. Their structures were elucidated on the basis of spectroscopic evidence. The structure of 1 was confirmed by the results of X-ray crystallographic analysis. The absolute configurations of 1 and 2 were determined as 2S, 3R,14S, 19S, 20R and 2S, 3R, 14R, 19S, 20R, respectively. The absolute configurations at C-2 and C-3 of two other known isomeric Diels-Alder adducts sanggenon O (3) and C (4) were deduced as 2R, 3S. Pharmacological tests indicated that 1 and 2 exhibited potent activities on the inhibition of HL-60 cell adhesion to BAEC at concentrations of 10(-5) mol l(-1), with inhibitory rates of 44.72 and 39.02%, respectively.     

Seven new vernocuminosides from the stem bark of Vernonia cumingiana Benth

Seven new stigmastane-type steroidal glycosides, vernocuminosides H-N, have been isolated from the stem bark of Vernonia cumingiana Benth. The structures of these compounds were determined by NMR spectrometric methods including HSQC, HMBC, ¹H-¹H COSY, and NOE, as well as circular dichroism experiments. Anti-inflammatory activities of vernocuminosides I and K-N were determined.     

长穗桑中的Diels-Alder型加合物

从长穗桑的茎皮中首次分离到9个Diels—Alder型加合物,通过NMR、MS等波谱分析手段分别鉴定为mulberrofuran K（1）,mulberrofuran G（2）,guangsangon L（3）,kuwanon J（4）,kuwanonx（5）,guangsangonG（6）,guangsangon B（7）,guangsangon D（8）,kuwanon P（9）。化合物1—9进行了抗氧化活性筛选。结果表明,在10^-5M浓度下,化合物1,2,5—7,9对Fe^2＋-半胱氨酸诱导的肝微粒体脂质过氧化产生的丙二醛（malondialdehyde,MDA）有抑制作用（抑制率大于50％）。     

Cryptoporic and isocryptoporic acids from the fungal cultures of Polyporus arcularius and P. ciliatus

In a chemical study of several fungal cultures of Polyporus, a methyl ester of cryptoporic H was isolated from P. ciliatus, together with cryptoporic acid H and 5-hydroxymethylfuran-3-carboxylic acid. Furthermore, two additional compounds, named isocryptoporic acids H and I, were isolated from P. arcularius. These isocryptoporic acids are isomers of the cryptoporic acids with drimenol instead of albicanol as the terpenoid fragment; their structural elucidation was determined by application of spectroscopic methods.     

Guaiane dimers from Xylopia vielana

From the leaves of Xylopia vielana (Annonaceae) two dimeric guaianes named vielanins D and E were isolated and structurally elucidated by mass and NMR spectroscopy. Vielanin D and E consist of bridged ring systems formally representing the Diels-Alder products from the hypothetical guaiane-type monomers. Due to a hemiketal function at C-8' both compounds occurred as epimeric mixtures.     

Four new immunomodulating steroidal glycosides from the stems of Stephanotis mucronata

Four new C-21 steroidal glycosides, mucronatosides E (1), F (2), G (3), and H (4), were isolated from the stems of Stephanotis mucronata. Two of them had the rare aglycone with a double bond between C-6 and C-7. Their structures were elucidated on the basis of spectroscopic data and chemical evidence. These isolated compounds were assayed for their immunological activities in vitro against concanavalin A (Con A)- and lipopolysaccharide (LPS)-induced proliferation of mice splenocytes. Compounds 2 and 4 showed immunosuppressive activities in a dose-dependent manner, while compounds 1 and 3 possessed immunoenhancing activities.     

海南大风子活性成分研究

用色谱技术对海南大风子(Hydnocarpus hainanensis (Merr.) Sleum.)枝条的乙醇提取物进行分离纯化,从中分离得到了6个化合物,经波谱数据分析与文献数据对照,分别鉴定为eoniferaldehyde (1)、mulberroside C(2)、mulberrofuran G(3)、mulb...     

Ancistrolikokine D,a 5,8'-coupled naphthylisoquinoline alkaloid,and related natural products from Ancistrocladus likoko

A new naphthylisoquinoline alkaloid, ancistrolikokine D, and the likewise 5,8'-coupled alkaloid ancistroealaine A, as well as two further, biosynthetically related, but nitrogen-free natural products, ancistronaphthoic acid B and cis-isoshinanolone, have been isolated from Ancistrocladus likoko J. LEACUTE;ONARD (Ancistrocladaceae). The 5,8'-coupling of the new alkaloids and of the alkaloids isolated earlier hints at a close phylogenetic relationship of A. likoko to other Central African Ancistrocladus species. The compounds show moderate activities against Leishmania donovani, Trypanosoma cruzi, and Trypanosoma brucei rhodesiense.     

New Karplus equations for 2JHH, 3JHH, 2JCH, 3JCH, 3JCOCH, 3JCSCH, and 3JCCCH in some aldohexopyranoside derivatives as determined using NMR spectroscopy and density functional theory calculations

The (1)H-(13)C coupling constants of methyl alpha- and beta-pyranosides of D-glucose and D-galactose have been measured by one-dimensional and two-dimensional (1)H-(13)C heteronuclear zero and double quantum, phase sensitive J-HMBC spectra to determine a complete set of coupling constants ((1)J(CH), (2)J(CH), (3)J(CH), (2)J(HH), and (3)J(HH)) within the exocyclic hydroxymethyl group (CH(2)OH) for each compound. In parallel with these experimental studies, structure, energy, and potential energy surfaces of the hydroxymethyl group for these compounds were determined employing quantum mechanical calculations at the B3LYP level using the 6-311++G( * *) basis set. Values of the vicinal coupling constants involving (1)H and (13)C in the C5-C6 (omega) and C6-O6 (theta) torsion angles in the aldohexopyranoside model compounds were calculated with water as the solvent using the PCM method. To test the relationship between (3)J(CXCH) (X=C, O, S) and torsion angle C1-X (phi) around the anomeric center, the conformations of 24 derivatives of glucose and galactose, which represent sequences of atoms at the anomeric center of C-glycosides (C-C bond), O-glycosides (C-O bond), thioglycosides (C-S bond), glycosylamines (C-N bond), and glycosyl halides (C-halogen (F/Cl) bond) have been calculated. Nonlinear regression analysis of the coupling constants (1)J(C1,H1), (2)J(C5,H6R), (2)J(C5,H6S), (2)J(C6,H5), (3)J(C4,H6R), (3)J(C4,H6S), (2)J(H6R,H5), and (3)J(H5,H6R) as well as (3)J(CXCH) (X=C, O, S) on the dihedral angles omega, theta, and phi have yielded new Karplus equations. Good agreement between calculated and experimentally measured coupling constants revealed that the DFT method was able to accurately predict J-couplings in aqueous solutions.     

Amurensiosides A-K, 11 new pregnane glycosides from the roots of Adonis amurensis

Five new pregnane tetraglycosides, amurensiosides A-E (1-5), two new pregnane hexaglycosides, amurensiosides F (6) and I (9), two new 18-norpregnane hexaglycosides, amurensiosides G (7) and H (8), and two new pregnane octaglycosides, amurensiosides J (10) and K (11), were isolated from the MeOH extract of the roots of Adonis amurensis. The structures of the new compounds were determined on the basis of extensive spectroscopic analysis, including two-dimensional (2D) NMR data, and the results of hydrolytic cleavage. The isolated compounds were evaluated for their cytotoxic activity against HSC-2 human oral squamous cell carcinoma cells.     

Steroidal glycosides from Cynanchum forrestii Schlechter

Nine new steroidal glycosides, cynaforrosides B, C, D, E, and F, based on a 13, 14: 14, 15-disecopregnane-type skeleton, cynaforrosides G, H, and I with a new aglycone named cynaforrogenin A, and cynaforroside J together with three known C21 steroidal glycosides cynatratoside A, hancoside and komaroside C were isolated from the ethanol extract of the roots of Cynanchum forrestii Schlechter. The structures of new compounds were determined on the basis of spectral and chemical evidence. Steroidal glycosides with three kinds of skeletons were isolated from this plant simultaneously. The sugar units of cynaforrosides B-I contained two moieties of glucoses and especially cynaforrosides E-I contained two glucoses with the mode of 1-->6 linkage, which were rare among steroidal glycosides of the genus Cynanchum.     

Compounds from Kadsura heteroclita and related anti-HIV activity

Phytochemical investigation of the stems of Kadsura heteroclita led to isolation of 16 compounds, including the triterpenoid named longipedlactone J (2), and two dibenzocyclooctadiene type lignans named heteroclitin I and J (3, 4). Compounds 8-10, 14, and 15 were weakly active as anti-HIV agents, whereas compounds 6 and 12 exhibited moderate anti-HIV activity with EC50 values of 1.6 microg/mL, and 1.4 microg/mL, therapeutic index (TI) values of 52.9, and 65.9, respectively. Their structures were established by spectroscopic methods, including application of 2D NMR techniques and CD spectra.     

Diversolides A-G, guaianolides from the roots of Ferula diversivittata

Seven sesquiterpene lactone derivatives, diversolides A-G (1-7), together with two known compounds, diversin (8) and stigmasterol, were isolated from the roots of Ferula diversivittata. The structures of these compounds were elucidated by extensive spectroscopic methods including 1D-(¹H and ¹³C) and 2D-NMR experiments (DQF-COSY, HSQC, HMBC, and NOESY) as well as high-resolution EIMS. Compounds 1, 4 and 6-8 were tested for their in vitro antifungal and antibacterial activities. Some of the tested compounds showed moderate antifungal and antibacterial activities with minimum inhibitory concentration (MIC) values from 40 to 80 μg/ml.     

A new kaempferol triglycoside from Fagonia taeckholmiana: cytotoxic activity of its extracts

In addition to apigenin, apigenin 7-O-glucoside, kaempferol 3-O-glucoside, kaempferol 3,7-di-O-rhamnoside, quercetin, and quercetin 3-O-glucoside, the methanolic extract of Fagonia taeckholmiana afforded a new compound identified as kaempferol 3-O-beta-l-arabinopyranosyl-(1-->4)-alpha-l-rhamnopyranoside-7-O-alpha-l-rhamnopyranoside. Identification of the isolated compounds was based on chemical and spectroscopic analyses including UV, FABMS, (1)H, (13)C and 2D NMR, and DEPT. The cytotoxic activities of the compounds against several cancer cell lines were determined.     

Ophiobolin E and 8-epi-ophiobolin J produced by Drechslera gigantea, a potential mycoherbicide of weedy grasses

Drechslera gigantea, a fungal pathogen isolated from large crabgrass (Digitaria sanguinalis) and proposed as a potential mycoherbicide of grass weeds, produces phytotoxic metabolites in liquid and solid cultures. Ophiobolin A and three minor ophiobolins i.e., 6-epi-ophiobolin A, 3-anhydro-6-epi-ophiobolin A and ophiobolin I were obtained from the liquid culture broths. Interestingly and unexpectedly, ophiobolins also appeared in cultures of this fungus and they were isolated together with the known ophiobolins B and J, and designed as ophiobolin E and 8-epi-ophiobolin J. They were characterized using essentially spectroscopic methods. It is noteworthy that D. gigantea produces such a plethora of bioactive organic substances. Some structure-activity relationship results are also discussed in this report.