85974-70-5Relevant academic research and scientific papers
Tandem Photoredox-Chiral Phosphoric Acid Catalyzed Radical-Radical Cross-Coupling for Enantioselective Synthesis of 3-Hydroxyoxindoles
Zhang, Yang,Ye, Dan,Shen, Lei,Liang, Kangjiang,Xia, Chengfeng
supporting information, p. 7112 - 7117 (2021/09/14)
A photochemical protocol that couples diarylamines and α-ketoesters to afford the chiral 3-hydroxyoxindoles through tandem photoredox and chiral phosphoric acid catalysis is developed. The reaction involves an enantioselective photochemical radical-radical cross-coupling process. The chiral phosphoric acid is discovered to play crucial roles by decreasing the reductive potentials of α-ketoesters and stereocontrolling the downstream asymmetric radical-radical cross-coupling via the formation of pentacoordinate complex.
Synthesis of 2-oxoglutarate derivatives and their evaluation as cosubstrates and inhibitors of human aspartate/asparagine-β-hydroxylase
Brewitz, Lennart,Nakashima, Yu,Schofield, Christopher J.
, p. 1327 - 1342 (2021/02/12)
2-Oxoglutarate (2OG) is involved in biological processes including oxidations catalyzed by 2OG oxygenases for which it is a cosubstrate. Eukaryotic 2OG oxygenases have roles in collagen biosynthesis, lipid metabolism, DNA/RNA modification, transcriptional regulation, and the hypoxic response. Aspartate/asparagine-β-hydroxylase (AspH) is a human 2OG oxygenase catalyzing post-translational hydroxylation of Asp/Asn-residues in epidermal growth factor-like domains (EGFDs) in the endoplasmic reticulum. AspH is of chemical interest, because its Fe(ii) cofactor is complexed by two rather than the typical three residues. AspH is upregulated in hypoxia and is a prognostic marker on the surface of cancer cells. We describe studies on how derivatives of its natural 2OG cosubstrate modulate AspH activity. An efficient synthesis of C3- and/or C4-substituted 2OG derivatives, proceedingviacyanosulfur ylid intermediates, is reported. Mass spectrometry-based AspH assays with >30 2OG derivatives reveal that some efficiently inhibit AspHviacompeting with 2OG as evidenced by crystallographic and solution analyses. Other 2OG derivatives can substitute for 2OG enabling substrate hydroxylation. The results show that subtle changes,e.g.methyl- to ethyl-substitution, can significantly alter the balance between catalysis and inhibition. 3-Methyl-2OG, a natural product present in human nutrition, was the most efficient alternative cosubstrate identified; crystallographic analyses reveal the binding mode of (R)-3-methyl-2OG and other 2OG derivatives to AspH and inform on the balance between turnover and inhibition. The results will enable the use of 2OG derivatives as mechanistic probes for other 2OG utilizing enzymes and suggest 2-oxoacids other than 2OG may be employed by some 2OG oxygenasesin vivo.
Copper catalyzed photoredox synthesis of α-keto esters, quinoxaline, and naphthoquinone: Controlled oxidation of terminal alkynes to glyoxals
Das, Deb Kumar,Kumar Pampana, V. Kishore,Hwang, Kuo Chu
, p. 7318 - 7326 (2018/10/15)
Herein, we report a facile visible light induced copper catalyzed controlled oxidation of terminal CC alkynes to α-keto esters and quinoxalines via formation of phenylglyoxals as stable intermediates, under mild conditions by using molecular O2 as a sustainable oxidant. The current copper catalysed photoredox method is simple, highly functional group compatible with a broad range of electron rich and electron poor aromatic alkynes as well as aliphatic alcohols (1°, 2° and 3° alcohols), providing an efficient route for the preparation of α-keto esters (43 examples), quinoxaline and naphthoquinone with higher yields than those in the literature reported thermal processes. Furthermore, the synthetic utility of the products has been demonstrated in the synthesis of two biologically active molecules, an E. coli DHPS inhibitor and CFTR activator, using the current photoredox process. In addition, we applied this methodology to the one-pot synthesis of a heterocyclic compound (quinoxaline, an FLT3 inhibitor) by trapping the intermediate phenylglyoxal with O-phenylenediamine. The intermediate phenylglyoxal can also be isolated and further reacted with an internal alkyne to form naphthoquinone. This process can be readily scaled up to the gram scale.
Construction of 1,2,5-tricarbonyl compounds using methyl cyanoacetate as a glyoxylate anion synthon combined with copper(I) iodide-catalyzed aerobic oxidation
Kim, Se Hee,Kim, Ko Hoon,Kim, Jae Nyoung
, p. 3335 - 3339 (2012/01/19)
A practical and efficient synthesis of various 1,2,5-tricarbonyl compounds is described. The synthesis has been carried out by a conjugate addition of methyl cyanoacetate to the β-position of α,β-unsaturated carbonyl compounds and a subsequent copper(I) iodide-catalyzed aerobic oxidation. In addition, various α-aryl- and α-alkyl-α-keto esters have been synthesized using a similar approach. Copyright
