Preparation and comparative properties of antisera against glyco-3 beta,12 alpha-dihydroxy-5-cholen-24-oic acid linked to bovine serum albumin at the C-3, C-15 alpha, and C-24 positions

Anti glyco-3 beta,12 alpha-dihydroxy-5-cholen-24-oic acid antisera were prepared by immunizing rabbits with hapten-bovine serum albumin (BSA) conjugates coupled at the C-3, C-15 alpha, and C-24 positions on the bile acid molecule, and their properties were investigated by heterologous combination assay using 125I-labeled tracer. The antiserum raised against the C-3 BSA conjugate showed poor titer and specificity, while the antisera from the other two conjugates showed satisfactorily high affinity constants (Ka = 5.0 x 10(8) and 7.0 x 10(8) M-1) and reasonable specificity, exhibiting negligible cross-reactivities with other major human bile acids and cholesterol. Among the unsaturated bile acids tested, high reactivity was observed with tauro-3 beta,12 alpha-dihydroxy-5-cholen-24-oic acid, which suggested that bridge phenomena were significant in this assay system.     

四环二萜的合成研究 5.对映贝壳杉-16-烯-19酸的合成

本文报道了一条从易得的甜叶菊苷出发经二次骨架重排合成了对映贝壳杉-16-烯-19-酸及其异构体.从甜叶菊苷合成对映贝壳杉-16-烯-19-酸的九步反应总产率为9%而合成对映贝壳杉-15-烯-19-酸的九步反应总产率炒17%.     

Determination of 3 beta,12 alpha-dihydroxy-5-cholen-24-oic acid and related bile acids in human serum by gas chromatography-mass spectrometry

The glycine, taurine and sulphate conjugates of 3 beta,12 alpha-dihydroxy-5-cholen-24-oic acid were synthesized as authentic samples for the analysis of this unusual bile acid. A highly sensitive and specific quantitative assay of the bile acid and related compounds has been developed by selected-ion monitoring in gas chromatography-mass spectrometry of their methyl ester-trimethylsilyl ether derivatives, using the deuterium labelled internal standards: [2H6]3 beta,12 alpha-dihydroxy-5-cholen-24-oic acid, [2H5]3 beta-hydroxy-5-cholen-24-oic acid, [2H7]cholic acid and their sulphates. Calibration curves for these bile acids were linear over the range 0.01-100 micrograms/ml in human serum. Recoveries of the bile acids and their conjugates ranged from 95 to 103% of the added amounts of their standard samples. The unsaturated bile acid was identified in a significant amount of 25.2 micrograms/ml in serum of an infant with liver disease, and its sulphate comprised 55.1% of the amount of the bile acid.     

High-performance functional ecopolymers based on flora and fauna

Liquid crystalline (LC) polymers of rigid monomers based on flora and fauna were prepared by in-bulk polymerization. Para-coumaric (p-coumaric) acid [4-hydroxycinnamic acid (4HCA)] and its derivatives were selected as phytomonomers and bile acids were selected as biomonomers. The 4HCA homopolymer showed a thermotropic LC phase only in a state of low molecular weight. The copolymers of 4HCA with bile acids such as lithocholic acid (LCA) and cholic acid (CA) showed excellent cell compatibilities but low molecular weights. However, P(4HCA-co-CA)s allowed LC spinning to create molecularly oriented biofibers, presumably due to the chain entanglement that occurs during in-bulk chain propagation into hyperbranching architecture. P[4HCA-co-3,4-dihydroxycinnamic acid (DHCA)]s showed high molecular weight, high mechanical strength, high Young's modulus, and high softening temperature, which may be achieved through the entanglement by in-bulk formation of hyperbranching, rigid structures. P(4HCA-co-DHCA)s showed a smooth hydrolysis, in-soil degradation, and photo-tunable hydrolysis. Thus, P(4HCA-co-DHCA)s might be applied as an environmentally degradable plastic with extremely high performance.     

High-performance liquid chromatographic separation of bile acids and bile alcohols diastereoisomeric at C-25

The high-performance liquid chromatographic separation of the 25R and 25S diastereoisomers of the bile alcohols 5 beta-cholestane-3 alpha,7 alpha,26-triol and 5 beta-cholestane-3 alpha,7 alpha, 12 alpha, 26-tetrol and the bile acids, 3 alpha,7 alpha-dihydroxy-5 beta-cholestane-26-oic acid and 3 alpha,7 alpha,12 alpha-trihydroxy-5 beta-cholestane-26-oic acid is described. A Radial-Pak microBondapak C18 reversed-phase cartridge was used for the separations and elutions were carried out with acetonitrile-water-methanol-acetic acid mixtures. All eight diastereoisomeric compounds showed baseline separation when up to 200 micrograms of the isomeric mixtures were injected into the column and the method can be used for isolation of pure diastereoisomers of these bile acids and bile alcohols.     

Synthesis of Novel C/D Ring Modified Bile Acids

Bile acid receptors have been identified as important targets for the development of new therapeutics to treat various metabolic and inflammatory diseases. The synthesis of new bile acid analogues can help elucidate structure–activity relationships and define compounds that activate these receptors selectively. Towards this, access to large quantities of a chenodeoxycholic acid derivative bearing a C-12 methyl and a C-13 to C-14 double bond provided an interesting scaffold to investigate the chemical manipulation of the C/D ring junction in bile acids. The reactivity of this alkene substrate with various zinc carbenoid species showed that those generated using the Furukawa methodology achieved selective α-cyclopropanation, whereas those generated using the Shi methodology reacted in an unexpected manner giving rise to a rearranged skeleton whereby the C ring has undergone contraction to form a novel spiro–furan ring system. Further derivatization of the cyclopropanated steroid included O-7 oxidation and epimerization to afford new bile acid derivatives for biological evaluation.     

N-丙烯酰-2-氯吩噻嗪、N-丙烯酰-2-乙酰基吩噻嗪单体和聚合物的合成以及荧光行为的研究

含芳杂环的丙烯酰类功能性单体及其聚合物的合成一直吸引人们的兴趣,原因之一是由于这类单体可用一般的自由基引发剂引发聚合,这类聚合物所表现出的光化学、电化学性质甚被瞩目。如含吩噻嗪的丙烯酰类衍生物可以和缺电子的化合物形成电荷转移     

Synthesis of 6-hydroxylated bile acids and identification of 3 alpha,6 alpha,7 alpha,12 alpha-tetrahydroxy-5 beta-cholan-24-oic acid in human meconium and neonatal urine

Three 6-hydroxylated bile acids, 3 alpha,6 alpha,7 alpha,12 alpha-, 3 alpha,6 beta,7 alpha,12 alpha- and 3 alpha,6 beta,7 beta,12 alpha-tetrahydroxy-5 beta-cholan-24-oic acids, were synthesized from methyl cholate, and a sensitive method was developed for analyzing them by gas chromatography-mass spectrometry for the stoichiometric study of fetal bile acids. 3 alpha,6 alpha,7 alpha,12 alpha-Tetrahydroxy-5 beta-cholan-24-oic acid (6 alpha-hydroxylated cholic acid) was identified from human meconium and healthy neonatal urine by comparison with the mass spectrum of the reference compound. In human meconium, 6 alpha-hydroxylated cholic and chenodeoxycholic acids were determined in 1.2% and 29.0% of the total bile acids, respectively. We discuss the significance of hydroxylation at the C-1 beta and C-6 alpha positions of bile acids and their elimination in fetal and neonatal periods.     

N-丙烯酰-2-氯吩噻嗪、N-丙烯酰-2-乙酰基吩噻嗪单体和聚合物的合成以及荧光行为的研究

Two N-acrylic monomers having phenothiazine moieties , N-acrylyl-2-chlorophe-nothiazine ( I ) , N-acrylyl-2-acetylphenothiazine ( I ) were synthesized and their polymers were obtained by free radical polymerization . The fluorescence study showed that at the same molar concentration of the chromophores, the fluorescence intensities of the polymers were much stronger than that of the monomers. This would be explained by what we called "Structural Self-quenching Effect. " The Stern-Volmer constants of the polmers quenched by several electron defecient vinyl monomers were obtained. The results indicated that their quenching efficiencies were relevant to the degree of the electron deficiency of the double bond.     

Nucleus-fluorinated aromatic polyethers

Methods of synthesis, the structure, properties, and application areas of nucleus-fluorinated aromatic polyethers are considered. The main attention is given to polymers for which chain propagation occurs via formation of an ether bond, and the fluorinated monomers suitable for the synthesis of these polymers are indicated. Approaches to the incorporation of sulfonic acid, phosphoric acid, aldehyde, and maleimide groups and other reactive moieties into fluorinated aromatic polyethers are analyzed.     

Synthesis of 5 beta-cholestane-3 alpha,6 beta,7 alpha,25,26-pentol and identification of a novel bile alcohol, alpha-trichechol, present in the West Indian manatee bile

In order to confirm the structure of alpha-trichechol, the major bile alcohol of the West Indian manatee, chemical synthesis of 5 beta-cholestane-3 alpha,6 beta,7 alpha,25,26-pentol was carried out. The chain of 3 alpha-hydroxy-5 beta-chol-6-en-24-oic acid was elongated by an Arndt-Eistert reaction to form 3 alpha-hydroxy-26,27-dinor-5 beta-cholest-6-en-25-oic acid. The unsaturated C25 bile acid was converted into 3 alpha,6 beta,7 alpha-trihydroxy-25-homo-5 beta-cholan-25-oic acid by 1,2-glycol formation of the delta 6-double bond. The acetylated derivative of the trihydroxy C25 bile acid was then converted into 3 alpha,6 beta,7 alpha,26-tetraacetoxy-27-nor-5 beta-cholestan-25-one by successive treatment with thionyl chloride, diazomethane, and acetic acid. A Grignard reaction of the 25-oxo compound with methylmagnesium iodide afforded the desired bile alcohol, 5 beta-cholestane-3 alpha,6 beta,7 alpha,25,26-pentol. By direct comparison with the synthetic pentahydroxy bile alcohol, the structure of the naturally occurring alpha-trichechol was determined to be 5 beta-cholestane-3 alpha,6 beta,7 alpha,25,26-pentol.     

Vinyl monomers bearing chromophore moieties and their polymers. III. Synthesis and photochemical behavior of acrylic monomers having phenothiazine moieties and their polymers

Four acrylic monomers bearing phenothiazine moieties, i.e., N-acrylyl-phenothiazine (APT), N-acrylyl-2-chlorophenothiazine (ACPT), N-acrylyl-2-acetylphenothiazine (AAPT), and 10-acrylyl-1-azaphenothiazine (AAzPT) were synthesized by dehydrohalogenation of the corresponding N-(β-chloropropionyl)-substituted phenothiazine derivatives with 1,8-diazabicyclo[5.4.0]undec-5-ene (DBU). These monomers could easily be polymerized by initiation with AIBN. The emission fluorescence spectra of the monomers and their polymers were recorded, which showed that the polymers displayed much stronger fluorescence than their corresponding monomers at the same chromophore concentrations. This phenomenon, as termed as “structural self-quenching effect,” was commonly observed for acrylic monomers bearing chromophore moieties and ascribed to the coexistence of the electron-donating chromophore and the electron-accepting double bond in the same molecule. Because of the formation of exciplex, the monomer APT, as well as ACPT, AAPT, AAzPT, and their polymers, could initiate the photopolymerization of AN. The charge transfer phenomenon between P(APT), P(ACPT), and C₆₀ was also explored. © 1996 John Wiley & Sons, Inc.     

含荧光生色基团烯类单体及其聚合物的光化学行为

近年来关于电荷转移现象的研究因理论及应用方面的重要性而备受瞩目。缺电子性丙烯酰类单体可以和给电子性化合物形成激态电葆转移复合物进而引发光聚合。我们合成了一系列同一分子中既含有给电子性荧光生色团又含缺电子性双键的烯类单体,发现这类单体在相同生色团浓度下的荧光强度均无穷氏人相应的聚合物的荧光强度。我们将这咎现象称为荧光结构自猝灭效应（ＳＳＱＥ）,以区别于众所周知的浓度自猝灭现象。对于电子状态与之相反的     

含胆汁酸和胆固醇的双亲性聚合物的研究进展

胆固醇和胆汁酸是广泛存在于自然界中的天然物质 ,生物相容性好 ,被广泛地用于高分子的疏水性改性 ,得到的双亲性聚合物 ,在水相中可以自组装或自聚集成纳米粒子。本文综述了含胆固醇或胆汁酸的双亲性聚合物的最新研究进展以及它们在药物载体系统中的应用。     

A new steroid aromatization rearrangement involving inversion of sidechain configuration

The bile acid, cholic acid, has been transformed into 3α-hydroxy-12-methyl-18-nor-5β, 17α-chola-8,11,13-trien-24-oic acid. The constitution of this novel type of steroid (benzenoid C-ring with 17α-sidechain) has been supported by chemical degradation, and confirmed by crystal structure analysis of the methyl ester iodoacetate derivative.     

Novel synthesis of photocrosslinkable polymers

A new preparative route to photocrosslinkable polymers in which the polymers are produced directly from the polymerization of vinyl monomers having photocrosslinkable groups has been investigated. The photosensitive resins thus produced have higher sensitivity and resolution than conventional photosensitive resins. The monomers were synthesized from the esterification of vinylphenols or vinyl β-chloroethyl ether with cinnamic acid, β-styrylacrylic acid, and their homologs, and from the etherification of vinyl β-chloroethyl ether with hydroxychalcones. Homopolymerizations of these monomers and their copolymerizations with other comonomers were investigated with the use of both radical and ionic initiators. It is shown that radical polymerization of the monomers gave soluble polymers only at low conversion. Anionic initiators did not initiate polymerization. Cationic polymerization imparted soluble polymers in high yield, except for the monomers bearing cyano groups, which generally gave insoluble polymers. Infrared and NMR spectroscopic investigation of the cationically obtained soluble polymers and comparative investigation by cationic polymerization of model compounds indicated that polymerization of the monomers proceeds through the vinyl double bond without affecting the photosensitive unsaturated bond. Thus, linear photocrosslinkable polymers with an intact photoreactive group may be produced by cationic polymerization. In general, these polymers have uniform structure and modifiable physical properties depending on the monomer used. The polymer thus obtained from β-vinyloxyethyl cinnamate has been shown to have excellent properties for use as a photo-resist.     

Synthesis and properties of reactive liquid crystal monomers and side-chain liquid crystalline polymers

Two nematic liquid crystal (LC) monomers containing double bonds in the side chain were designed and synthesised. Length of the side groups varied from 1 to 2 methylene units. The side-chain polymers were synthesised by hydrosilylation reaction. The molecular structures of the intermediates and the LC monomers were characterised by Fourier transform infrared, elemental analysis and nuclear magnetic resonance spectroscopy. The thermal phase behaviour of the monomers and polymers were investigated by differential scanning calorimetry and polar optical microscopy coupled with hot stage. The LC monomers showed only one nematic mesophase in the cooling process. And, the two polymers exhibit an enantiotroppic nematic mesophase either in the heating or in the cooling process.     

Design and Synthesis of New Bile AcidSterol Conjugates Linked via 1,2,3‐Triazole Ring

A new steroid conjugates have been obtained from bile acids and sterol derivatives using ‘click chemistry’. Intermolecular 1,3‐dipolar cycloaddition of the propargyl ester of bile acids (lithocholic, deoxycholic, and cholic acid) and azide derivatives of sterols (ergosterol and cholesterol) gave a new bile acid? sterol conjugates linked with a 1,2,3‐triazole ring. The structures of all products were confirmed by spectroscopic (¹H‐ and ¹³C‐NMR, and FT‐IR) analyses, mass spectrometry (ESI‐MS), and in silico biological activity evaluation methods (PASS), as well as PM5 semiempirical methods.     

Analysis of Polyunsaturated Fatty Acids Using High Performance Liquid Chromatography – Atmospheric Pressure Chemical Ionization Mass Spectrometry

Analysis of polyunsaturated fatty acids using high performance liquid chromatography–atmospheric pressure chemical ionization mass spectrometry is described. The standard fatty acid methyl esters from 16 to 22 carbons were analyzed by LC‐MS with APCI. The effect of orifice voltage and total carbon atoms versus number of double bonds in each homologue on the mass spectra is discussed. The correction coefficients for homologues from saturated fatty acids to hexaenoic acid are also mentioned.     

Steroid Cyclophanes as Artificial Cell-surface Receptors. Molecular Recognition and its Consequence in Signal Transduction Behavior

Steroid cyclophanes, bearing four bile acid moieties covalently placed on a tetraazaparacyclophane skeleton, were designed and synthesized as artificial cell-surface receptors. Guest-binding behavior of the steroid cyclophanes embedded in a bilayer membrane formed with a synthetic peptide lipid was clarified by means of fluorescence and circular dichroism spectroscopy. We found that the steroid cyclophane effectively bound aromatic guests in both bilayer membranes and aqueous solution. In addition, copper(II) ions acted as a guest species for the steroid cyclophane and a competitive inhibitor toward a NADH-dependent lactate dehydrogenase (LDH). On these grounds, we constituted a supramolecular assembly as an artificial signaling system in combination with the steroid cyclophane, a cationic peptide lipid, and LDH. As a consequence, the steroid cyclophane acted as an effective artificial cell-surface receptor being capable of transmitting an external signal to the enzyme in collaboration with copper(II) ions as a signal transmitter.