75717-07-6Relevant 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
Selective γ- Alkylation of Copper Enolates Derived from α,β-Unsaturated Acids: Factors Affecting Scope and Regio- and Stereoselectivity
Savu, Patricia M.,Katzenellenbogen, John A.
, p. 239 - 250 (2007/10/02)
Copper dienolates derived from α,β-unsaturated acids undergo alkylation at the γ-carbon with high regioselectivity.A systematic investigation has been made of several factors that affect the γ-alkylation process of the dienolate derived tiglic acid (1): alterations in the nature of the counterion, in the stoichiometry of cuprous ion, and in the nature of the electrophile.Compared to allylic electrophiles, nonallylic electrophiles react with copper dienolates sluggishly and with little selectivity for the γ-carbon; vinylic epoxides, however, are particularly goodalkylating agents.They undergo allylic transposition and react at the γ-carbon of the dienolate with high selectivity (70-90 percent), generating an allylic unit that forms part of a 1,5-diene skeleton oxygenated at both ends.Tiglic (1) and crotonic (3) acids react with vinylic epoxides to form a 1,5-diene with entirely E stereochemistry at the 2,3 double bond, while senecioic acid (2) forms a 1,5-diene with mostly Z stereochemistry at the 2,3 double bond.Geometry at the 6,7 double bond depends both on the α,β-unsaturated acid used and on the structure of the epoxide.With allylic electrophiles under direct (SN2) attack, stereochemical analysis showed that some isomerization occurs around the 6,7 double bond (derived from the electrophile).Addition of cuprous ion to the lithium dianion of 2-hexenoic acid (17) was found to enhance the regioselectivity of γ alkylation, but a subsequent Michael addition reaction limits the potential of γ alkylation in this system.
