Three New Polyoxygenated Steroids from Two Species of the South China Sea Gorgonian Muricella flexuosa and Menella verrucosa Brundin

Three new polyoxygenated steroids, muricesteroid ( 1 ), and menellsteroids A ( 2 ) and B ( 3 ), were isolated from two species of the South China Sea gorgonian Muricella flexuosa and Menella verrucosa Brundin , respectively. The structures of these new compounds were elucidated on the basis of extensive spectroscopic analysis, chemical methods and comparison with known related compounds.     

Stemmosides C and D, two novel unusual pregnane glycosides from Solenostemma argel: structural elucidation and configurational study by a combined NMR-quantum mechanical strategy

Stemmosides C and D, two novel pregnane glycosides characterized by an unusual C-17 side chain were isolated from the pericarps of Solenostemma argel. In addition, stemmoside D displays an uncommon 14β proton configuration, apparently being the first pregnane isolated from plants known to have a 15 keto, cis CD ring junction. Their structures have been established by ESIMS and NMR experiments. The relative configuration of the molecules was determined using a strategy based on the simulation of ¹H, ¹³C, and J coupling NMR parameters. DFT calculations of ¹H and ¹³C chemical shifts, and of the ¹H homonuclear spin–spin coupling constants were performed with the mPW1PW91 functional using the 6-31G(d,p) basis set on the fully optimized geometries of all the possible stereoisomers.     

Photochemistry of some steroidal bicyclo[3.1.0]hexenones

The photochemistry of five 11-hydroxy-1,5-cyclopregn-3-en-2-ones (‘lumi’ products from the corresponding pregna-1,4-dien-3-ones) has been investigated. In all cases the photoproducts were 1,11-oxy derivatives, resulting from intramolecular attack of the hydroxyl group to the incipient positive charge at C-1. When a fluorine atom was present at C-6, HF elimination took place concurrently with the nucleophilic addition and led to linearly conjugated dienones, rather than the enones obtained in the other cases. Quantum yields were in the range 0.06-0.2, the lower values applying when a fluorine atom was present in position 6 (not in position 9). The results add new evidence on the role of zwitterionic intermediates in the photochemistry of cross-conjugated dienones and the corresponding lumi photoproducts.     

一种利用质谱信息进行结构特征鉴定的模式识别方法

本文提出了分段式离子系列谱编码方法,实验证明具有很好的结构表征能力。本程序主要是以模式识别技术为基础,实现了对未知物谱图的KNN分类,进而得到未知物的主要结构特征。这个程序应用于有机化合物的分类,取得了满意的结果。     

π‐Facial Selectivity in the Formation of Tricarbonylchromium(0) Complexes of Estra‐1, 3, 5(10), 6‐tetraenes

The preparation of two η⁶‐estra‐1, 3, 5(10), 6‐tetraene tricarbonylchromium complexes 4 and 6 are described. In both cases only one stereoisomer can be isolated, in contrast to other estrane‐tricarbonylchromium complexes, where complexations are non‐stereoselective. X‐ray crystal structural analysis of 4 discloses that only the more sterically hindered β‐facial isomer is formed. It is assumed that the 6, 7‐olefinic moiety exerts a directive influence on the complexation.     

Synthesis of Novel <Emphasis Type="Italic">D</Emphasis>-<Emphasis Type="Italic">Seco</Emphasis>-Pregnenes

Summary. A new synthetic route was developed for the preparation of trans-3-hydroxy-16,17-seco-pregna-5,17(20)-dien-16-al, using Grob fragmentation as the key step. This seco-steroid contains a formyl group and an unsaturated side-chain in a sterically favourable position, and is therefore a promising starting material for the synthesis of novel condensed steroid heterocycles.Received March 22, 2003; accepted April 22, 2003 Published online September 25, 2003     

Structural determinants of steroids for cytochrome P450 3A4-mediated metabolism

Cytochrome P450 3A4 (CYP3A4), a major member of cytochrome P450 isoenzymes, metabolizes the majority of steroids in 6β-position. For the purpose of determining requisite structural features of a series of structurally related steroids for CYP3A4-mediated metabolism, three-dimensional pharmacophore modeling as well as electrotopological state map were conducted for 15 steroids. Though prior studies speculated that the chemical reactivity of the allylic 6β-position might have a greater influence on CYP3A4 selective 6-hydroxylation than steric constraints in the enzyme, our results reveal that for CYP3A4 steroidal substrates, it is not the chemical reactivity of atoms at 6β-site, but the pharmacophoric features, i.e. the two hydrophobic rings together with two H-bond donors, that act as the key factors responsible for determining the CYP3A4 selective 6-hydroxylation of steroids.     

Fast screening of anabolic steroids and other banned doping substances in human urine by gas chromatography/tandem mass spectrometry

A fast and sensitive method for the comprehensive screening of anabolic agents and other banned doping substances using gas chromatography/tandem mass spectrometry (GC/MS/MS) with an external ionization ion trap mass spectrometer is presented. The method takes advantage of the resolving power of MS/MS to eliminate background interferences, thus speeding up the chromatographic analysis. For each compound, different fragmentation reactions were studied and their collision energies optimized to obtain the best sensitivity in terms of their signal-to-noise ratio (S/N). A dramatic reduction in overall analysis time was achieved compared with other common approaches. More than 50 substances could finally be monitored in less than 7.4 min with detection limits (S/N >3) lower than 0.5 ng ml(-1) for most of the compounds with special sensitivity requirements according to the International Olympic Committee (IOC). A validation procedure for qualitative analysis was performed. The selectivity of the method showed that no interfering peaks were observed at the retention time of the analytes. Good intermediate precision, below 25% for most of the compounds, and robustness were observed. The optimized method was successfully applied to analyse more than 100 real human urine samples with optimum sensitivity and specificity rates.     

Normal-phase high-performance liquid chromatographic separations using ethoxynonafluorobutane as hexane alternative. II. Liquid chromatography-atmospheric pressure chemical ionization-mass spectrometry applications with methanol gradients

We have reported recently that high-speed normal-phase (NP) HPLC separations of a broad range of organic compounds can be performed on cyano columns using gradients of methanol in hexane-like solvent-ethoxynonafluorobutane (ENFB), available commercially. In this communication, we demonstrate that atmospheric pressure chemical ionization (APCI) in combination with mass spectrometry (MS) can be effectively used for detection in such separations. The efficiency of APCI under conditions studied has also been compared to the efficiency of traditional electrospray ionization (ESI) in combination with MS for reversed-phase (RP) HPLC of the same compounds. The compounds included in this study were steroids, benzodiazepines, and other central nervous system-active substances, nonsteroidal anti-inflammatory drugs, tricyclic antidepressants, and beta-adrenergic blocking agents. Non-polar compounds were found to respond stronger when APCI-MS technique was used, whereas APCI and ESI ionization efficiencies were comparable when polar substances were studied. The combination of normal-phase HPLC separation conditions with mass spectral detection may expand the range of LC-MS applications traditionally associated with reversed-phase HPLC and ESI-MS detection.     

Role of the solvent in thin-layer chromatography of steroids on alumina

The effects of different binary solvents on the retention behaviour of some steroids in thin-layer chromatography on alumina were studied. The slope of the linear relationship between the retention constant of the steroid and the logarithm of the volume fraction fo the polar component in the binary solvent mixture depends predominantly on the diluent. Linear relationships between the axis intercepts and slopes of particular steroids exists for all chromatographic systems examined. The slope of this relationships is a function of the retention constant of the steroid hydroxyl group.