51631-45-9Relevant academic research and scientific papers
Forming All-Carbon Quaternary Stereocenters by Organocatalytic Aminomethylation: Concise Access to β2,2-Amino Acids
Shao, Ying,Sun, Jiangtao,Tang, Shengbiao,Wang, Kai,Yu, Jianliang
supporting information, p. 23516 - 23520 (2020/10/21)
The asymmetric synthesis of β2,2-amino acids remains a formidable challenge in organic synthesis. Here a novel organocatalytic enantioselective aminomethylation of ketenes with stable and readily available N,O-acetals is reported, providing β2,2-amino esters bearing an all-carbon quaternary stereogenic center in high enantiomeric ratios with a catalytic amount of chiral phosphoric acid. Typically, this transformation probably proceeds through an asymmetric counter-anion-directed catalysis. As a result, a concise, practical, and atom-economic protocol toward rapidly access to β2,2-amino acids has been developed.
Stereo- and Chemodivergent NHC-Promoted Functionalisation of Arylalkylketenes with Chloral
Douglas, James J.,Churchill, Gwydion,Slawin, Alexandra M. Z.,Fox, David J.,Smith, Andrew D.
supporting information, p. 16354 - 16358 (2015/11/09)
Stereo- and chemodivergent enantioselective reaction pathways are observed upon treatment of alkylarylketenes and trichloroacetaldehyde (chloral) with N-heterocyclic carbenes, giving selectively either β-lactones (up to 88:12 dr, up to 94% ee) or α-chloroesters (up to 94% ee). Either 2-arylsubstitution or an α-branched iPr alkyl substituent within the ketene favours the chlorination pathway, allowing chloral to be used as an electrophilic chlorinating reagent in asymmetric catalysis.
Competitive activity-based protein profiling identifies Aza-β-lactams as a versatile chemotype for serine hydrolase inhibition
Zuhl, Andrea M.,Mohr, Justin T.,Bachovchin, Daniel A.,Niessen, Sherry,Hsu, Ku-Lung,Berlin, Jacob M.,Dochnahl, Maximilian,Lopez-Alberca, Maria P.,Fu, Gregory C.,Cravatt, Benjamin F.
, p. 5068 - 5071 (2012/05/05)
Serine hydrolases are one of the largest and most diverse enzyme classes in Nature. Most serine hydrolases lack selective inhibitors, which are valuable probes for assigning functions to these enzymes. We recently discovered a set of aza-β-lactams (ABLs) that act as potent and selective inhibitors of the mammalian serine hydrolase protein-phosphatase methylesterase-1 (PME-1). The ABLs inactivate PME-1 by covalent acylation of the enzyme's serine nucleophile, suggesting that they could offer a general scaffold for serine hydrolase inhibitor discovery. Here, we have tested this hypothesis by screening ABLs more broadly against cell and tissue proteomes by competitive activity-based protein profiling (ABPP), leading to the discovery of lead inhibitors for several serine hydrolases, including the uncharacterized enzyme α,β-hydrolase domain-containing 10 (ABHD10). ABPP-guided medicinal chemistry yielded a compound ABL303 that potently (IC50-30 nM) and selectively inactivated ABHD10 in vitro and in living cells. A comparison of optimized inhibitors for PME-1 and ABHD10 indicates that modest structural changes that alter steric bulk can tailor the ABL to selectively react with distinct, distantly related serine hydrolases. Our findings, taken together, designate the ABL as a versatile reactive group for creating first-in-class serine hydrolase inhibitors.
N-heterocyclic carbene-mediated enantioselective addition of phenols to unsymmetrical alkylarylketenes
Concellon, Carmen,Duguet, Nicolas,Smith, Andrew D.
supporting information; experimental part, p. 3001 - 3009 (2010/03/26)
Chiral N-heterocyclic carbenes (NHCs) mediate the enantioselective addition of 2-phenylphenol to unsymmetrical alkylarylketenes, delivering α-alkyl-α-arylacetic acid derivatives with good levels of enantiocontrol (up to 84% ee). Enantiodivergent stereochemical outcomes are observed using 2-phe-nylphenol and benzhydrol in the NHC-promoted esterification reaction using a triazolium precatalyst derived from pyroglutamic acid, consistent with distinct mechanistic pathways operating within these processes.
Asymmetric dimerization of disubstituted ketenes catalyzed by N-heterocyclic carbenes
Lv, Hui,Zhang, Yan-Rong,Huang, Xue-Liang,Ye, Song
supporting information; experimental part, p. 2715 - 2718 (2009/10/20)
A series of chiral N-heterocyclic carbenes (NHCs), derived from L-pyrogutamic acid, were found to be efficient catalysts for the asymmetric dimerization of alkylarylketenes to give the corresponding α-quaternary β-alkylidenyl-β-lactones in good yields with up to 97% ee. A chiral NHC with a proximal hydroxy group is superior in comparison with the corresponding NHC with its hydroxy group protected.
