503-64-0Relevant articles and documents
Hocking
, p. 482 (1971)
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.
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).
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').
