4116-38-5Relevant academic research and scientific papers
Tautomerism of Orotic Acid Dianion. Effect of Calcium and Magnesium Cations on the Tautomeric Constant and on Tautomerization Dynamics
Dodin, Guy,Dubois, Jacques-Emile
, p. 3049 - 3056 (1980)
Orotic acid dianion (HL2-) exists in basic aqueous solutions as a mixture of two isomeric structures (KT = / = 0.4 +/- 0.08, ΔHT = -0.3 +/- 0.05 kcal, ΔST = -2 +/- 0.4 eu).Its tautomeric interconversion as investigated by T-jump relaxation is fast (τ never exceeds 30 μs in D2O) and is catalyzed by OD- OD- = (3.3 +/- 0.2) 108 M-1 s-1>, by D2O acting as an acid D2O = (3 +/- 0.3) 104 s-1> and by orotate monoanion H2L- = (4 +/- 0.7) 106 M-1 s-1>.The orientation of orotic acid methylation is discussed in terms of the change in tautomer populations caused by temperature.The tautomeric equilibrium constant is markedly affected by alkaline earth cations (Ca2+ and Mg2+) owing to a specific complexation of the N(3)H form.Estimates of the complex formation constants, Kcomp, are (1.7 +/- 0.2) 102 and (5 +/- 0.5) 102 M-1 for Ca2+ and Mg2+, respectively.The relaxation time for the complexation process is shorter than 1 μs for Ca2+, whereas it is in the millisecond range for Mg2+ with a second order rate constant equal to (5.5 +/- 0.6) 105 M-1 s-1.
Substituent Effects in Non-Aromatic Nitrogen Heterocycles: Alkaline Hydrolysis of Methyl N-Methyl(oxo)dihydropyridinecarboxylates and Diaza Analogues
Deady, Leslie W.
, p. 637 - 641 (2007/10/02)
Ester hydrolysis studies on some isomeric methoxycarbonyl derivatives of N-methylpyridin-2- and 4-ones show that reaction rates are affected by the relative positions of CO2Me, =O and NMe functions in ways which could not be predicted.However, from limited results for analogous pyrimidine derivatives, it seems that reactivity in these polyfunctional compounds can be predicted from the pyridine data by assuming additivity of effects.
Model Chemistry for a Covalent Mechanism of Action of Orotidine 5'-Phosphate Decarboxylase
Silverman, Richard B.,Groziak, Michael P.
, p. 6434 - 6439 (2007/10/02)
Orotidine 5'-phosphate decarboxylase (ODase) catalyzes the conversion of orotidylate to uridylate, the last step in the de novo biosynthesis of pyrimidine nucleotides.Model reactions are described that support a covalent catalytic mechanism for this enzyme in which, following protonation of the carboxyl group of orotidylic acid, an active-site nucleophile undergoes a Michael addition to the C-5 position.This covalent complex breaks down via an acid-base-catalyzed decarboxylative elimination reaction to give uridylate and CO2 (Scheme II).The enzyme mechanism is modeled in two parts, the Michael addition reaction and the decarboxylative elimination.Bisulfite is shown to undergo a Michael addition to N,N-dimethylorotaldehyde and at room temperature to N,N-dimethyl-6-acetyluracil, both models for the activated form of orotidylate, the substrate for ODase (6 -> 7).In a separate study, (+/-)-1,3-dimethyl-r-5-(methylthio)-5-methyl-trans-6-carboxyl-5,6-dihydrouracil (15) was prepared as a model for the ODase-orotidylate covalent complex.Activation by methylation of the sulfide (as a model for enzyme-catalyzed protonation) leads to instantaneous decarboxylative elimination at room temperature.When the corresponding ester (9c) is methylated, the dimethylsulfonium salt (16b) can be isolated, which upon ester hydrolysis gives the decarboxylative elimination product.These model studies support the Michael addition-decarboxylative elimination mechanism in favor of a noncovalent mechanism previously reported (Beak, P.; Siegel, B.J.Am.Chem.Soc. 1976, 98, 3601).
