Uracil amination

Methyl acetoacetate (MAA) and ethyl acetoacetate (EAA) are the most widely used esters they are found ia the pharmaceutical, agricultural, and allied industries. Both esters are used extensively as amine protecting agents ia the manufacture of antibiotics and synthetic sweeteners (Dane Salts) (147). Principal outiets for MAA are the manufacture of the organophosphoms insecticide dia2inon [33341-5] (148,149) and the uracil herbicides bromacil [31440-9] and terbacil [5902-51-2] (150,151) (see Insect conztiol technology Herbicides). 

Pyrimidine and imidazole rings are particularly important in biological chemistry. Pyrimidine, for instance, is the parent ring system in cytosine, thymine, and uracil, three of the five heterocyclic amine bases found in nucleic acids An aromatic imidazole ring is present in histidine, one of the twenty amino acids found in proteins. 

The sugar component in RNA is ribose, and the sugar in DNA is 2 -deoxy-ribose. (The prefix 2 -deoxv indicates that oxygen is missing from the 2 position of ribose.) DNA contains four different amine bases, two substituted purines (adenine and guanine) and two substituted pyrimidines (cytosine and thymine). Adenine, guanine, and cytosine also occur in RNA, but thymine is replaced in RNA by a closely related pyrimidine base called uracil. 

Attached by a covalent bond to carbon atom 1 of the deoxyribose ring is an amine (and therefore a base), which may be adenine, A (22) guanine, G (23) cytosine, C (24) or thymine, T (25). In RNA, uracil, U (26), replaces thymine. The base bonds to carbon atom 1 of deoxyribose through the nitrogen of the —NH— group (printed in red) and the compound so formed is called a nucleoside. All nucleosides have a similar structure, which we can summarize as the shape shown in (27) the lens-shaped object represents the attached amine. 

Because activated 4-0-trimethylsilylated-2, 3, 5 -0-acyluridines such as 3 are also obtained as reactive intermediates in the Friedel-Crafts-catalyzed silyl-Hilbert-Johnson reaction [59, 59 a] of persilylated uracils or 6-azauracils such as 227 with sugars such as l-0-acetyl-2,3,5-tri-0-benzoyl-/9-D-ribofuranose 228 in the presence of SnCl4, treatment of the reactive intermediate 229 with a large excess of pyrrolidine neutralizes the SnCLi. used and aminates 229 to afford the protected 6-aza-cytidine 230, although in 57% yield only [49, 59] (Scheme 4.20). 

Silylation-aminations of a variety of other hydroxy-N-heterocycles, for example 4(lH)-pyridinone, 2(lH)-pyrimidone, uracil, 2(lH)-quinoline, and 9(10H)-acridone are described in the full paper, which was published in English [27]. 

Figure 1.45 Reaction of bisulfite with cytosine bases is an important route of derivatization. It can lead to uracil formation or, in the presence of an amine (or hydrazide) containing compound, transamination can occur, resulting in covalent modification.

Additionally, nucleic acid bases have been used in the dynamic assembly of mixed-metal, mixed-pyrimidine metallacalix[n]arenes [47]. In this approach, Lippert and coworkers investigated the dynamic assembly of metallacalixarenes based on platinum (Pt ), palladium (Pd°), uracil, and cytosine assemblies with mixed amines. These combinations form cyclic metallacalix[n]arenes structures with n = A and = 8. Of the metallacalix[4]arenes, compounds were formed with five, six, and eight bonded metals, and a variety of nucleobase coimecfivities (UCUC and UCCU). The dynamic nature of this assembly allows access to novel and structurally diverse set of nucleobase metallacalixarenes. 

The thiazin-2,6-diones 49 lose one molecule of COS in boiling dimethylformamide (DMF) to afford l-substituted-6-alkyl uracils 98 (Scheme 2) <2005RJC134,2003TL5279>. The same products are obtained when 5-acyl-4-hydroxy-3,6-dihydro-2//-l,3-thiazine-2,6-diones 61 are heated together with the corresponding primary amine in hoiling DMF. The dimeric compound 99 and the nitrophenyl hydroxylated example 100 are produced by the same route <2005RJC134>. 

In DNA the sugar molecule in the nucleotide is 2-deoxyribose, and in RNA it is ribose. The amine bases in DNA are adenine, thymine, cytosine, and guanine, symbolized by A, T, C, and G, respectively. RNA contains adenine, cytosine, and guanine, but thymine is replaced by the based uracil (Figure 16.16). The primary structure of nucleic acids is given by the sequence of the amine side chains starting from the phosphate end of the nucleotide. For example, a DNA sequence may be -T-A-A-G-C-T. 

The amine bases making up DNA and RNA. Thymine generally occurs only in DNA and uracil only in RNA. 

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

Pyrimidine-2,4(1//,3//)-dione (uracil) does not react with 7V-fluorobis(trifluoromethylsul-fonyl)amine (Id) at 22 C in acetic acid, probably due to its insolubility, but when heated at 45 CC for 12 hours it gives a difluorinated acetoxy derivative which could not be isolated.114 1,3-Dimethyluracil reacts with two equivalents of 1 d at 22 °C to give 6-acetoxy-5,5-difluoro-l, 3-dimethyl-5,6-dihydrouracil in 85% yield while with one equivalent of Id 5-fluoro-l, 3-dimethyl-uracil (mp 132-134°C) is also obtained.114... 

A common source of DNA damage is the spontaneous loss of the amine group on cytosine and the formation of an amide. This occurs at a rate of about 100 times a day. Fortunately, the body produces enzymes able to detect and repair such degraded cytosines. Given this information, suggest why DNA differs from RNA in possessing the nucleotide thymine rather than uracil. 

The 15N magnetic resonance studies of the pyrimidine bases or their derivatives are scarce. Roberts et al.BB have measured the 1H and 15N magnetic resonance spectra of a number of pyrimidines including uracil and 1-methylcytosine. The most important result of this study was the elucidation of the dominant tautomeric structures of uracil and proto-nated 1-methylcytosine as the diketo, 32, and keto-amine form, 7, respectively (cf. Sections II and IV and the spectrum of 1-methylcytosine hydrochloride labeled only in the amino group62). In the case of uracil,85 the two 15N-bonded protons gave two doublets centered at 10.78 and 10.96 ppm (measured downfield from internal tetramethyl-... 

The aminolysis of esters of pyrimidine occurs normally to yield amides. The reagent is commonly alcoholic ammonia or alcoholic amine, usually at room temperature for 20-24 hours, but occasionally under reflux aqueous amine or even undiluted amine are used sometimes. The process is exemplified in the conversion of methyl pyrimidine-5-carboxylate (193 R = Me) or its 4-isomer by methanolic ammonia at 25 °C into the amide (196) or pyrimidine-4-carboxamide, respectively (60MI21300), and in the butylaminolysis of butyl Uracil-6-carboxylate (butyl orotate) by ethanolic butylamine to give N-butyluracil-5-carboxamide (187) (60JOC1950). Hydrazides are made similarly from esters with ethanolic hydrazine hydrate. 

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