Utility of isolated hepatocytes and radio-HPLC-MSn for the analysis of the metabolic fate of 19-nortestosterone laurate in cattle.

The metabolic fate of 19-nortestosterone laurate in cattle was investigated to evaluate target analyte(s) appropriate to surveillance for illicit use as a growth promoting agent. Bovine hepatocytes were incubated with either [3H]19-nortestosterone laurate (19-NTL; 4-estren-17 beta-laurate-3-one) or [3H]19-nortestosterone (19-NT; 4-estren-17 beta-ol-3-one; nandrolone). Hepatocyte medium was extracted with solid phase C18 media and analysed by narrow bore radio-HPLC-MSn (LCQ, Finnigan) to evaluate the structure of metabolites of 19-NTL and 19-NT. Radio-HPLC of hepatocyte medium extracts following incubation with [3H]19-NTL confirmed that the first step of biotransformation in liver was hydrolysis of the fatty acid ester to release [3H]19-NT, which, in turn, was converted into a range of metabolites of diverse polarity. Hydrolysis of hepatocyte medium extracts with beta-glucuronidase (Helix pomatia) indicated that some of these metabolites were glucuronide or sulfate conjugates. Structural analysis of unconjugated metabolities by positive-ion atmospheric pressure chemical ionisation MS2 and comparison with available reference preparations indicated biotransformation of 19-NT to 4-estren-17 alpha-ol-3-one, 4-estren-3, 17-dione (major metabolite after 1 h), n-hydroxy-4-estren-3, 17-dione, n-hydroxy-4-estren-17-ol-3-one, 5 beta-estran-3 alpha-ol-17-one (noretiocholanolone) and 5 beta-estran-3 alpha, 17 beta-ol (major metabolite after 4 h). Conjugated metabolites were analysed by electrospray ionization, which revealed the presence of glucuronide conjugates of alpha-(trace) and beta-epimers of 19-NT, n-hydroxy-4-estren-3, 17-dione, n-hydroxy-4-estren-17-ol-3-one and 5 beta-estran-3 alpha, 17 beta-diol. These studies provide a clear indication of the route of hepatic metabolism in the bovine, which may now be readily substantiated by reference to samples, such as urine or bile, derived from animals treated with unlabelled 19-NTL.     

Two new 19-oxygenated polyhydroxy steroids from the hainan soft coral Sinularia sp

Two new 19-oxygenated polyhydroxy steroids, 24-methylcholesta-5, 24(28)-diene-3 beta, 7 beta, 19-triol-19-monoacetate (1), 24-methylcholesta-5, 24(28)-diene-3 beta, 7 beta, 19-triol-7 beta, 19-diacetate (3), together with a known steroid, 24-methylcholesta-5, 24(28)-diene-3 beta, 7 beta, 19-triol-7 beta-monoacetate (4), have been isolated from the soft coral Sinularia sp. collected from the South China Sea and characterized through interpretation of spectral data.     

Stereochemistry of NaBH4 reduction of a 19-carbonyl group of 3-deoxy androgens. Synthesis of [19S-3H]- and [19R-3H]-labeled aromatase inhibitors having a 19-hydroxy group

To study the stereochemical aspects of the aromatase reaction of androst-4-en-17-one (1) and its 5-ene isomer 4, competitive inhibitors of aromatase, the [19S-(3)H]- and [19R-(3)H]-labeled 19-hydroxy derivatives 2 and 5, were synthesized through NaB(3)H(4) reduction of the corresponding 19-aldehydes 3 and 6 as a key reaction. The hitherto unknown stereochemistry of the NaB(3)H(4) reduction was established based on the deuterium-labeling experiments with NaB(2)H(4). A comparison of (1)H-NMR spectra of the NaB(2)H(4) reduction products of 19-als 3 and 6 with those of the respective authentic steroids revealed that the ratios of 19S-(2)H to 19R-(2)H were 90 : 10 for the 4-ene steroid 2 and 70 : 30 for the 5-ene isomer 5, respectively. Jones oxidation of the [19S-(2)H]19-ols, followed by the non-labeled NaBH(4) reduction, gave the corresponding [19R-(2)H]19-ols 2 and 5 (R-(2)H : S-(2)H=90 : 10 for steroid 2 and 70 : 30 for steroid 5). The stereoselectively (3)H-labeled compounds 2 and 5 were similarly obtained in these sequences.     

Diterpenoide Chinomethane,vinyloge Chinone und ein Phyllocladan-Derivat aus Plectranthus purpuratus HARV. (Labiatae)

Diterpenoids from Leaf Glands of Plectranthus purpuratus: p-Quinomethanes, Extended Quinones, p-Acylcatechols and a Novel Phyllocladanon Derivative From the complex mixture of terpenoids from the title plant, the following novel diterpenoids have been isolated: 11-hydroxy-19-(3-methyl-2-butenoyloxy)- and 11-hydroxy-19-(3-methylbutanoyloxy)-5,7,9 (11), 13-abietatetraen-12-one ( 1a / 1b ), 11-hydroxy-19-(3-methyl-2-butenoyloxy)- and 11-hydroxy-19-(3-methylbutanoyl-oxy)-7,9(11), 13-abietatrien-6,12-dione ( 2a / 2b ), 6α, 11-dihydroxy-19-(3-methyl-2-butenoyloxy)- and 6α, 11 -dihydroxy-19-(3-methylbutanoyloxy)-7,9 (11), 13-abieta-trien-12-one ( 3a / 3b ), 11,12-dihydroxy-19-(3-methyl-2-butenoyloxy)- and 11,12-di-hydroxy-19-(3-methylbutanoyloxy)-8,11,13-abietatrien-7-one ( 4a / 4b ), and (16R)-17,19-diacetoxy-16-hydroxy-13β-kauran-3-one (=(16R)-17,19-diacetoxy-16-hydro-xyphyllocladan-3-one; 10 ). Compounds 2 and 3 are derivates of taxodione and taxodone, respectively, 4 is a derivative of cryptojaponol. The structure of 10 is Wised on a single-crystal- X -ray analysis and CD . data.     

Involvement of DPY19L3 in Myogenic Differentiation of C2C12 Myoblasts

DPY19L3 has been identified as a C-mannosyltransferase for thrombospondin type-1 repeat domain-containing proteins. In this study, we focused on the role of DPY19L3 in the myogenic differentiation of C2C12 mouse myoblast cells. We carried out DPY19L3 gene depletion using the CRISPR/Cas9 system. The result showed that these DPY19L3-knockout cells could not be induced for differentiation. Moreover, the phosphorylation levels of MEK/ERK and p70S6K were suppressed in the DPY19L3-knockout cells compared with that of parent cells, suggesting that the protein(s) that is(are) DPY19L3-mediated C-mannosylated and regulate(s) MEK/ERK or p70S6K signaling is(are) required for the differentiation.     

Paramagnetic relaxation-based 19f MRI probe to detect protease activity

A novel design principle for 19F MRI probes detecting protease activity was developed. This principle is based on 19F MRI signal quenching by the intramolecular paramagnetic effect from Gd3+. The intramolecular Gd3+ dramatically attenuated the 19F probe signal, and the paramagnetic effect was cancelled by the probe hydrolyzation by caspase-3. Using this probe, it was shown that the probe could detect caspase-3 activity spatially from a phantom image using 19F MRI.     

Steroids and sex hormons. Part 264. Lewis acid catalyzed reversible [1,5]-hydride shift in 3,19-epoxy-steroids

3β, 19-Epoxy-3 α-methoxy-steroids (e.g. 1 , Scheme 1) are converted into the corresponding 3 α-methoxy-19-oxo compounds (e.g. 3 ) in the presence of boron trifluoride etherate, via an intramolecular hydride ion transfer from C (19) to (3) which is shown to be an equilibrium process. By subjecting the specifically deuteriated (19 S)- and (19 R)-compounds 1b and 1c to this reaction it was shown to be highly stereoselective.     

19-nor-11-Oxooleanan-12-ene and 18,19-seco-19-oxours-11,13(18)-diene triterpenes from Diospyros decandra bark

Four new triterpenes, 2α,3β-dihydroxy-19-nor-11-oxo-20-dimethylurs-12-en-24,28-dioic acid (equivalent to 2α,3β-dihydroxy-19-nor-11-oxoolean-12-en-24,28-dioic acid), 2α,3β-dihydroxy-18,19-seco-19-oxours-11,13(18)-dien-24,28-dioic acid, 2α,3β,19α-trihydroxy-11-oxours-12-en-24,28-dioic acid and 2α,3β,19α-trihydroxy-28-1′-β-d-[glucopyranosyl-(1″→6′)-glucopyranosyl]-urs-12-en-24,28-dioic acid were isolated from the methanol extract of the bark of Diospyros decandra as their acetate-methyl ester derivatives. The first two compounds represent the biosynthetic transformation products of 2α,3β,19-trihydroxyurs-24,28-dioic acid via oxidative rearrangement of ring E.     

Cucurbitane‐type triterpene glycosides from the fruits of Momordica charantia

The chemical study of Momordica charantia fruits led to the isolation of three new cucurbitane triterpene glycosides, momordicosides U, V, and W (1–3). The structures of these compounds were determined to be (19R, 23R)‐5β, 19‐epoxy‐19‐methoxycucurbita‐6,24‐diene‐3β, 23‐diol 3‐O‐β‐D‐allopyranoside (1), (23R)‐5β, 19‐epoxycucurbita‐6,24‐diene‐3β, 23‐diol 3‐O‐β‐D‐allopyranoside (2), and (19R)‐5β, 19‐epoxy‐19,25‐dihydroxycucurbita‐6,23(E)‐diene‐3β‐ol 3‐O‐β‐D‐glucopyranoside (3), by chemical and spectroscopic methods. Copyright © 2010 John Wiley & Sons, Ltd.     

Cucurbitane triterpenoids from Momordica charantia

Three new cucurbitane-type triterpenoid saponins, 23-O-beta-D-allopyranosyl-5beta,19-epoxycucurbita-6,24-diene-3beta,22(S),23(S)-triol-3-O-beta-D-glucopyranoside (1), 23-O-beta-D-allopyranosyl-5beta,19-epoxycucurbita-6,24-diene-3beta,22(S),23(S)-triol-3-O-beta-D-allopyranoside (2), and 23-O-beta-D-allopyranosyl-5beta,19-epoxycucurbita-6,24-diene-3beta,19(R), 22(S),23(S)-tetraol-3-O-beta-D-allopyranoside (3), named momordicoside M, N, and O, respectively, along with one known saponin momordicoside L (4), were isolated from the fresh fruits of Momordica charantia. The structures of these saponins were elucidated on the basis of chemical properties and spectral data.     

19-electron intermediates and cage-effects in the photochemical disproportionation of [CpW(CO)3]2 with Lewis bases

The role of 19-electron intermediates in the photochemical disproportionation of [CpW(CO)3]2 (Cp = C5H5) with Lewis bases (PR3; R = OMe, Bu, Ph) is investigated on the ultrafast time scale using femtosecond VIS-pump, IR-probe spectroscopy. Formation of a 19-electron (19e) species CpW(CO)3PR3*by coordination of PR3 with photogenerated 17-electron (17e) radicals CpW(CO)3* is directly observed, and equilibrium is established between the 17e radicals and the 19e intermediates favoring 19e intermediates in the order: Bu > OMe > Ph. Steric effects dominate the 17e/19e equilibrium when the cone-angle of the Lewis base exceeds a certain limiting value (between 132 degrees and 145 degrees ), but below this value electronic properties of the Lewis base control the 17e/19e dynamics. Disproportionation occurs in less than 200 picoseconds by electron transfer between a solvent caged 17e radical and 19e, highly reducing species. The rate and extent of ultrafast disproportionation depends on both the identity and concentration of the Lewis base. In low concentrations of PR3 (typically 1-2 M or less) or with Lewis bases whose equilibrium heavily favors 17e radicals (e.g., PPh3), disproportionation is rate-limited by breakdown of the solvent cage. Density functional theory calculations on vibrational frequencies and charge distributions of the various complexes support the experimental results.     

Studies on the reaction of p-acid fuchsin with auric chloride and palladous chloride

The constitution of the molecular compound 3PdCl2(2C19H17N3.HCl), formed by a new selective and sensitive palladium-test, has been investigated and a coordination formula proposed. Analogous compounds formed by gold and para fuchsin were isolated and found to have molecular formulae of 3AuCl3(C19H17N4.HCl) and 2AuCl3(C19H17N3.HCl). There exists also a mixed gold-palladium-fuchsin compound 4AuCl3 2(C19H17N3.HCl).PdCl2 for which a coordination formula is given. The new compounds can be considered as bi-nuclear polylinked chelate rings. They correspond to benzidine complex-compounds, found by spacu, for which a reasonable binuclear formula is proposed.     

Pd-catalyzed synthesis of 2-alkynyl derivatives of 19β,28-epoxy-18α-olean-1-en-3-one

Basing on Sonogashira reaction of 2-iodo-19β,28-epoxy-18α-olean-1-en-3-one with alkynes an effective approach was developed to the synthesis of 2-alkynyl derivatives of 19β,28-epoxy-18α-olean-1-en-3-one. Initial 2-iodo-19β,28-epoxy-18α-olean-1-en-3-one was obtained by isomerization of the accessible betulin into allobetulin in the presence of Amberlyst 15, oxidation of allobetulin to 19β,28-epoxy-18α-olean-1-en-3-one under the action of 2-iodoxybenzoic acid, and iodination of the obtained enone in the presence of DMAP.     

Synthesis of New Heterocyclic Compounds Using 2‐(3,3‐dimethyl‐1H‐pyrroloisoquinolin‐2(3H)‐ylidene)malonaldehydes

Isoquinolin‐5‐ylhydrazinium chloride 13 and 5‐bromoisoquinolin‐8‐ylhydrazinium chloride 14 were converted via Fischer syntheses with 3‐methylbutan‐2‐one into indolenines, 2,3,3‐trimethyl‐3H‐pyrrolo[2,3‐f]isoquinoline 15 and 5‐bromo‐2,3,3‐trimethyl‐3H‐pyrrolo[3,2‐h]isoquinoline 16 , respectively. Exposure of the indolenines to the Vilsmeier reagent produced diformyl compounds 17 and 18 , which reacted with arylhydrazines to give the corresponding pyrazoles 19a , 19b , 19c , 19d , 19e , 19f , 19g , 19h , 19i and 20a , 20b , 20c , 20d , 20e , 20f , 20g . Reaction of 17 with thiourea gave a pyrimidine‐2(1H)‐thione 23 or with hydroxylamine hydrochloride, an isoxazole 24 .     

Comparison of the Sol-gel Method with the Coprecipitation Technique for Preparation of Hexagonal Barium Ferrite

Hexagonal barium ferrite BaFe12O19 particles were prepared by sol-gel and coprecipitation methods, respectively. The composition of the so-obtained materials was investigated by means of XRD. By the sol-gel method, non-anticipated intermediate crystalline phases, such as γ-Fe2O3, α-Fe2O3, BaCO3, and BaFe2O4 etc., were formed with the delay of the formation of BaFe12O19. The formation of single phase BaFe12O19 required calcination at 850 oC for 4 h. On the other hand, using coprecipitation technique, amorphous hydroxide precursor was directly transferred into BaFe12O19 almost without the formation of intermediate crystalline phases. BaFe12O19 was prepared by calcining at 700 oC for 3 h. The results were confirmed by ESEM and VSM analyses. Based on the already reported results and the observed results in this study, it can be concluded that the coprecipitaion technique is easier to control than the sol-gel method for preparation of BaFe12O19 at a low temperature.     

New ent-kaurane diterpenes with chiral epoxyangelate moieties from Wedelia prostrata

Four new ent-kaurane diterpenes with chiral epoxyangelate moieties, (2′R,3′R)-3 a- (2′,3′-epoxyangeloyloxy)-kaur-16-en-19-oic acid (1), (2′S,3′S)-3 a- (2′,3′-epoxyangeloyloxy)-kaur-16-en-19-oic acid (2), (2′S,3′R)-3 a- (2',3'-epoxyangeloyloxy)-kaur-16-en-19-oic acid (3) and (2′R,3′S)-3α- (2′,3'-epoxyangeloyloxy)-kaur-16-en-19-oic acid (4), along with eight known diterpenes (5-12), were isolated from Wedelia prostrata. The absolute configurations of the new structures were determined by X-ray crystallography,ECD calculations and chemical methods. All compounds were evaluated for their cytotoxicity activities on human HepG-2 cells,with IC_(50) values of 11.72 ±0.22 μmol/L to 54.75±1.12 μmol/L.     

Synthesis of (s)-1-{3-[4-(4-benzo[d]isothiazol-3-yl-piperazin-1-yl)-3-fluoro-phenyl]-2-oxo-oxazolidin-5-ylmetyl}-3-substituted-urea derivatives as antibacterial agents

A new series of (s)-1-{3-[4-(4-benzo[d]isothiazol-3-yl-piperazin-1-yl)-3-fluoro-phenyl]-2-oxo-oxazolidin-5-ylmetyl}-3-substituted-urea derivatives have been synthesized and characterized with spectral data, such as IR, NMR and Mass spectroscopies. All compounds are in vitro evaluated for their efficacy as antimicrobial agent against the gram-positive pathogenic strains such as Bacillus subtilis ATCC 6633, Staphylococcus aureus ATCC 25923, Staphylococcus epidermidis ATCC 12228 and Streptococcus pyogens ATCC 8668. Five compounds ( 19k , 19l , 19m , 19n and 19o ) out of 15 compounds showed moderate activity.     

形貌可控纳米SrFe_(12)O_(19)的制备及其磁性能

以FeCl3为原料,NaOH作为沉淀剂,通过化学沉淀法,制备出球状的Fe(OH)3中间体,同时以FeCl2为原料,采用化学沉淀法,分别使用NH3·H2O、Na2CO3和NaOH作为沉淀剂制得了不同形貌的中间体,利用柠檬酸法在中间体表面包裹锶的柠檬酸络合物,煅烧后分别制得了球形、纺锤体及棒状的纳米SrFe12O19.利用X射线衍射(XRD)和透射电镜(TEM)等测试手段对不同形貌的纳米SrFe12O19进行表征,并利用振动样品磁强计(VSM)对磁性能进行研究.结果表明:在用化学沉淀-柠檬酸法制备SrFe12O19的过程中,铁盐的种类以及沉淀剂的碱性对中间体的物相和SrFe12O19的形貌有着至关重要的影响.当原料为Fe3+时,制得了球形的纳米SrFe12O19;当原料为Fe2+时,利用碱性不同的沉淀剂可制得不同形貌的纳米SrFe12O19.随着沉淀剂碱性的增加,所得SrFe12O19的长径比增加,形貌各向异性增加.SrFe12O19的矫顽力(Hc)主要取决于粒子的各向异性,各向异性越大,矫顽力越大,饱和磁化强度(Ms)随着样品的各向异性的增加也有所增加,以FeCl2为原料,NaOH作为沉淀剂时制得的棒状SrFe12O19的矫顽力和饱和磁化强度最大分别为458.2kA·m-1和64.2A·m2·kg-1.     

Structure resolution of Ba5Al3F19 and investigation of fluorine ion dynamics by synchrotron powder diffraction, variable-temperature solid-state NMR, and quantum computations

The room temperature structure of Ba(5)Al(3)F(19) has been solved using electron microscopy and synchrotron powder diffraction data. One-dimensional (1D) (27)Al and ultrafast magic-angle-spinning (MAS) (19)F NMR spectra have been recorded and are in agreement with the proposed structural model for Ba(5)Al(3)F(19). The (19)F isotropic chemical shift and (27)Al quadrupolar parameters have been calculated using the CASTEP code from the experimental and density functional theory geometry-optimized structures. After optimization, the calculated NMR parameters of both the (19)F and (27)Al nuclei show improved consistency with the experimental values, demonstrating that the geometry optimization step is necessary to obtain more accurate and reliable structural data. This also enables a complete and unambiguous assignment of the (19)F MAS NMR spectrum of Ba(5)Al(3)F(19). Variable-temperature 1D MAS (19)F NMR experiments have been carried out, showing the occurrence of fluorine ion mobility. Complementary insights were obtained from both two-dimensional (2D) exchange and 2D double-quantum dipolar recoupling NMR experiments, and a detailed analysis of the anionic motion in Ba(5)Al(3)F(19) is proposed, including the distinction between reorientational processes and chemical exchange involving bond breaking and re-formation.     

增强CT联合血清指标诊断结直肠癌的价值

本文探讨癌胚抗原(CEA)、糖类抗原19-9(CA19-9)、胰岛素样生长因子结合蛋白-3(IGFBP-3)及增强CT在结直肠癌中的联合诊断效果。选取100例结直肠癌患作为观察组,同时选取结直肠良性肿瘤患者60例作为对照组,检测血清CEA、CA19-9、IGFBP-3,同时给予增强CT检查。观察组血清CEA和CA19-9高于对照组(P<0.05),而IGFBP-3低于对照组(P<0.05);TNM分期Ⅲ~Ⅳ和Ⅰ~Ⅱ患者血清CEA、CA19-9和IGFBP-3差异比较有统计学意义(P<0.05);增强CT联合血清指标联合诊断灵敏性为89.00%、特异性为90.00%;增强CT诊断结直肠癌T分期、N分期与病理结果Kappa值分别为0.696和0.790(P<0.05)。CEA、CA19-9、IGFBP-3联合增强CT是一种具有较高效能的结直肠癌诊断方法。