胆酸酯及其甲基丙烯酸衍生物的制备

以HCl为催化剂,合成了脂肪族二元醇单胆酸酯(2~5)。运用甲基丙烯酰氯和甲基丙烯酸酐作酰化试剂,三乙胺作缚酸剂,4-(二甲氨基)吡啶作催化剂,合成了分子中含有不同数量甲基丙酰基的胆酸衍生物(6~9)。实验结果表明,当用甲基丙烯酰氯作酰化剂时,2~5分子中羟基的反应活性顺序是:CH2-OH>3-OH>12-OH>7-OH。     

胆酸甲酯(甲基)丙烯酰基衍生物的合成

以(甲基)丙烯酰氯为酰化剂,三乙胺做缚酸剂合成了分子中含有1~3个(甲基)丙烯酰基的胆酸衍生物。结果显示,以酰氯作酰化试剂,胆酸甲酯分子中3个羟基的反应活性顺序是:C3-OH>C12-OH>C7-OH。     

2-取代-3,4-二氢-1-异喹啉酮的合成及其血管舒张活性

以3-羟基-4,5-亚甲二氧基苯甲酸甲酯或5-羟基-1,3-苯二甲酸二甲酯为原料,经烯丙基醚化、Claisen重排、氧化、与伯胺反应(生成Schiff碱)、还原、分子内酯的酰化合成了4种新的2-取代-3,4-二氢-1-异喹啉酮(1a～1d),其结构经1HNMR和MS表征。离体动脉环张力实验证明1在浓度为1×10-4mol.L-1时具有明显舒张血管的作用。     

3-羟基异恶唑的O-和N-酰化及其区域选择性研究 Ⅱ.3-羟基-5-甲基异恶唑O-和N-酰化产物的选择性合成

本文研究了不同反应条件下3-羟基-5-甲基异恶唑(1)与3-甲基-2- 对氯苯基丁酰氯(2a)的反应,提出了区域选择性合成O-和N-酰化产物的方法.在三乙胺存在下,乙腈为溶剂,1和2a～2e反应得到含量为88～96%的O-酰化产物3a～3e,而若将1 转化为相应的异恶唑硅醚4,再与2a～2i反应,则得到含量为86～97%的N-酰化产物5a～5i.试验表明,在DMAP催化下,3a和5a可发生O-/N-酰基转移反应     

3-羟基异噁唑的O-和N-酰化及其区域选择性研究 Ⅱ.3-羟基-5-甲基异噁唑O-和N-酰化产物的选择性合成

本文研究了不同反应条件下3-羟基-5-甲基异噁唑(1)与3-甲基-2-对氯苯基丁酰氯(2a)的反应,提出了区域选择性合成O-和N-酰化产物的方法。在三乙胺存在下,乙腈为溶剂,1和2a～2e反应得到含量为88～96％的O-酰化产物3a～3e;而若将1转化为相应的异噁唑硅醚4,再与2a～2i反应,则得到含量为86～97％的N-酰化产物5a～5i。试验表明,在DMAP催化下,3a和5a可发生O-/N-酰基转移反应。     

胆酸甲酯羟基酰化反应活性研究

以甲基丙烯酰氯、甲基丙烯酸酐和甲基丙烯酸作酰化剂,研究了胆酸甲酯分子中羟基的反应活性.结果显示,与三种活性不同的酰化试剂作用时,胆酸甲酯分子甾体骨架上三个仲羟基的相对反应活性不同.     

(S)-4-羟基吡咯烷-2-酮的简便合成

(S)-3-羟基-γ-丁内酯开环制得手性3,4-二羟基丁酸甲酯(2);对2的伯羟基进行对甲苯磺酰化、仲羟基进行苄基保护得4-对甲苯磺酰氧基-3-苄氧基丁酸甲酯(5);5在氨甲醇作用下合环、脱苄基保护合成了(S)-4-羟基吡咯烷-2-酮,总收率26%,其结构经1HNMR和HR-MS确认,比旋光值与文献值相符。     

新型交联磺化聚醚偶酰酮的合成及其物理性能

以对氟苯甲醛为原料,依次经过安息香缩合、亲核取代和脱甲氧基化反应制得二酚类单体——4,4’-二[(4-羟基)苯氧基]-二苯偶酰(3);3与4,4’-联苯二酚和3,3’-二磺酸钠基-4,4’-二氟二苯甲酮进行亲核缩聚反应,合成了一系列链状磺化聚醚偶酰酮聚合物(6a～6d)并制得质子膜(F-6a～F-6d);以3,3’-二氨基联苯胺为交联剂,6a～6d经缩环反应合成了新型交联结构的磺化聚醚偶酰酮(8a～8d)并制得具有不同离子交换容量的质子膜(F-8a～F-8d),6a～6d与8a～8d的结构经1H NMR和IR表征。物理性能研究结果表明,F-8a～F-8d具有较高的热稳定性和质子传导率。     

8(或6)-氯-7-羟基-4-甲基香豆素及其衍生物的合成

以2(或4)-氯间苯二酚和乙酰乙酸乙酯为原料,通过Pechmann缩合反应,合成了新的8(或6)-氯-7-羟基-4-甲基香豆素(1a或1b); 1经硫酸二甲酯甲基化得2a或2b; 以四正丁基溴化铵作相转移催化剂,1经Williamson反应合成了6个新的氯代香豆素衍生物(3a～6a, 3b, 4b),产率66%～92%.1～6的结构经1H NMR, IR和GC-MS表征.     

含(1-芳乙酰胺基-2-叔胺基)乙烷结构的六氢-1H-1,4-二氮革类新化合物的合成(Ⅱ)

设计并合成了2-[1-(4-(N-苯基-N-丙酰基)氨基)哌啶基]甲基-六氢-1H-1,4-二氮 7.由3经还原、氯取代、胺取代、胺脱苄反应得到了7.7经单酰化反应得到了8.8经酰化反应后得到了11个带有(1-芳乙酰胺基-2-叔氨基)乙烷结构的六氢-1H-1,4-二氮类目标化合物(9a～9g,10a～10d).     

Thin-Layer Chromatography of Bile Alcohols,Bile Acids and Conjugated Bile Acids

Abstract

Thin-layer chromatography of bile alcohols, bile acids and bile acid conjugates has been reviewed. Particular emphasis has been placed on the separation of the glycine and taurine conjugated bile acids as a class and as individual compounds, and on the isolation of bile alcohols and C₂₇ bile acids diastereo-isomeric at C-25.     

胆汁酸衍生物三羰基铼核配合物的合成与表征

以胆酸、鹅去氧胆酸为起始原料, 经羧基的酯化、酯的胺解以及氨基的烷基化, 合成了一系列潜在的针对肝胆显像和肠显像的SPECT (Single photon emission computed tomography)分子探针前体. 该方法简便易行, 合成路线短, 产率高, 它们的结构已经过IR, 1H NMR, 13C NMR, HRMS和元素分析得到了证实. 这些结果为基于以胆汁酸为原料的放射性药物的研究奠定了基础.     

Characterization of bile acids and fatty acids from ox bile in oil paintings by gas chromatography-mass spectrometry

Characterization of ox bile, traditionally used in painting, is of interest in the fields of archaeometry and conservation and restoration of works of art. Bile acids, fatty acids (F), and cholesterol found in ox bile have been identified using a derivatization method that combines the formation of ethyl esters from the carboxylic groups and the trimethylsilyl ethers from hydroxyl groups. This method of analysis is consistent with these others proposed by the authors to analyze drying oils, proteins, and diterpenic resins usually used as binders and varnishes by the painters. Bile acids from binary samples such as animal glue/ox bile, casein/ox bile and Arabic gum/ox bile have been successfully analyzed using the proposed method. Finally, a method of analysis of mixtures of drying oil and ox bile has been also proposed attempting to quantitatively characterize samples in which ox bile was added to the drying oil for increasing the surfactant properties.     

The retention behaviour of conjugated bile acids in reversed phase high performance liquid chromatography.

The retention behaviour of conjugated bile acids has been studied in a reversed phase high performance liquid chromatographic (RP-HPLC) system by using the mixture of methanol and aqueous phosphate buffer as the mobile phase. The retentions of the conjugates in RP-HPLC have been found to be mainly controlled by the glycine and taurine groups. The selectivity between five different glycine and taurine conjugated bile acids is a constant in RP-HPLC. This selectivity has been used for peak identification in the practical separation of conjugated bile acids.     

Control of the enantioselectivity by keto bile acid derivatives in the epoxidation of alkenes with Oxone

The asymmetric epoxidation of unfunctionalized olefins has been achieved using 3-keto bile acids as optically active inducers and Oxone. Opposite enantioselectivities can be obtained depending on the specific substitution of the bile acids.     

Capillary gas chromatography/negative ion chemical ionization mass spectrometry for the quantification of bile acids including 1 beta-hydroxylated and unsaturated bile acids in serum and urine

12 bile acids, including 1 beta-hydroxylated and unsaturated bile acids, have been quantified by capillary gas chromatography/negative ion chemical ionization mass spectrometry, using the trimethylsilyl(TMS) ether derivatives of bile acid pentafluorobenzyl(PFB) esters. The analysis time is 12 min and the minimum measurable amount is 100 fg for each bile acid. Bile acids in 200 microL of serum and 50 microL of urine from healthy human adults were measured. These small sample sizes enhance the practicality of using this method as a screening test for bile acids in the serum and urine of human infants, where small sample size is a major problem.     

Probiotics—Interactions with Bile Acids and Impact on Cholesterol Metabolism

The use of probiotics, alone or in interaction with bile acids, is a modern strategy in the prevention and treatment of hypercholesterolemia. Numerous mechanisms for hypocholesterolemic effect of probiotics have been hypothesized, based mostly on in vitro evidence. Interaction with bile acids through reaction of deconjugation catalyzed by bile salt hydrolase enzymes (BSH) is considered as the main mechanism of cholesterol-lowering effects of probiotic bacteria, but it has been reported that microbial BSH activity could be potentially detrimental to the human host. There are several approaches for prevention of possible side effects associated with BSH activity, which at the same time increase the viability of probiotics in the intestines and also in food matrices. The aim of our study was to summarize present knowledge of probiotics??bile acids interactions, with special reference to cholesterol-lowering mechanisms of probiotics, and to report novel biotechnological approaches for increasing the pharmacological benefits of probiotics.     

Fluorescence high-performance liquid chromatographic determination of free and conjugated bile acids in serum and bile using 1-bromoacetylpyrene as a pre-labeling reagent

A fluorescence high-performance liquid chromatographic method is described for the determination of free and conjugated bile acids in serum and bile. Free and conjugated bile acids are extracted from serum or bile using a Sep-Pak C18 cartridge and then fractionated on a piperidinohydroxypropyl Sephadex LH-20 column. Free and glycine-conjugated bile acids are labeled with 1-bromoacetylpyrene in acetonitrile using dicyclohexyl-18-crown-6-ether as catalyst. Taurine-conjugated bile acids are hydrolyzed by cholylglycine hydrolase and then derivatized by the same reagent. Derivatized bile acids are separated stepwise on a reversed-phase column (Radial Pak A) using acetonitrile-methanol-water (A) (100 : 50 : 40) and (B) (100 : 50 : 20) as mobile phase. The eluate is monitored by a fluorophotometer at 370 nm (excitation) and 440 nm (emission). Linearities of fluorescence intensities (peak heights) with the amounts of free and conjugated bile acids were obtained between 50 pmol and 200 pmol for free bile acids and between 25 pmol and 100 pmol for glycine-conjugated bile acids, respectively. Recoveries from serum and bile samples are not less than 90%. This method is sensitive, reliable and useful for the simultaneous determination of free and conjugated bile acids in serum and bile.     

Improved method for the determination of the major neutral steroids and unconjugated bile acids in human faeces using capillary gas chromatography

An improved method has been developed for the determination of the major neutral steroids (cholesterol and 5 beta-cholestan-3 beta-ol) and unconjugated bile acids (deoxycholic acid and lithocholic acid) in human faeces, using capillary gas chromatography with flame ionization detection. The freeze-dried faecal sample was subjected to a two-stage Soxhlet extraction followed by an aqueous alkali-organic solvent partition step to separate neutral steroids from bile acids. The neutral steroids were analysed as their trimethylsilyl ether derivatives on an OV-1 capillary column. The bile acids were further purified on a Sep-Pak C18 cartridge and then fractionated on a Sep-Pak SIL cartridge. Unconjugated bile acids were analysed as their methyl ester-trimethylsilyl ether derivatives also on an OV-1 capillary column. Quantitation of neutral steroids and unconjugated bile acids was achieved by reference to appropriate internal standards, added to the faecal extract immediately after the Soxhlet extraction stage. The method is being used in a study of the effect of diet on the metabolic activity of human gut flora.     

胆酸盐参与的自组装及微纳米材料制备

胆酸盐类物质可看作是一类阴离子型甾族生物表面活性剂,鉴于其特殊的两亲性骨架结构、独特的物理化学性质及其良好的生物相容性和环境友好性,其在溶液中能够参与超分子自组装形成有序聚集结构,且可以作为模板在微纳材料制备领域有着重要应用。本文结合我们课题组的研究工作,综述了近期国内外相关研究,详细介绍了生物小分子氨基酸对胆酸盐聚集行为的影响、胆酸盐参与形成的超分子凝胶及胆酸盐参与构筑的微纳米材料制备等方面的研究进展,以期对胆酸盐参与的自组装及微纳米材料制备领域的研究有更全面更深入的了解,为后续的应用研究提供坚实的基础。