甾族化合物质谱数据库的建立及其应用

甾族化合物是一类广泛存在于动植物体内的天然有机化合物。许多甾族化合物都具有重要的生理作用。本文介绍的工作主要是在微机上建立了一个包含1700余张甾族化合物谱图的人机对活检索系统。其检索方式有单离子检索、分子式检索、分子量检索、基峰检索、谱图匹配检索。实验证明该系统对甾族化合物可提供良好的结构鉴定能力。     

D六元环甾族化合物(D-homo-steroids)

甾族化合物的五元 D 环,如式(Ⅰ)所示,变成六元D 环者,便称其为 D 环加碳甾族化合物,如式(Ⅱ)。在许多甾族化合物的侧链上,常常含有17-羟基20酮的构造(R=COCH_3,R_1=OH),具有这种构造以及其他类似结构的甾族物,遇碱或酸等试剂,往往会发生分子内的重排,其结果使 D 环扩大而成六元 D 环;最近发现了某些 D 环加碳甾族物具有特殊的生理作用,     

甾族化合物A环上的异构现象及NMR谱

在几个甾体生物碱中发现甾族化合物A环上存在有构象异构现象;应用NMR技术对该现象作了深入研究,还测定了互变异构体的活化自由能。这一现象的发现为甾族化合物的构象研究增添了新的内容。     

氚核磁共振波谱在氚标记甾族化合物制备中的应用

本文介绍了十一种氚化甾族化合物的氚核磁共振谱。我们依照英国放化中心和英国萨里大学报道数据,(甾体骨架上的CH及CH_2各位置的谱线归属,应用了定位标记化合物作为对照)归属了其氚在化合物中标记的位置,根据其积分曲线定出了各位氚的相对百分含量。同时图谱中又提供了立体构型的信息,为氚化甾族化合物制备过程中,催化剂的选择,实验条件的控制及反应机理等研究提供了理论依据。     

通光藤中一个新C21甾族化合物的化学结构测定

从通光藤中分离到一个新的C₂₁甾族化合物(晶A),通过物理和化学方法确定了它的结构.该甾族化合物的结构特点为B,C环系顺式镶合,缩酮的两个氧环与C,D环共同组成了一个牢固的笼式结构,这是天然化合物中比较少见的一种结构.晶A命名为通光素,其化学名称为5α,17α-孕甾-3β,8α,11α,12β,14β-五醇-20-酮-8,11-缩酮.     

甾族化合物命名方法底介绍

甾族化合物Steroid底系統研究是在廿世紀才開始的,它的歷史雖然很短,可是進步却很快。为着便於學習和研究,我們需要較為有系統而合理的名稱。在英文中甾族化合物通用的名稱是沒有系統的:有的是從其來源命名,如cholic acid,ergosterol等是;有的是按其特殊生理作用來     

甾族化合物差向异构体的~(13)C光谱分析

七十年代对於甾族化合物的CNMR谱研究主要采用质子噪音去偶、偏共振去偶、相关化合物比较,辅以同位素标记、镧系化学位移试剂和弛豫时间等技术。质子噪音去偶~(13)C谱具有谱线简单和灵敏度高等特点,但失去了偶合信息。偏共振去偶谱保留了偶合信息,得到的J~r值虽较真正的~1J_(CH)值要小,一般说来能较有效地区分碳原子类型,但对甾族化合物因偶合的多重谱线彼此重叠,降低了用偏共振谱指配的有效性。目前,对於复杂化合物的~(13)C谱     

天然有机物合成的艺术性

我国化学会创建的前夕(1933),正是胆酸及胆甾醇正确结构式建立的年代(1932)。从那时起,不断地发现许多极为重要的生理活性物质,它们都是甾族化合物。试想激素、维生素、毒素、生物碱以及重要的药物,其中包括避孕药片,哪一样没有包含一个甾族的基本碳架环戊烯稠菲呢?它在有机化学中的普遍性,如     

Shapiro 1,2-酮基移位反应的研究

本文利用Shapiro反应的1,2-酮基移位反应, 经过五步使甾族化合物的6α-羟基移位到7α-羟基. 总产率是13 ％.     

构象最小改变原理

一、前言 Barton在1950年研究甾族化合物等具有刚性构象的稠环化合物时,注意到在椅型构象的环己烷环系上,处于α-键向位的羟基和卤原子等比较活泼,容易发生消除反应等,根据当时     

Total steroid profiling with capillary GC. Details on sample preparation

The accuracy and reproducibility of steroid and steroid conjugate determinations using capillary GC are evaluated. It is possible to analyze many unconjugated steroids, steroid sulfates, and some steroid glucuronides simultaneously, simply by using group fractionation based on successive hydrolysis and solvent extraction steps. However, a reliable determination of corticosteroid glucuronides can only be obtained after previous isolation of the glucuronides as a group, with ion exchange chromatography. In complex chromatograms, the combined use of nitrogen specific detection and flame ionization detection facilitates peak identification.     

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.     

Stable isotope labeling – Liquid chromatography/mass spectrometry for quantitative analysis of androgenic and progestagenic steroids

Steroid hormones play important roles in mammal at very low concentrations and are associated with numerous endocrinology and oncology diseases. Therefore, quantitative analysis of steroid hormones can provide crucial information for uncovering underlying mechanisms of steroid hormones related diseases. In the current study, we developed a sensitive method for the detection of steroid hormones (progesterone, dehydroepiandrosterone, testosterone, pregnenolone, 17-hydroxyprogesterone, androstenedione and 17α-hydroxypregnenolone) in body fluids by stable isotope labeling coupled with liquid chromatography-electrospray ionization-tandem mass spectrometry (LC-ESI-MS/MS) analysis. In this respect, a pair of isotopes labeling reagents, Girard reagent P (GP) and d₅-Girard reagent P (d₅-GP), were synthesized and utilized to label steroid hormones in follicular fluid samples and steroid hormone standards, respectively. The heavy labeled standards were used as internal standards for quantification to minimize quantitation deviation in MS analysis due to the matrix and ion suppression effects. The ionization efficiencies of steroid hormones were greatly improved by 4–504 folds through the introduction of a permanent charged moiety of quaternary ammonium from GP. Using the developed method, we successfully quantified steroid hormones in human follicular fluid. We found that the contents of testosterone and androstenedione exhibited significant increase while the content of pregnenolone had significant decrease in follicular fluid of polycystic ovarian syndrome (PCOS) patients compared with healthy controls, indicating that these steroid hormones with significant change may contribute to the pathogenesis of PCOS. Taken together, the developed stable isotope labeling coupled LC-ESI-MS/MS analysis demonstrated to be a promising method for the sensitive and accurate determination of steroid hormones, which may facilitate the in-depth investigation of steroid hormones related diseases.     

Study of urinary steroid hormone disorders: difference between hepatocellular carcinoma in early stage and cirrhosis

Hepatocellular carcinoma (HCC) is the fifth most common cancer in the world. Discovery of novel biomarkers for early HCC from other liver diseases such as cirrhosis is of great clinical benefit. In this study, a novel steroid hormone metabolomic method based on liquid chromatography–mass spectrometry combined with logistic regression analysis was applied to study the steroid hormone disorders and to screen potential urinary steroid hormone biomarkers of early HCC. Thirty-six urinary steroid hormones were detected and quantified in healthy controls, cirrhotic patients, and early HCC patients. Heat map analysis and multivariate statistical analysis suggested severe disorders of steroid hormone network and holistically decreased urinary steroid hormone pattern in cirrhotic and early HCC patients. Logistic regression analysis reveals that a panel of two urinary steroid hormones (epitestosterone and allotetrahydrocortisol) displayed excellent diagnostic capability for distinguishing early HCC from cirrhosis with area under the curve (AUC)?=?0.938 of receiver operating characteristic (ROC) analysis. These results help to overcome the disadvantage of lower sensitivity and specificity of alpha-fetoprotein for distinguishing early HCC from cirrhosis. Our work shows that steroid hormone metabolomics is a promising biomarker tool for biomarker study of early HCC.

A new flexible synthesis of (D-homo) steroids

A short, flexible and efficient procedure has been developed for the synthesis of C17 substituted steroid skeletons and D-homo steroid skeletons using a ZnBr₂ catalysed coupling of a silyl enol ether containing ring D precursor with a Torgov type reagent, followed by acid catalysed cyclisation of the adducts to (D-homo) steroid skeletons.     

Novel analytical methods for the determination of steroid hormones in edible matrices

This paper reviews recently published multi-residue chromatographic methods for the determination of steroid hormones in edible matrices. After a brief introduction on steroid hormones and their use in animal fattening, the most relevant EU legislation regarding the residue control of these substances is presented. An overview of multi-residue analytical methods, covering sample extraction and purification as well as chromatographic separation and different detection methods, being in use for the determination of steroid hormones (estrogens, gestagens and androgens), is provided to illustrate common trends and method variability. Emphasis was laid on edible matrices and more specifically on meat, liver, kidney, fat and milk. Additionally, the possibilities of novel analytical approaches are discussed. The review also covers specific attention on the determination of natural steroids. Finally, the analytical possibilities for phytosterols, naturally occurring steroid analogues of vegetable origin and a specific group of steroid hormones with a hemi-endogenous status are highlighted.     

3Alpha,7alpha,12alpha-triacetoxy-5beta-cholanic acid, a steroid from the Formosan soft coral Alcyonium sp. (Alcyoniidae)

Chemical investigation of the organic extract of a soft coral belonging to the genus Alcyonium furnished a steroid, 3alpha,7alpha,12alpha-triacetoxy-5beta-cholanic acid (1). The structure of steroid 1 was assigned on the basis of spectroscopic evidence, particularly in 1D and 2D NMR experiments. The configuration of steroid 1 was further supported by molecular mechanics calculations.     

Rapid and sensitive analysis of phthalate metabolites, bisphenol A, and endogenous steroid hormones in human urine by mixed-mode solid-phase extraction, dansylation, and ultra-performance liquid chromatography coupled with triple quadrupole mass spectrometry

Steroid hormone levels in human urine are convenient and sensitive indicators for the impact of phthalates and/or bisphenol A (BPA) exposure on the human steroid hormone endocrine system. In this study, a rapid and sensitive method for determination of 14 phthalate metabolites, BPA, and ten endogenous steroid hormones in urine was developed and validated on the basis of ultra-performance liquid chromatography coupled with electrospray ionization triple quadrupole mass spectrometry. The optimized mixed-mode solid phase-extraction separated the weakly acidic or neutral BPA and steroid hormones from acidic phthalate metabolites in urine: the former were determined in positive ion mode with a methanol/water mobile phase containing 10 mM ammonium formate; the latter were determined in negative ion mode with a acetonitrile/water mobile phase containing 0.1 % acetic acid, which significantly alleviated matrix effects for the analysis of BPA and steroid hormones. Dansylation of estrogens and BPA realized simultaneous and sensitive analysis of the endogenous steroid hormones and BPA in a single chromatographic run. The limits of detection were less than 0.84 ng/mL for phthalate metabolites and less than 0.22 ng/mL for endogenous steroid hormones and BPA. This proposed method had satisfactory precision and accuracy, and was successfully applied to the analyses of human urine samples. This method could be valuable when investigating the associations among endocrine-disrupting chemicals, endogenous steroid hormones, and relevant adverse outcomes in epidemiological studies.

Urinary steroid analysis of women with effluvium

Summary Urinary steroid metabolites were measured by capillary gas chromatography in 25 women (aged 33.3±12.0 years) with effluvium and 16 control healthy laboratory workers women (aged 34.6±8.4 years). There was significant elevation in the level of a number of steroids and steroid metabolites. The elevation of most steroid metabolites refers to the increased steroid secretion of the adrenal and the high cortisol metabolites levels may be do to stress in some of the patients with effluvium. Presented at: Balaton Symposium on High-Performance Separation Methods, Siófok, Hungary, September 3–5, 1997     

Preparation of an analogue of orbicuside A,an unusual cardiac glycoside

A steroid containing a multi-linked glycoside, analogous to the bufadienolide orbicuside A, has been prepared. The key steps were (i) the preparation of a 2α-allyloxycarbonyloxy-3β-hydroxy steroid, (ii) a Ferrier reaction between the steroid and a rhamnal derivative, (iii) removal of protecting group and oxidation of the 2-hydroxy group, (iv) dihydroxylation of the pseudoglycal from the sterically more hindered side and finally (v) ring closure by acetal formation under acidic conditions.