Synthesis of 2,4-diketoacids and their aqueous solution structures

Abstract

The synthesis of several 2,4-diketo carboxylic acids by standard methods was undertaken to study the substrate speciÐcity of the carbon-carbon bond hydrolases. It was shown by 1Hand 13C-NMR experiments that compounds with 4-alkyl, 4-alkenyl and 4-alicyclic substituents exist in three main forms : 2,4-diketo, 2-enol-4-keto and 2-hydrate-4-keto. The equilibrium ratios of these aqueous solution structures were similar, but were markedly a †ected by the pH values (1.5È10.5). At pH 7.5 the ratio of these structures was approximately 4 : 5 : 1, but at low pH values the 2-hydrate predominated (B50%) and at high pH values the 2-enolate carboxylate was dominant (B80%) while the 2-hydrate was not detected. 4-Aryl substituents gave one pH-independent isomer formulated with C-2, C-3 and C-4 electrons delocalized in conjugation with the arene at C-4. This interpretation of a very rapid equilibrium between 2-and 4-enolate isomers to give a p-delocalized six-membered ring in conjugation with arene substituents is supported by the e †ect of divalent metal ions on the structural forms. Rate and equilibrium constants for several of these solution interconversions are inÑuenced by pH. Mg2`coordinates to the 2-enolate dianion of alkyl analogues, whereas Cu2`forms a six-membered p-delocalized ring with the 2-and 4-oxo atoms in conjugation with the arenes. Exchange of 2H from solvent occurs with the protons at C-3. The 2H 2 O-enriched dimers of the 4-alkyl analogues in aqua were characterized as a product of self-aldol condensations. These data have facilitated enzyme mechanism studies of CwC bond hydrolysases (b-ketolases).

An LFER study of the protolytic equilibria of 4-aryl-2,4-dioxobutanoic acids in aqueous solutions

“…(5)(6)(7)(8)(9)(10) are twofold standard deviations. 14 The coefficients following the terms in Eqs.…”

“…The reported compounds (1)(2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13) are inactive or exert low activity and are intended to be used to develop a model for a larger set incorporating active congeners. Acidity constants of the studied compounds in aqueous solutions have hitherto not been reported.…”

The Effect of Phenyl Substituents on 13C NMR Shifts and Metal Ions Binding to 4-Phenyl-2,4-Dioxobutanoic Acid Derivatives

“…Approximately nine percent comprise of -ketoenol moieties on "aliphatic" carbons and are classified as extremely inefficient with respect to intermolecular H-bonding, particularly toward hydrogen bond acceptors (O or N). Private communication with authors revealed additional data: only two structures [32,33] within studied set can strictly be compared with the derivatives reported in this article (1)(2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16), lacking >S=O as hydrogen bond donor. Furthermore, one structure [4- [34] that can be related to our set, having -SO 2 Me fragment on phenyl ring, shows the ketoenol contacts with >S=O group, making strong H-bonding O-H···O=S.…”

“…Compounds having core structure Ph-C(O)-CH 2 -C(O)-COOH can exist in two enolic forms (probably locked by intramolecular H-bonding) and one flexible diketo form (due to presence of two rotatable bonds) [15]. It is proposed that -diketo moiety functionally sequestrate divalent metal ions, critical cofactors at the enzyme catalytic core, while the enolic forms act by ligation of one metal ion and simultaneous H-bonding to catalytic core amino acid residues [8].…”

Colorimetric Fluoride‐Anion Sensor Based on Intramolecular Hydrogen Bonding and Enol–Keto Tautomerization of a Phenothiazine Derivative

“…Our study proposes that this color is due to the enol -keto tautomerism of 1 [31]. -Compound 1 is not fluorescent, possibly due to the quenching effect of the carbonyl groups (nonemissive n !…”