2136-36-9Relevant academic research and scientific papers
Predictable Selectivity in Remote C?H Oxidation of Steroids: Analysis of Substrate Binding Mode
Olivo, Giorgio,Capocasa, Giorgio,Ticconi, Barbara,Lanzalunga, Osvaldo,Di Stefano, Stefano,Costas, Miquel
, p. 12703 - 12708 (2020)
Predictability is a key requirement to encompass late-stage C?H functionalization in synthetic routes. However, prediction (and control) of reaction selectivity is usually challenging, especially for complex substrate structures and elusive transformations such as remote C(sp3)?H oxidation, as it requires distinguishing a specific C?H bond from many others with similar reactivity. Developed here is a strategy for predictable, remote C?H oxidation that entails substrate binding to a supramolecular Mn or Fe catalyst followed by elucidation of the conformation of the host-guest adduct by NMR analysis. These analyses indicate which remote C?H bonds are suitably oriented for the oxidation before carrying out the reaction, enabling prediction of site selectivity. This strategy was applied to late-stage C(sp3)?H oxidation of amino-steroids at C15 (or C16) positions, with a selectivity tunable by modification of catalyst chirality and metal.
Novel steroid inhibitors of glucose 6-phosphate dehydrogenase
Hamilton, Niall M.,Dawson, Martin,Fairweather, Emma E.,Hamilton, Nicola S.,Hitchin, James R.,James, Dominic I.,Jones, Stuart D.,Jordan, Allan M.,Lyons, Amanda J.,Small, Helen F.,Thomson, Graeme J.,Waddell, Ian D.,Ogilvie, Donald J.
, p. 4431 - 4445 (2012/09/11)
Novel derivatives of the steroid DHEA 1, a known uncompetitive inhibitor of G6PD, were designed, synthesized, and tested for their ability to inhibit this dehydrogenase enzyme. Several compounds with approximately 10-fold improved potency in an enzyme assay were identified, and this improved activity translated to efficacy in a cellular assay. The SAR for steroid inhibition of G6PD has been substantially developed; the 3β-alcohol can be replaced with 3β-H-bond donors such as sulfamide, sulfonamide, urea, and carbamate. Improved potency was achieved by replacing the androstane nucleus with a pregnane nucleus, provided a ketone at C-20 is present. For pregnan-20-ones incorporation of a 21-hydroxyl group is often beneficial. The novel compounds generally have good physicochemical properties and satisfactory in vitro DMPK parameters. These derivatives may be useful for examining the role of G6PD inhibition in cells and will assist the future design of more potent steroid inhibitors with potential therapeutic utility.
A novel scalable and stereospecific synthesis of 3α- and 3β-amino-5α-androstan-17-ones and 3α- and 3β-amino- 5α-pregnan-20-ones
Hitchin, James R.,Hamilton, Niall M.,Jordan, Allan M.,Lyons, Amanda J.,Ogilvie, Donald J.
, p. 2868 - 2872 (2012/07/27)
A novel scalable stereoselective synthesis of 3α- and 3β-amino-5α-androstan-17-ones and 3α- and 3β-amino- 5α-pregnan-20-ones has been developed using phthalimide based Mitsunobu chemistry. In all four cases, the products were isolated as single diastereoisomers in high chemical yield and purity without the need for chromatography at any stage in their syntheses.
Effects of 3α-amino-5α-pregnan-20-one on GABAA receptor: Synthesis, activity and cytotoxicity
Matyas, Libor,Kasal, Alexander,Riera, Zoila Babot,Sunol, Cristina E.
, p. 1506 - 1516 (2007/10/03)
The 3α-hydroxy function has been considered essential for the biological activity of neurosteroids at the GABAA receptor. It was found that 3α-amino-5α-pregnan-20-one (3) increased the binding of [3H]flunitrazepam at the GABAA receptor in the primary culture of cortical neurons. This derivative did not display cytotoxicity at relevant neuroactive concentrations, and its structure enabled us to gain further insight into possible functional group modifications in position 3α. Various synthetic methods were investigated in search for the most suitable synthetic approach.
