dc.description.abstract
The abuse of performing enhancing drugs has been an issue since the invention of competitive sports. With the advent of modern biochemistry the potential performance gain was ever increased, for example by stimulants, anabolic agents and growth hormones.[1,2]
On the World Anti-Doping Agency (WADA) prohibited substance class list also agents with anti-oestrogenic activity (e.g. SERM) are considered performance-enhancing. The reason for this lies in the masking or mitigating of negative side-effects attributed to the use of anabolic androgenic steroids (AAS) in their training regimen.[1,3,4]
As the identification of doping agents is vital to prove this kind of substance abuse for professional athletes, metabolic studies are required to determine which metabolites are most prominent and preferably detectable over long periods of time. Metabolites are often oxidised, reduced, hydrolysed, and hydrated (phase I metabolism) or glucuronidated and sulphated compounds (phase II metabolism), transforming the doping agent into a less toxic, often less active and more hydrophilic form.[5–7]
In this work, we present the synthesis of a complex tamoxifen metabolite through palladium catalyzed alpha-arylation followed by phenyl grignard addition and subsequent stereoselective dehydration to construct the tetrasubstituted olefin in 6 steps. Furthermore, studies of several glucuronidation methods, such as Schmidt glycosylation and Yu glycosylation, towards the synthesis of different steroidal glucuronides, were conducted.
Literature:
[1] W. Schänzer, M. Thevis, Med. Klin. 2007, 102, 631–646. [2] A. J. Schneider, T. Friedmann, in Adv. Genet., Academic Press, 2006, pp. 1–9. [3] M. C. Farrar, T. F. Jacobs, in StatPearls, StatPearls Publishing, Treasure Island (FL), 2024. [4] B. Claude, P. Morin, S. Bayoudh, J. de Ceaurriz, J. Chromatogr. A 2008, 1196–1197, 81–88. [5] C. Gómez, O. J. Pozo, R. Diaz, J. V. Sancho, E. Vilaroca, J. P. Salvador, M. P. Marco, F. Hernandez, J. Segura, R. Ventura, J. Chromatogr. A 2011, 1218, 4727–4737. [6] T. Kuuranne, Handb. Exp. Pharmacol. 2010, 65–75. [7] G. G. G. A. P. SKETT, Introduction to Drug Metabolism, Springer, 2013.
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