2-Thiouracils uracils

The best direct synthetic route to uracil is probably the classical procedure from malic acid and urea in concentrated sulfuric acid (26JA2379), despite efforts to use maleic acid, urea and polyphosphoric acid (71S154) or propiolic acid, urea and a little concentrated sulfuric acid (77JOC2185) to achieve the same result. However, the most convenient source (apart from purchase) is to convert 2-thiouracil (937 X = S) into uracil by boiling with aqueous chloroacetic acid (52MI21300) or perhaps by oxidation with DMSO in strong sulfuric acid (74S491). 

A) Preparation of 1-(2,3,5-Tri-0-Acetyl- -D-Arat>inofuranosy/)-4-Thiouracil A mixture of 1.85 g (5.0 mmol) of 1-(2,3,5-tri-0-acetyl-(3-arabinofuranosyl)uracil, 1.23 g (5.55 mmol) of phosphorus pentasulfide, and 30 ml of pyridine was heated under gentle reflux for 2.5 hours with exclusion of moisture. The reaction mixture was cooled, and the supernatant solution was transferred by means of a pipette into a mixture of crushed ice and water. 

Fig. 4.7 The reaction of cyanoacetaldehyde with thiourea gives 2-thiocytosine, which can react further to give cytosine or thiouracil (and further to uracil) (Robertson et al., 1996)...

Finally, the most complex synthetic reaction clearly catalysed by RNA molecules generated by in vitro selection is the formation of the C-N bond of a nucleoside (Scheme 7), from 4-thiouracil and most of the natural substrate for the natural (uracil phos-phoribotransferase) reaction.1461. (Thiouracil was used because it is easily tagged by alkylation on sulfur.) The catalytic RNAs produced by 11 rounds of selection required Mg++ cations and had kcat as high as 0.13 min-1,with kcaJKM at least 107 times greater than the (undetectable) uncatalyzed reaction. Once again these systems are convincing, rather efficient enzyme mimics. 

The thermal ring closure of isopropylidene N-[amino(thio)carbonyl]ami-nomethylenemalonates (439, X = O, S) in boiling diphenyl ether for 5 min afforded uracil and thiouracil (1193, X = O, S) in 68% and 70% yields, respectively (84SC96I). 

The reaction of 113 with urea and thiourea (both compounds are weaker bases than guanidine) requires the presence of sodium ethoxide. With urea, uracil and with the thiourea, 2-thiouracil are obtained, respectively. 

Among the dihydro analogues of thiouracil, 2-mercapto-6-methyl-5,6-dihydro-uracil (LXXX) retains some of the antithyroid activity exhibited by 2-thiouracils [642] (see Part 1 of this review. Volume 6). This compound can be obtained either by the condensation of thiourea with ethyl crotonate or by the hydrogenation of 2-mercapto-6-methyluracil. 

Reaction of 6-amino-uracil or thiouracil with an arylidene-substituted Meldrum s acid in boiling AcOH afforded the corresponding octahydropyrido[2,3-r/ pyrimidines 506 <1996JHC45>. Similar cyclization using 6-amino-2-meth-oxy or methylthiopyrimidin-4-one derivatives in boiling nitrobenzene led to 507 <1997JHC521>. 

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. 

Pd/tppts-catalysed allylations of aromatic amines (Equation 13) and phenols49,534 or uracils and 2-thiouracils.535... 

The 5,6-double bond in uracil, 5-fluorouracil, /V-alkyluracils, thiouracils, and uridines adds sodium sulfite or bisulfite to give the corresponding 5,6-dihydro-6-sulfonic acid salts. Bisulfite addition to cytosines and cytidine may be succeeded by a second reaction involving nucleophilic replacement of the amino group, for example, by water. 

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. 

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