503-64-0Relevant academic research and scientific papers
Novel syn intramolecular pathway in base-catalyzed 1,2-elimination reactions of β-acetoxy esters
Mohrig, Jerry R.,Carlson, Hans K.,Coughlin, Jane M.,Hofmeister, Gretchen E.,McMartin, Lea A.,Rowley, Elizabeth G.,Trimmer, Elizabeth E.,Wild, Andrew J.,Schultz, Steve C.
, p. 793 - 798 (2007)
(Chemical Equation Presented) As part of a comprehensive investigation of electronic effects on the stereochemistry of base-catalyzed 1,2-elimination reactions, we observed a new syn intramolecular pathway in the elimination of acetic acid from β-acetoxy esters and thioesters. 1H and 2H NMR investigation of reactions using stereospecifically labeled tert-butyl (2R*,3R*)-3-acetoxy-2,3-2H2- butanoate (1) and its (2R*,3S*) diastereomer (2) shows that 23 ± 2% syn elimination occurs. The elimination reactions were catalyzed with KOH or (CH3)4-NOH in ethanol/water under rigorously non-ion-pairing conditions. By contrast, the more sterically hindered β-trimethylacetoxy ester produces only 6 ± 1% syn elimination. These data strongly support an intramolecular (Ei) syn path for elimination of acetic acid, most likely through the oxyanion produced by nucleophilic attack at the carbonyl carbon of the β-acetoxy group. The analogous thioesters, S-tert-butyl (2R*,3R*)-3-acetoxy-2,3- 2H2-butanethioate (3) and its (2R*,3S*) diastereomer (4), showed 18 ± 2% syn elimination, whereas the β-trimethylacetoxy substrate gave 5 ± 1% syn elimination. The more acidic thioester substrates do not produce an increased amount of syn stereoselectivity even though their elimination reactions are at the Elcb interface.
Stereospecificity of the reaction catalyzed by enoyl-CoA hydratase
Wu, Wen-Jin,Feng, Yuguo,He, Xiang,Hofstein, Hilary A.,Raleigh, Daniel P.,Tonge, Peter J.
, p. 3987 - 3994 (2000)
Enoyl-CoA hydratase catalyzes the stereospecific hydration of α,β- unsaturated acyl-CoA thiolesters. Hydration of trans-2-crotonyl-CoA to 3(S)- hydroxybutyryl-CoA proceeds via the syn addition of water and thus the pro-2R proton of 3(S)-hydroxybutyryl-CoA is derived from solvent. Incubation of 3(S)-hydroxybutyryl-CoA with enzyme in D2O results in the slow exchange of the pro-2S proton with solvent deuterium, in addition to the anticipated rapid exchange of the pro-2R proton. Further experiments have shown that the exchange of the pro-2S proton occurs in concert with the formation of the incorrect 3(R)-hydroxybutyryl-CoA enantiomer. The rate of 3(R)- hydroxybutyryl-CoA formation is 4 x 105-fold slower than the normal hydration reaction, but at least 1.6 x 106-fold faster than the non-enzyme- catalyzed reaction. This has allowed us to determine that the absolute stereospecificity for the enzyme-catalyzed reaction is 1 in 4 x 105. The initial formation of 3(R)-hydroxybutyryl-CoA is hypothesized to occur via the incorrect hydration of trans-2-crotonyl-CoA. Once formed, the 3(R)- hydroxybutyryl-CoA dehydrates to give cis-2-crotonyl-CoA. While the equilibrium constant for the hydration of trans-2-crotonyl-CoA to 3(S)- hydroxybutyryl-CoA is 7.5, the equilibrium constant for the hydration of cis- 2-crotonyl-CoA to 3(R)-hydroxybutyryl-CoA is estimated to be ~1000. To validate this reaction scheme, cis-2-crotonyl-CoA has been synthesized and characterized. These studies demonstrate that the enzyme is capable of catalyzing the epimerization of hydroxybutyryl-CoA.
Vinylacidic Acid in the Reaction of Aza-Michael with 1-Ethylpyrazole
Arzumanyan, A. M.,Attaryan, H. S.,Danagulyan, G. G.,Khachatryan, H. N.,Shahkhatuni, A. G.
, p. 1488 - 1490 (2020/10/02)
Abstract: Commercial vinylacetic acid is a mixture of isomers of but-3-enoic andbut-2-enoic acids. It was shown that but-3-enoic acid undergoes isomerization inthe presence of a catalytic amount of 1-ethylpyrazole. The resulting Z- and E-isomersof but-2-enoic acid enter the aza-Michael reaction with pyrazole. The1H NMR analysis showed that by the end of theexperiment the ratio of unreacted Z- andE-isomers of but-2-enoic acid in thereaction mixture decreased by half (to 3 : 1), which pointed to a higherreactivity of the Z-isomer.
Dienolates of Cycloalkenones and α,β-Unsaturated Esters Form Diels–Alder Adducts by a Michael/Michael-Tandem Reaction Rather Than in One Step
Loesche, Ann-Christine,Brückner, Reinhard
supporting information, p. 562 - 573 (2018/12/11)
α,β-Unsaturated esters and lithium 1,3-dien-2-olates are known to furnish bicyclic lithium enolates by anionic Diels–Alder reactions. However, in principle, the respective products might form not only in a single step but also in two consecutive – or “tandem” – Michael additions, the first of which occurs intermolecularly, the second intramolecularly. Three cyclic lithium dienolates and four esters with a stereogenic Cα=Cβ bond reacted to give Diels–Alder adducts (10 times) or failed to react (2 times). Seven of the reactive combinations furnished adducts wherein the configuration of the former ester moiety had in part inverted. This precludes concerted pathways as their origins. This was a surprise since donors at C-2 of the 1,3-diene accelerate normal electron-demand Diels–Alder reactions in the order alkyl ⊕O? being a far better donor still, it is not obvious why the mechanism is non-concerted rather than concerted (and still more asynchronous).
Ru-Based Catechothiolate Complexes Bearing an Unsaturated NHC Ligand: Effective Cross-Metathesis Catalysts for Synthesis of (Z)-α,β-Unsaturated Esters, Carboxylic Acids, and Primary, Secondary, and Weinreb Amides
Liu, Zhenxing,Xu, Chaofan,Del Pozo, Juan,Torker, Sebastian,Hoveyda, Amir H.
supporting information, p. 7137 - 7146 (2019/05/10)
Despite notable progress, olefin metathesis methods for preparation of (Z)-α,β-unsaturated carbonyl compounds, applicable to the synthesis of a large variety of bioactive molecules, remain scarce. Especially desirable are transformations that can be promoted by ruthenium-based catalysts, as such entities would allow direct access to carboxylic esters and amides, or acids (in contrast to molybdenum-or tungsten-based alkylidenes). Here, we detail how, based on the mechanistic insight obtained through computational and experimental studies, a readily accessible ruthenium catechothiolate complex was found that may be used to generate many α,β-unsaturated carbonyl compounds in up to 81% yield and ≥98:2 Z/E ratio. We show that through the use of a complex bearing an unsaturated N-heterocyclic carbene (NHC) ligand, for the first time, products derived from the more electron-deficient esters, acids, and Weinreb amides (vs primary or secondary amides) can be synthesized efficiently and with high stereochemical control. The importance of the new advance to synthesis of bioactive compounds is illustrated through two representative applications: An eight-step, 15% overall yield, and completely Z-selective route leading to an intermediate that may be used in synthesis of stagonolide E (vs 11 steps, 4% overall yield and 91% Z, previously), and a five-step, 25% overall yield sequence to access a precursor to dihydrocompactin (vs 13 steps and 5% overall yield, formerly).
INHIBITORS OF BRUTON'S TYROSINE KINASE AND METHODS OF THEIR USE
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Page/Page column 263, (2018/06/30)
Compounds of formula (I') and methods of their use and preparation, as well as compositions comprising compounds of formula (I').
INHIBITORS OF BRUTON'S TYROSINE KINASE AND METHODS OF THEIR USE
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Page/Page column 263, (2017/09/02)
The present disclosure is directed to compounds of formula I and methods of their use and preparation, as well as compositions comprising compounds of formula I.
Anticancer platinum complexes as non-innocent compounds for catalysis in aqueous media
Aleman, Jose,Del Solar, Virginia,Navarro-Ranninger, Carmen
supporting information; experimental part, p. 454 - 456 (2010/04/30)
An efficient cyclization of alkyne-acids to enol-lactones catalyzed by anticancer platinum(ii) and platinum(iv) compounds is described. These compounds are not only DNA-binding complexes; they can also catalyze reactions in solvents such as acetone, methanol, water or blood plasma.
New reactions of anticancer-platinum complexes and their intriguing behaviour under various experimental conditions
Aleman, Jose,Del Solar, Virginia,Cubo, Leticia,Quiroga, Adoracion G.,Navarro Ranninger, Carmen
scheme or table, p. 10601 - 10607 (2011/01/05)
The anticancer platinum complexes here described react with organic substrates (such as acids, alkenes, alkynes) and catalyze transformations that can occur in biomolecules which contain unsaturated functions. We have analyzed the role of the platinum complexes in the observed reactions and studied the progress of the detected transformations upon variation of the reaction conditions. The Royal Society of Chemistry 2010.
The detection of PHIP effects allows new insights into the mechanism of olefin isomerisation during catalytic hydrogenation
Viale, Alessandra,Santelia, Daniela,Napolitano, Roberta,Gobetto, Roberto,Dastru, Walter,Aime, Silvio
experimental part, p. 4348 - 4351 (2009/02/08)
PHIP (parahydrogen-induced polarisation) effects in the 1H NMR spectra of the products of Rh-complex-catalysed alkyne hydrogenation brings to light the fact that the cis-trans isomerisation of the formed olefin occurs through the formation of a σ-bonded intermediate stabilised by the reversible addition of a hydrogen molecule at the metal centre. Wiley-VCH Verlag GmbH & Co. KGaA, 2008.
