Uracil ring amines

Researchers at FMC Corporation have synthesized 3-(4,6-substituted benzoheterocy-clyl)uracil herbicides. The uracil ring synthesis is based on conversion of aryl amines into isocyanates68. A useful fluorinated aniline herbicide is fluometuron. Chlorination of 2-methylpyridine (102), followed by animation at the 4-position, and hydrolysis, yields the hormone-weedkiller Picloram (103) (Scheme 22). 

The amination of position 6 of the uracil ring to form cytosine appears to take place by different pathways in bacteria and in mammalian tissue. An enzyme in Escheridiia adi catalyzes the amination of the nucleotide triphosphate according to Eq. (2) (4, 5). Uracil, uridine, and uridylic acid are not aminated in this system (4). 

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. 

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. 

The production of CTP by amination of UTP. The conversion of the pyrimidine ring of uracil to cytosine occurs at the level of the nucleotide triphosphate. The enzyme responsible for this conversion is known as cytidine triphosphate synthase. 

Silylation-amination fails with 5-ring-hydroxy-N-heterocycles such as 2-benzoxazolone since, at temperatures of I30°C, the 2-trimethylsilyloxy-benzoxazole (190) is in equilibrium with its open form 191 (73LA772), which reacts readily with benzylamine to eventually form N,N -dibenzylurea (CftHjCHj—NH-CO—NH—CH2C6H5). The silylation-amination procedure has been applied to the amination of 6-oxadihydro-uracil (193) with benzylamine to 194 (77JMCI34). The 5-deazapteridine derivative 195 affords, with ammonia/HMDS in the presence of p-toluenesulfonic acid, the diaminated product 1% in 74% yield (86JMC709). 

Only five common nitrogen heterocycles are used to form these nucleosides. Three compounds have one ring, and are derived from a nitrogen heterocycle called pyrimidine. Two are bicyclic, and are derived from a nitrogen heterocycle called purine. These five amines are referred to as bases. Each base is designated by a one-letter abbreviation, as shown in the names and structures drawn. Note that uracil (U) occurs only in ribonucleosides and thymine (T) occurs only in deoxyribonucleosides. 

Irradiation of l,3,7-trimethyl-8-azaxanthine (343) in a solution of diethyl-amine in methyl cyanide yields the uracil derivative (344) (Scheme 132). ° A hypoxanthine analogue (345) has been prepared by ring-closure of the corresponding imidazo-aminosulphonamide with triethyl orthoformate. 

Amino-l,3-dimethyl-5-nitrosouracil (270), reported last year as a highly versatile precursor for the purine and pteridine ring systems, has again found use (Scheme 63) in a new synthesis of 6-hydroxy-pteridines (271). Photo-decomposition of 6-azido-l,3-dimethyluracil as a solution in a secondary or primary amine has been used as a convenient method of preparing 6-alkylamino-5-amino-uracils. The procedure has now been extended ... 

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