Synthesis of Compounds Related to Thymine. I. 5-Mercaptouracil and Some S-Substituted Derivatives

Synthesis of 5-(Carboranylalkylmercapto)-2‘-deoxyuridines and 3-(Carboranylalkyl)thymidines and Their Evaluation as Substrates for Human Thymidine Kinases 1 and 2

“…S-Alkylation of 5-mercaptouracil ( 11 ) was accomplished under argon and in deoxygenated methanol to prevent the oxidation of 11 during the reaction (Scheme ). 5-Mercaptouracil 31 ( 11 ) was alkylated with carboranyl tosylates 6 − 8 and 10 to yield the 5-S-alkylated mercaptouracils 12 − 15 using only 1 equiv of sodium methoxide to avoid the possible alkoxide degradation of the carboranes …”

The Effect of Added Sodium or Potassium Chloride upon the α-Chymotrypsin Catalyzed Hydrolysis of Chloroacetyl-L-tyrosinamide in Aqueous Solutions at 25° and pH 7.751

“…As before the primary data were evaluated by the method of Jennings and Nie-mann10 and the corrected initial velocities so obtained are given in Table II. When these found values of ro are compared with the values of yg which were calculated by means of equation (1) from the corresponding values of y §, which in turn were calculated from the previously determined values of Ks and &34•7 and the other known parameters of the system under investigation it will be seen that the two sets of values of Vo are in good agreement. Thus, we may conclude that the relation given by equation 1 is independent of the concentration of the specific substrate, at least for the particular uncharged specific substrate that was used in these studies and over the range of concentrations that were employed.…”

“…If hydrogen bonding plays an important role in the breakdown of the enzyme-substrate into products, the following may be suggested: (1) hydrogen bonding to the enzyme "surface" is not important since the complex has already formed by the time hydrogen bonding becomes important; (2) hydrogen bonding to a molecule of water may be important; (3) the water molecule appears in the enzymatic hydrolysis not as a part of the enzyme-substrate complex but as a reactant in the subsequent decomposition of the complex into products. The last conclusion is not only a consequence of the above data but also of the concept of competitive inhibition and is confirmed by the lack of oxygen exchange with carboxylic acids which inhibit enzymatic hydrolysis.38 The specification of the role of the water molecule in enzymatic hydrolysis seems to have been largely ignored except by several workers who have included the water molecule in the enzyme-substrate complex.34•35…”

“…In 1950 Jandorf3 noted that the addition of magnesium sulfate to systems containing a-chymotrypsin and acetyl-L-tyrosine ethyl ester led to a proportionality between the enzyme concentration and the so-called esterase activity which was not observed in the absence of added magnesium sulfate and that the addition of this salt in a sufficient but otherwise unspecified amount caused a fivefold increase in the apparent esterase activity of the enzyme over that observed in a control experiment where presumably a lesser amount of magnesium sulfate was present. However, this investigator also reported that "no salt which was found to potentiate the esterase activity of -chymotrypsin had an effect on the proteinase (casein hydrolysis) activity of the enzyme" thus leaving the impression, intended or not, that (1) Supported in part by a grant from Eli Lilly and Co.…”

Ring contractions of 5-diazouracils. I. Conversions of 5-diazouracils into 1,2,3-triazoles by hydrolysis and methanolysis

“…This had been suggested2 in the literature and a few reports of nucleophilic displacement reactions had been published. [3][4][5] Our preliminary studies, to determine the susceptibility of the diazo group of 05 -6(S)-cyclo-5-dia-zouridine1 (1) toward nucleophilic displacement, revealed that displacement reactions did not occur at low temperatures. In an effort to find a suitable solvent for conducting displacement reactions at elevated temperatures, we investigated the stability of 1 in acetonitrile at 100°.…”