1156-92-9Relevant articles and documents
Steroidal isomers with uniform mass spectra of their per-TMS derivatives: Synthesis of 17-hydroxyandrostan-3-ones, androst-1-, and -4-ene-3,17-diols
Parr, Maria K.,Zapp, Josef,Becker, Michael,Opfermann, Georg,Bartz, Ulrike,Schaenzer, Wilhelm
, p. 545 - 551 (2007)
In human sports doping control analysis most of the steroids are analyzed after enzymatic hydrolysis of the glucuronides as per-trimethylsilyl (TMS) derivatives applying gas chromatography-mass spectrometry (GC-MS). According to the recommendations of the World Anti-Doping Agency the identification of analytes should be based on retention time and on mass spectrometric characterization. This study shows that the bis-TMS derivatives of 16 specific C19 steroids, namely the stereoisomers of 5ξ-androst-1-ene-3ξ,17ξ-diol (8 isomers), androst-4-ene-3ξ,17ξ-diol (4 isomers), and 17ξ-hydroxy-5ξ-androstan-3-one (4 isomers), reveal very similar mass spectra. As a rule, when taking the retention times, which are provided as Kovac indices for all these isomers, into account, a restriction to two or three possible isomers is possible. Reliable identification should additionally include a comparison of the retention times of the analytes with the reference compounds measured concomitantly. In some cases standard addition may be appropriate. Due to the limited availability, the above mentioned isomers were synthesized by reduction of the corresponding α,β-unsaturated oxo steroids either with K-Selectride or by catalytic hydrogenation (Pd/C as catalyst). The products of the reactions were identified by means of nuclear magnetic resonance (NMR) characterization and by further reduction to the corresponding 5ξ-androstane-3ξ,17ξ-diols and GC-MS comparison with commercially available reference standards.
Concerning the pathway from 19-oxoandrost-4-ene-3,17-dione
Caspi, Eliahu,Njar, Vincent C. O.
, p. 347 - 362 (1987)
The conversion of a molecule of 19-oxoandrost-4-ene-3,17-dione to estrone by human placental aromatase requires a molecule of oxygen and NADPH.An atom of this molecule of oxygen is incorporated into the extruded formic acid derived from C-19 af .It was proposed that the O2 is utilized for the enzymatic 2β-hydroxylation of and the released intermediate 2β-hydroxy-19-oxoandrost-4-ene-3,17-dione aromatizes nonenzymatically.Should be an obligatory intermediate of estrogen biosynthesis, then all the oxygen of its 2β-hydroxyl must be incorporated into the extruded formic acid.We have previously synthesized 18O;19-3H> and proved that none of its 2β-18O was incorporated in the formic acid extruded in the aromatization.On this basis we concluded that can not be an obligatory precursor of estrogen biosynthesis.The trapping of radioactive androst-4-ene-2β,3β,17β,19-tetrol in a reductively terminated incubation of a mixture of radioactive androst-4-ene-3,17-dione and with crude placental aromatase was interpreted as evidence in support of the intermediacy of .We confirmed that the terol can indeed be trapped in the reductively terminated incubations.However, considering that the crude placental enzyme preparation very likely contains numerous activated oxygen species capable of a variety of oxidation reactions, most of which may not be related to estrogen elaboration, and in view of our results qoted above, the origin and the eventual biosynthetic role of the parent compound of the tetrol remains to be determined.
Concerning the addition of chlorazide and bromazide to 3-keto-delta-4-steroids
Drefahl,Ponsold,Eichhorn
, p. 1633 - 1642 (1968)
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The Reduction of Steroid 2α-Fluoro 4-En-3-ones
Goeendos, Gyoergy,McGirr, Larry G.,Jablonski, Chester R.,Snedden, Walter,Orr, James C.
, p. 3057 - 3059 (1988)
Reduction of testosterone with potassium tri-(R,S)-sec-butylborohydride gives predominantly the allylic 3β-alcohol, while 2α-fluorotestosterone is converted solely to 2α-fluoro-4-androstene-3α,17β-diol, and 2α-fluoro-4-androstene-3,17-dione to 2α-fluoro-3α-hydroxy-4-androsten-17-one.Reduction of testosterone with (R,R)- or (S,S)-Rh-DIOP and dihydrosilanes give predominantly allylic alcohols, while with the same catalysts and monohydrosilanes no allylic alcohols are found, the 4-double bond being instead reduced.The chirality of the DIOP reagents contributes only to a minor extent to stereoselectivity of 3-ketone reduction.
Boosting the Catalytic Performance of Metal–Organic Frameworks for Steroid Transformations by Confinement within a Mesoporous Scaffold
Cirujano, Francisco G.,Luz, Ignacio,Soukri, Mustapha,Van Goethem, Cedric,Vankelecom, Ivo F. J.,Lail, Marty,De Vos, Dirk E.
, p. 13302 - 13306 (2017)
Solid-state crystallization achieves selective confinement of metal–organic framework (MOF) nanocrystals within mesoporous materials, thereby rendering active sites more accessible compared to the bulk-MOF and enhancing the chemical and mechanical stability of MOF nanocrystals. (Zr)UiO-66(NH2)/SiO2 hybrid materials were tested as efficient and reusable heterogeneous catalysts for the synthesis of steroid derivatives, outperforming the bulk (Zr)UiO-66(NH2) MOF. A clear correlation between the catalytic activity of the dispersed Zr sites present in the confined MOF, and the loading of the mesoporous SiO2, is demonstrated for steroid transformations.
Synthesis of steroid bisglucuronide and sulfate glucuronide reference materials: Unearthing neglected treasures of steroid metabolism
Pranata, Andy,Fitzgerald, Christopher C.,Khymenets, Olha,Westley, Erin,Anderson, Natasha J.,Ma, Paul,Pozo, Oscar J.,McLeod, Malcolm D.
supporting information, p. 25 - 40 (2019/01/04)
Doubly or bisconjugated steroid metabolites have long been known as minor components of the steroid profile that have traditionally been studied by laborious and indirect fractionation, hydrolysis and gas chromatography-mass spectrometry (GC–MS) analysis. Recently, the synthesis and characterisation of steroid bis(sulfate) (aka disulfate or bis-sulfate) reference materials enabled the liquid chromatography-tandem mass spectrometry (LC–MS/MS) study of this metabolite class and the development of a constant ion loss (CIL) scan method for the direct and untargeted detection of steroid bis(sulfate) metabolites. Methods for the direct LC–MS/MS detection of other bisconjugated steroids, such as steroid bisglucuronide and mixed steroid sulfate glucuronide metabolites, have great potential to reveal a more complete picture of the steroid profile. However, access to steroid bisglucuronide or sulfate glucuronide reference materials necessary for LC–MS/MS method development, metabolite identification or quantification is severely limited. In this work, ten steroid bisglucuronide and ten steroid sulfate glucuronide reference materials were synthesised through an ordered combination of chemical sulfation and/or enzymatic glucuronylation reactions. All compounds were purified and characterised using NMR and MS methods. Chemistry for the preparation of stable isotope labelled steroid {13C6}-glucuronide internal standards has also been developed and applied to the preparation of two selectively mono-labelled steroid bisglucuronide reference materials used to characterise more completely MS fragmentation pathways. The electrospray ionisation and fragmentation of the bisconjugated steroid reference materials has been studied. Preliminary targeted ultra-high-performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) analysis of the reference materials prepared revealed the presence of three steroid sulfate glucuronides as endogenous human urinary metabolites.
