4- Aminoimidazole formation

The pathways for thiamine biosynthesis have been elucidated only partiy. Thiamine pyrophosphate is made universally from the precursors 4-amino-5-hydroxymethyl-2-methylpytimidinepyrophosphate [841-01-0] (47) and 4-methyl-5-(2-hydroxyethyl)thiazolephosphate [3269-79-2] (48), but there appear to be different pathways ia the eadier steps. In bacteria, the early steps of the pyrimidine biosynthesis are same as those of purine nucleotide biosynthesis, 5-Aminoimidazole ribotide [41535-66-4] (AIR) (49) appears to be the sole and last common iatermediate ultimately the elements are suppHed by glycine, formate, and ribose. AIR is rearranged in a complex manner to the pyrimidine by an as-yet undetermined mechanism. In yeasts, the pathway to the pyrimidine is less well understood and maybe different (74—83) (Fig. 9). 

Theoretical studies of the relative stabilities of tautomers 14a and 14b were carried out mostly at the semiempirical level. AMI and PM3 calculations [98JST(T)249] of the relative stabilities carried out for a series of 4(5)-substituted imidazoles 14 (R = H, R = H, CH3, OH, F, NO2, Ph) are mostly in accord with the conclusion based on the Charton s equation. From the comparison of the electronic spectra of 4(5)-phenylimidazole 14 (R2 = Ph, R = R3 = H) and 2,4(5)-diphenylimidazole 14 (R = R = Ph, R = H) in ethanol with those calculated by using ir-electron PPP method for each of the tautomeric forms, it follows that calculations for type 14a tautomers match the experimentally observed spectra better (86ZC378). The AMI calculations [92JCS(P1)2779] of enthalpies of formation of 4(5)-aminoimidazole 14 (R = NH2, R = R = H) and 4(5)-nitroimidazole 14 (R = NO2, R = R = H) point to tautomers 14a and 14b respectively as being energetically preferred in the gas phase. Both predictions are in disagreement with expectations based on Charton s equation and the data related to basicity measurements (Table III). These inconsistencies may be... 

These findings accord with the semiempirical AMI calculations [92JCS(P1)2779] of the heats of formation of all theoretically possible tautomeric forms of 4-aminoimidazole 53. The most stable are the tautomers 53a AHf = 213 kJ mol ) and 53d AHf = 215 kJ mol ) (Scheme 29). All... 

One of the steps in the biosynthesis of a nucleotide called inosine monophosphate is the formation of aminoimidazole ribonucleotide from formyjglycin-amidine ribonucleotide. Propose a mechanism. 

A microwave-assisted, one-pot, two-step protocol was developed for the construction of polysubstituted 2-aminoimidazoles 101 via the sequential formation of imidazo[l,2-a]pyrimidinium salts from readily available 2-aminopyrimidines 99 and a-bromocarbonyl compounds 100, followed by opening of the pyrimidine ring with hydrazine <06OL5781>. A... 

An unexpected reaction occurs when 2-alkyl-4(5)-nitroimidazoles (27 R = alkyl) are reduced in protic solvents [92JCS(P1)2779]. Catalytic hydrogenation of 2-methyl-4(5)-nitroimidazole (27 R = Me) in a solution of acetic anhydride and acetic acid gave 4,4 -diacetamido-2,2 -dimethyl-5,5 -diimidazole (32 yield 10%) in addition to the expected 4-acetamido-l-acetyl-2-methylimidazole (28%). Similarly, reduction of the 2-alkyl-4(5)-nitroimidazoles (27 R = Me, Et, iPr) in ethanol solution in the presence of diethyl ethoxymethylenemalonate [EMME (135)] gives predominantly the 5,5 -diimidazole adducts (33). The formation of these products (33) is believed to involve an electrophilic addition of the starting material (27) to the electron-rich aminoimidazoles (25) [92JCS(P1)2779]. Interestingly, replacement of ethanol by dioxane suppressed diimidazole formation. 

Hunter and Nelson (41 Mil) attempted the preparation of 4(5)-aminoimidazole (25 R = H) from its acetyl derivative (28 R = H, R1 = Me), which they obtained by reduction of 4(5)-nitroimidazole (27 R = H) with tin(II) chloride in acetic anhydride. The authors noted that hydrolysis of compound (28 R = H, R = Me) with aqueous acids resulted in fission of the imidazole ring and formation of acetic acid, formic acid, ammonia, and glycine. Base hydrolysis gave similar results (41 Mil), although a trace of 4(5)-aminoimidazole (25 R = H) was detected. 

An unusual observation was noted when ethanolic solutions of 2-alkyl-4(5)-aminoimidazoles (25 R = alkyl) were allowed to react with diethyl ethoxymethylenemalonate (62 R = H) [92JCS(P1)2789]. In addition to anticipated products (70), which were obtained in low yield ( 10%), the diimidazole derivatives (33 R = alkyl) were formed in ca.30% yield. The mechanism of formation of the diimidazole products (33) has been interpreted in terms of a reaction between the aminoimidazole (25) and its nitroimidazole precursor (27) during the reduction process. In particular, a soft-soft interaction between the highest occupied molecular orbital (HOMO) of the aminoimidazole (25) and the lowest unoccupied molecular orbital (LUMO) of the nitroimidazole (27) is favorable and probably leads to an intermediate, which on tautomerism, elimination of water, and further reduction, gives the observed products (33). The reactions of amino-imidazoles with hard and soft electrophiles is further discussed in Section VI,C. 

A key requirement for diimidazole formation appears to be substitution of the 2-position, since 4(5)-aminoimidazole (25 R = H) gave only the monomeric species (70 R = H). The choice of solvent is also important when dioxane replaced ethanol as solvent, diimidazole formation was suppressed [92JCS(P 1)2789]. 

During studies of the formation of 5-aminothiazoles (113), Heilbron, Cook, and Downer (48JCS1262) noted that under certain conditions 5-aminothiazoles (113) were converted into isomeric 5-aminoimidazoles. 

The effect of 6-mercaptopurine on the incorporation of a number of C-labelled compounds into soluble purine nucleotides and into RNA and DNA has been studied in leukemia L1210, Ehrlich ascites carcinoma, and solid sarcoma 180. At a level of 6-mercaptopurine that markedly inhibited the incorporation of formate and glycine, the utilization of adenine or 2-aminoadenine was not affected. There was no inhibition of the incorporation of 5(or 4)-aminoimidazole-4(5)-carboxamide (AIC) into adenine derivatives and no marked or consistent inhibition of its incorporation into guanine derivatives. The conversion of AIC to purines in ascites cells was not inhibited at levels of 6-mercaptopurine 8-20 times those that produced 50 per cent or greater inhibition of de novo synthesis [292]. Furthermore, AIC reverses the inhibition of growth of S180 cells (AH/5) in culture by 6-mercaptopurine [293]. These results suggest that in all these systems, in vitro and in vivo, the principal site at which 6-mercaptopurine inhibits nucleic acid biosynthesis is prior to the formation of AIC, and that the interconversion of purine ribonucleotides (see below) is not the primary site of action [292]. Presumably, this early step is the conversion of PRPP to 5-phosphoribosylamine inhibited allosterically by 6-mercaptopurine ribonucleotide (feedback inhibition is not observed in cells that cannot convert 6-mercaptopurine to its ribonucleotide [244]. 

By carrying out the Ugi-reaction with a large number of isonitrils, aldehydes, carboxylic acids, and amines, it was found that formation of different products of the reaction occurred depending on the structure of the amines used. Thus, 3-aminoimidazoles 88 were isolated when aldehyde reacted with isocyanide and heterocyclic aromatic 2-aminoazine as primary amine (Scheme 38). 

Dacarbazine Dacarbazine, 5-(3,3-dimethyl-l-(riazeno)imidazol-4-carboxamide (30.6.5), is made by diazotation of 5-aminoimidazol-4-carboxamide with nitrous acid, which results in the formation of 5-diazoimidazol-4-carboxamide (30.6.4). Reacting this with dimethy-lamine gives the desired dacarbazine (30.6.5) [146]. 

Pramanik s group. He reasoned that the hydrolysis of dihydrohypoxanthine to 5-aminoimidazole-4-carboxamide (AIC) (see Scheme 19 and Figure 14 in Case Study 2) might be conveniently carried out using microwave irradiation. He dissolved dihydrohypoxanthine trifluoroacetate salt (81.1 mg) in 1 1 trifluoroacetic acid water (2 ml) and micronized the solution for 2 min at ambient pressure. After this time the electrospray-MS spectrum of the solution indicated that substantial AIC formation had occurred (Figure 1). 

Synthesis of imidazoles, oxazoles, and thiazoles by CC bond formation or 1,3-dipolar addition 4-Aminoimidazoles 266 are formed on base treatment of the appropriate precursors 265 (Scheme 130) <1975HCA2192>. Similarly the 4-aminothiazole 268 is obtained from the cyanoamidine 267 (Scheme 131) <1973JPR497>. 

This report covers two topics (1) The generation of 2-thioxo-2,4-dihydro-3fT-imidazol-l-ium-l-imides as intermediates in the course of [3+2] cycloaddition reactions of azoalkenes and thiocyanic acid resulting in the formation of l-aminoimidazole-2-thione derivatives some further reactions of these heterocycles are presented as well. (2) The rhodium-catalyzed intramolecular interaction of co-diazenyl a -diazo ketones giving rise to the formation of mostly two cyclic azomethine imine isomers with an exocyclic terminal nitrogen atom and with all three... 

An interesting corollary of these reactions is the formation of 2-aminoimidazoles from guanidines and suitably substituted ketones. At -10 °C in methanol, l-phenylpropane-1,2-dione reacts with 1,1-disubstituted guanidines to give 2-(disubstituted amino)-4-hydroxy-4-methyl-4H-imidazoles (121) which, on catalytic hydrogenation, give excellent yields of... 

Cyclization of thioureidoimidazoles in the presence of sulfur-extracting agents such as mercury salts may favour 2-aminopurine formation. Thus 5-aminoimidazole-4-(iV-methyl)carboxamide (354) and some 2-substituted derivatives with phenyl isothiocyanate afforded the phenylthioureidoimidazole which when heated with mercury(II) salts produced 1,N-dimethylisoguanine and 8-substituted derivatives (355), respectively (Scheme 146) (50JCS1888). 

Useful precursors for the preparation of substituted hypoxanthine derivatives are alkyl 4(5)-aminoimidazole-5(4)-carboxylates. Thus, reaction of ethyl 4-amino-l-arylimida7ole-5-carb-oxylates with thioamides in the presence of a catalytic amount of formic acid gives 2-substituted 7-arylhypoxanthines, e.g. formation of l. °... 

The pharmacologically important 6-sulfanylpurine (8) is synthesized by condensation of 5-aminoimidazole-4-carbothioamide with ethyl formate. 

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