Thiouracil, reduction

Thiouracils Reduction Reduced catabolism of vitamin K-dependent clotting factors Adjust dosage... 

Botta and coworkers recently developed an Oxone cleavage methodology for the solid-phase synthesis of substituted uracils (equation 57)165. Whereas some common methods of thioether cleavage, such as reduction with Na/NH3, acid catalyzed hydrolysis, heavy metal ions followed by treatment with hydrogen sulfide and iodotrimethylsilane proved to be unsuccessful for this reduction, Oxone was shown to be an efficient and selective reagent for cleavage of polymer bound thiouracils. 

Some data suggested that a transient covalent linkage of tRNA to the synthetases may form through addition of a nucleophilic group of the enzyme to the 6 position of the uracil (or 4-thiouracil) present in position 8 of all tRNAs (Eq. 19-3).257 The two isoacceptors tRNATyr species in E. coli contain 4-thiouracil at this position. The C=C bond in this base can be saturated by sodium borohydride reduction, which was found not only to prevent the covalent interaction with the enzyme but also to prevent aminoacylation of the tRNA. However, Eq. 29-3 probably describes a side reaction irrelevant to tRNA function. 

Scheme 17. Proposed pathways for the electrochemical reduction of 4-thiouracil...

As might have been anticipated from the behaviour of 2-thiouracil (see above), 2,4-dithiouracil exhibits polarographic behaviour similar to that for 4-thiouracilI40). In the pH range 3-11 it gives three waves, the first two of which are due to the catalytic activity of dithiouracil, and the third to the catalytic activity of the reduction product(s) formed at the potential of wave II. As for 4-thiouracil, wave II overlaps the electro-... 

In thiouracil and other 2-pyrimidinethiones the reduction takes place in the hetero ring rather than at the thione [475]. 

Reduction of [IrCls] by a variety of agents has been cited. The reduction of [IrXs] " (Cl, Br) by 2-thiouracil and 2-thiopyrimidine follows second-order rate laws, first-order with respect to both the concentration of the oxidant and the reductant. A pH-rate profile as well as activation parameters have been presented, and a free radical mechanism proposed." Reduction in aqueous alcoholic solution by aquated electrons, hydrogen and alkyl radicals was investigated by pulse radiolysis, and found to result in the production of [IrClg] " A kinetic examination of reaction (123) in aqueous solution shows that this outer-sphere electron transfer reaction proceeds by parallel paths first and second order in substrate (SCN ). The kinetics of the oxidation of hydrazine by [Ir(Cl)4(H20)2], [Ir(Cl)5(H20)], [IrClef , as well as [IrBrsf , in aqueous acidic perchlorate solution have been investigated." ... 

Thiouracil is a selective inhibitor of nNOS antagonising tetrahydropteridin-dependent enzyme activation and dimerisation (Palumbo et al. 2000). It caused a 60 % inhibition of H2O2 production in the absence of L-arginine and tetrahydropteridin, and antagonised tetrahydropteridin-induced dimerisation of nNOS, but did not affect cytochrome c reduction. 

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