Synthese von 20ßOH-NorMD, ein mit dem Harn ausgeschiedener Langzeitmetabolit von Metandienone

Abweichender Titel nach Übersetzung der Verfasserin/des VerfassersThe goal of this thesis was a good-yielding chemical synthesis of a metandienone metabolite which is of interest in doping analysis. Compound 20ßOH-NorMD (IUPAC: 17ß-hydroxymethyl-17--methyl-18-norandrosta-1,4,13-triene-3-one) has been identified as a long-term urinary metabolite which can be detected and attributed to metandienone up to almost 3 weeks after exposure. The chemical synthesis of another isomer: 20-OH-NorMD has been described before by Parr et al.; Zöllner et al. reported a chemoenzymatic way to 20ßOH-NorMD but no chemical synthesis was yet published.4

Recent advances in the dearomative functionalisation of heteroarenes

Dearomatisation reactions of (hetero)arenes have been widely employed as efficient methods to obtain highly substituted saturated cyclic compounds for over a century. In recent years, research in this area has shifted towards effecting additional C–C bond formation during the overall dearomative process. Moving away from classical hydrogenation-based strategies a wide range of reagents were found to be capable of initiating dearomatisation through nucleophilic addition (typically a reduction) or photochemically induced radical addition. The dearomatisation process gives rise to reactive intermediates which can be intercepted in an intra- or intermolecular fashion to deliver products with significantly increased molecular complexity when compared to simple dearomatisation. In this Perspective recent examples and strategies for the dearomative functionalisation of heteroaromatic systems will be discussed

Total synthesis of [13C2]-labelled phytosiderophores of the mugineic and avenic acid families

We herein report the synthesis of 13C2-labelled natural products from the mugineic acid and avenic acid family. These phytosiderophores (“plant iron carriers”) are built up from non-proteinogenic amino acids and play a key role in micronutrient uptake in gramineous plants. In this work two central building blocks are prepared from labelled starting materials (13C2-bromoacetic acid, 13C2-glycine) and further employed in our recently reported divergent, branched synthetic strategy delivering eight isotopically labelled phytosiderophores. The required labelled building blocks (13C2-L-allylglycine and a related hydroxylated derivative), were prepared via enantioselective phase-transfer catalysis and enantio- and diastereoselective aldol condensation with a chiral auxiliary respectively, both potentially valuable themselves for other synthetic routes towards labelled (natural) products

Development and validation of a simple online-SPE method coupled to high-resolution mass spectrometry for the analysis of stanozolol-N-glucuronides in urine samples

Stanozolol is still the most commonly used illicit anabolic‐androgenic steroid (AAS) in professional sports. Therefore, accurate and fast analysis and long detection windows are of great interest in the field of antidoping analysis. In this work, a very simple, fast, and highly sensitive online solid‐phase extraction method coupled with liquid chromatography–high‐resolution tandem mass spectrometry (HPLC‐HRMSMS) for the analysis of stanozolol‐N‐glucuronides was developed. This fully validated procedure is characterized by only a few manual steps (dilution and addition of internal standard) in the sample preparation. A limit of identification (LOI) of 75 pg/mL, high accuracy (87.1%–102.1%), precision (3.1%–7.8%), and sensitivity was achieved. Furthermore, good linearity (> 0.99) and robustness, as well as no carry‐over effects, could be observed. In addition to excellent confirmation analysis performance, this method shows sufficient potential for the identification and characterization of unknown metabolites. Using this method, it was possible to unambiguously confirm the presence of 1′N‐ and 2′N‐stanozolol‐glucuronide in human urine for the first time due to the access to reference material

Development and validation of a simple online‐SPE method coupled to high‐resolution mass spectrometry for the analysis of stanozolol‐N‐glucuronides in urine samples

Stanozolol is still the most commonly used illicit anabolic‐androgenic steroid (AAS) in professional sports. Therefore, accurate and fast analysis and long detection windows are of great interest in the field of antidoping analysis. In this work, a very simple, fast, and highly sensitive online solid‐phase extraction method coupled with liquid chromatography–high‐resolution tandem mass spectrometry (HPLC‐HRMSMS) for the analysis of stanozolol‐N‐glucuronides was developed. This fully validated procedure is characterized by only a few manual steps (dilution and addition of internal standard) in the sample preparation. A limit of identification (LOI) of 75 pg/mL, high accuracy (87.1%–102.1%), precision (3.1%–7.8%), and sensitivity was achieved. Furthermore, good linearity (> 0.99) and robustness, as well as no carry‐over effects, could be observed. In addition to excellent confirmation analysis performance, this method shows sufficient potential for the identification and characterization of unknown metabolites. Using this method, it was possible to unambiguously confirm the presence of 1′N‐ and 2′N‐stanozolol‐glucuronide in human urine for the first time due to the access to reference material

Phytosiderophore pathway response in barley exposed to iron, zinc or copper starvation

Efficient micronutrient acquisition is a critical factor in selecting micronutrient dense crops for human consumption. Enhanced exudation and re-uptake of metal chelators, so-called phytosiderophores, by roots of graminaceous plants has been implicated in efficient micronutrient acquisition. We compared PS biosynthesis and exudation as a response mechanism to either Fe, Zn or Cu starvation. Two barley (Hordeum vulgare L.) lines with contrasting micronutrient grain yields were grown hydroponically and PS exudation (LC-MS) and root gene expression (RNAseq) were determined after either Fe, Zn, or Cu starvation. The response strength of the PS pathway was micronutrient dependent and decreased in the order Fe &gt; Zn &gt; Cu deficiency. We observed a stronger expression of PS pathway genes and greater PS exudation in the barley line with large micronutrient grain yield suggesting that a highly expressed PS pathway might be an important trait involved in high micronutrient accumulation. In addition to several metal specific transporters, we also found that the expression of IRO2 and bHLH156 transcription factors was not only induced under Fe but also under Zn and Cu deficiency. Our study delivers important insights into the role of the PS pathway in the acquisition of different micronutrients.</p