15568-87-3Relevant academic research and scientific papers
Synthesis of Densely Functionalized N-Alkenyl 2-Pyridones via Benzyne-Induced Ring Opening of Thiazolino-Fused 2-Pyridones
Singh, Pardeep,Cairns, Andrew G.,Adolfsson, Dan E.,?dén, J?rgen,Sauer, Uwe H.,Almqvist, Fredrik
, p. 6946 - 6950 (2019)
We report the synthesis of 6-arylthio-substituted-N-alkenyl 2-pyridones by ring opening of bicyclic thiazolino-2-pyridones with arynes. Varied functionalization was used to investigate scope and substituent influences on reactivity. Selected conditions favor thioether ring opening over [4 + 2] cycloaddition and an unusual aryne incorporating ring expansion. Deuterium labeling was used to clarify observed reactivity. Using the knowledge, we produced drug-like molecules with complex substitution patterns and show how thioether ring opening can be used on scaffolds with competing reactivities.
Pyridine-Fused 2-Pyridones via Povarov and A3 Reactions: Rapid Generation of Highly Functionalized Tricyclic Heterocycles Capable of Amyloid Fibril Binding
Singh, Pardeep,Adolfsson, Dan E.,?dén, J?rgen,Cairns, Andrew G.,Bartens, Christian,Br?nnstr?m, Kristoffer,Olofsson, Anders,Almqvist, Fredrik
, p. 3887 - 3903 (2019)
We here describe the use of three-component reactions to synthesize tricyclic pyridine ring-fused 2-pyridones. The developed protocols have a wide substrate scope and allow for the installation of diverse chemical functionalities on the tricyclic central fragment. Several of these pyridine-fused rigid polyheterocycles are shown to bind to Aβ and α-synuclein fibrils, which are associated with neurodegenerative diseases.
FLUOROMALONYL HALFTHIOESTERS
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Page/Page column 20, (2016/06/06)
The present invention relates to Fluoromalonyl Halfthioesters (F-MAHTs) of formula (I), wherein R1 represents hydrogen, halogen, an optionally substituted alkyl group, an optionally substituted cycloalkyl group, an optionally substituted aryl g
Investigation on the chemoenzymatic synthesis of threo- and erythro-β-hydroxy-L-glutamic acid derivatives
Sagui, Francesca,De Micheli, Carlo,Roda, Gabriella,Magrone, Pietro,Pizzoli, Rachele,Riva, Sergio
experimental part, p. 27 - 34 (2012/04/10)
A derivative of the malonic semialdehyde was transformed by means of a bioconversion catalyzed by the enzyme L-threonine aldolase from E. coli into a 6:4 epimeric mixture of two precursors of β-hydroxy glutamic acid. The enzyme was selective for the formation of the (S)-configuration at C-2, whereas the configuration at C-3 was not controlled. The two epimers were separated exploiting a diastereoselective acylation in organic solvent catalyzed by lipase PS. The relative and absolute configurations of the products were preliminarily assigned on the base of the model proposed by Kazslauskas for the stereopreference of lipase PS and by comparison of the chemical shifts of the H-2 and H-3 protons of the two homologues. The possibility of transforming the obtained products into β-hydroxy glutamic acid derivatives by conventional chemical reactions was demonstrated.
Synthetic routes to pyrrolizine-1,5-dione derivatives by flash vacuum pyrolysis of amidomethylene derivatives of Meldrum's acid
McNab, Hamish,Morrow, Mark,Parsons, Simon,Shannon, David A.,Withell, Kirsti
supporting information; experimental part, p. 4936 - 4942 (2010/02/16)
Methoxymethylene Meldrum's acid 1 reacts with 5- and 6-membered lactams in refluxing acetonitrile to give the N-substituted products 9-15. If the reactions are continued for extended times, the Meldrum's acid derivatives decompose to provide enamidoesters
Hydrolysis of α-alkyl-α-(methylthio)methylene Meldrum's acids. A kinetic and computational investigation of steric effects
Bernasconi, Claude F.,Brown, Shoshana D.,Ali, Mahammad,Rappoport, Zvi,Yamataka, Hiroshi,Salim, Hatim
, p. 4795 - 4802 (2007/10/03)
The rates of hydrolysis of α-R-α-(methylthio)methylene Meldrum's acids (8-R with R = H, Me, Et, s-Bu, and t-Bu) were determined in basic and acidic solution in 50% DMSO-50% water (v/v) at 20 °C. In basic solution (KOH), nucleophilic attack to form a tetrahedral intermediate (T OH-) is rate limiting for all substrates (κ1OH). In acidic solution (HCl) and at intermediate pH values (acetate buffers), water attack (κ1H2O) is rate limiting for 8-Me, 8-Et, and 8-t-Bu; the same is presumably the case for 8-t-Bu, but rates were too slow for accurate measurements at low pH. For 8-H, water attack is rate limiting at intermediate pH but at pH OH- to products, two of which being unique to hydrolysis reactions and taking advantage of the acidic nature of the OH group in TOH-. This scheme provides an explanation why even at high [KOH] TOH- does not accumulate to detectable levels even though the equilibrium for OH - addition to 8-R is expected to favor TOH, and why at low pH water attack is rate limiting for R = Me, Et, s-Bu, and t-Bu but leaving group departure becomes rate limiting with the sterically small R = H. The trend in the k1OH and k1H2O indicates increasing steric crowding at the transition state with increasing size of R, but this effect is partially offset by a sterically induced twisting of the C=C double bond in 8-R which leads to its elongation and makes the substrate less stable and hence more reactive. Our computational results suggest that this effect becomes particularly pronounced for R = t-Bu and explains why k 1OH for 8-t-Bu is somewhat higher than for the less crowded 8-s-Bu.
