180902-61-8Relevant academic research and scientific papers
Syntheses and kinetic evaluation of racemic and optically active 2-benzyl-2-methyl-3,4-epoxybutanoic acids as irreversible inactivators for carboxypeptidase A
Lee, Mijoon,Kim, Dong H.
, p. 913 - 922 (2007/10/03)
Racemic and optically active 2-benzyl-2-methyl-3,4-epoxybutanoic acids were synthesized and evaluated as inactivators for carboxypeptidase A, a representative zinc-containing proteolytic enzyme. Only the threo-form of the inactivator is effective and its potency in terms of kinact/KI value is lower by 42-fold compared with 2-benzyl-3,4-epoxybutanoic acid, indicating that the α-methyl group affects adversely in the inactivation contrary to the expectation that it would enhance the inactivation activity of the inhibitor through additional interactions of the methyl group with a small cavity (α-methyl hole) present next to the S1′ hydrophobic pocket. Of the enantiomeric pair, the inactivator having the (2S,3R)-configuration is more potent than its enantiomer by 44-fold. The observed kinetic results may be rationalized on the basis that the methyl group in the inactivator having the (2R,3S)-configuration experiences the van der Waals repulsive interactions with the bottom of the active site crevice in binding to CPA, casting a doubt on the presence of the so-called α-methyl hole at the active site of carboxypeptidase A. Copyright
Regiocontrol in alkylation of lithium dienediolates of unsaturated carboxylic acids
Brun,Gil,Parra
, p. 156 - 159 (2007/10/03)
Alkylation of dienediolates from unsaturated carboxylic acids with benzylic halides often results in mixtures of regioisomers. However it can be controlled by adequate modification of the reaction conditions. Thus, addition of DMI leads mainly to the α-re
Alkylation of lithium dienediolates of butenoic acids. Regioselectivity effects of structure and leaving group of the alkylating agent
Aurell, Maria J.,Gil, Salvador,Mestres, Ramon,Parra, Margarita,Parra, Lilian
, p. 4357 - 4366 (2007/10/03)
Regioselectivity of alkylation of but-2-enoic acids I and 2 by alkyl halides strongly depends on the reactivity of the electrophile. High α selectivity results for saturated alkyl halides, whereas poor α-selectivity is obtained for highly reactive allyl and benzyl halides. For reactive alkylating halides selectivity is partly governed by the ion pairing aggregates of the dienediolates. Lithium bromide and the carboxylate generated in the ongoing reaction cause opposite effects on regioselectivity.
New conditions for the generation of dianions of carboxylic acids
Brun, Eva M.,Casades, Isabel,Gil, Salvador,Mestres, Ramon,Parra, Margarita
, p. 5443 - 5446 (2007/10/03)
Lithium carboxylic acid enediolates are generated efficiently using lithium amides prepared from thienyllithium or butyllithium and either diethylamine, piperazine, N,N'-dibenzylethylenediamine, N-benzylpiperazine or 1,3,3-trimethyl-6-azabicyclo[3.2.1]oct
