Imidazolone derivatives

Shaw and McDowellhave prepared imidazolone derivatives by cyclization of a-acylamino amides. In a variation of this reaction the azlactone (30) was gradually converted to the hydroxamic acid (31) by methanolic hydroxylamine. Sodium methoxide and hydroxylamine readily gave the acyclic hydroxamic acid (32) which could be cyclized to 31 by dilute acid. Benzyloxyurea has been used in the sjrnthesis of pyrimidine hydroxamic acids (33) by reaction with /S-diketones followed by catalytic hydrogenation of the benzyl group. Protection... 

A series of benzimidazole and benzimidazolone derivatives from the Janssen laboratories has provided an unusually large number of biologically active compounds, particularly in the area of the central nervous system. Reaction of imidazolone itself with isopropenyl acetate leads to the singly protected imidazolone derivative 51. Alkylation of this with 3-chloro-l-bromopropane affords the functionalized derivative Use of this... 

Structure of GFP and its chromophore. To study the chro-mophore of GFP, a sample of GFP was denatured by heating it at 90°C. It was digested with papain, and then a peptide containing the fluorophore was isolated and purified from the digested mixture. The structural study of the peptide has indicated that the chromophore of GFP is an imidazolone derivative shown below (Shimomura, 1979). This chromophore structure was confirmed later by Cody etal. (1993) in a hexapeptide isolated from GFP. It is intriguing that the structure of the GFP chromophore is a part of the structure of coelenterazine. 

Cycloaddition of homochiral imidazolone-derived nitrone (490) to various alkenes (D1,D2) (Scheme 2.239) (Table 2.18) affords good yields of cycloadducts (491 a-c) with high stereoselectivity (738). 

The most important synthetic routes have been from ketones by cycliza-tion, by the transformation of imidazolone derivatives, and by the reaction between 1//-imidazoles and electrophiles. 

One interesting difference between the known examples of 2H- and 4H-imidazoles is that nearly all in the latter group contain at least one hetero-linked substituent. This arises because the major synthetic approach is via imidazolone derivatives (see next section) a second important route using 1,2-diketones places an OH group at C-4, and electrophilic additions to 1//-imidazoles also tend to introduce heteroatoms at this site. 

Electrophilic attack of the HN—C=X moiety in imidazolone derivatives at X (which has usually been sulfur) can result in 4//-imidazoles. This has been the most commonly used method for the preparation of these compounds. 

Moreover, the oxidation of methional to ethylene has been proposed (Beauchamp and Fridovich 1970 Biaglow et al. 1997), and the formation of allantoin (Grootveld and Halliwell 1987 Halliwell et al. 1988) from uric acid as well as the imidazolone derivative from histamine (Ching et al. 1995) have been suggested as an index of OH action in vivo (Halliwell et al. 1988). 

Another possible aspect of histidine peptide cleavage is introduced by the great lability of 4(5H)-imidazolones (CXXXIII) (Freter el al., 19.57 Brown and Kies, 1959). In their lability and eagerness to open up to forma-raidino acids (CXXXIV) they almost resemble anhydrides (Kny and Witkop, 1959). It is not unlikely that such 4(5H)-imidazolones can be produced nonenzymatically. Such selective oxidation of a histidine peptide to a 4(5H)-imidazolone derivative introduces the possibility of translacta-... 

Heterocyclic ketene aminals (78) react smoothly with ethyl bromoacetate, and pyrroloimidazoles (79) are obtained by further cyclocondensation of alkylation products <89CB95>. Another procedure is based on reaction of 1,2-ethylenediamine and ethyl levulinate (80) under microwave irradiation giving (81) <92SL219>. Compound (80) also reacts with glycinamides, and alaninamides <93JMC4214> to give the corresponding pyrrolo[l,2-a]imidazolone derivatives (82). These reactions are shown in Scheme 13. 

Within double-stranded oligonucleotides, the imidazolone derivative was not the major product. The HPLC peak detected at 260 nm (Fig. 29A) and containing this lesion (in-line ESI-MS data) eluted at a retention time of 40.1 min. This product incorporated one oxygen atom from labeled water and the mechanism of its formation could be attributed to a nucleophilic attack of a water molecule at the former C5 of guanine 253). 

A similar approach is adopted for the synthesis of imidazolone derivatives of 1,3,5-oxadiazines 299 in 58-67% yield <2000EJC389>. 

Dantoin (l,3-di(hydroxymethyl)-5,5-dimethylimidazole-2,4-dione, 24) is an imidazolone derivative. The compound is water-soluble, stable and non-corrosive with a slight odour of formaldehyde. Its mode of action is attributed to its ability to release formaldehyde. Its rate of release is greater at higher pH values, although it is more stable in the range pH 6 8 [13],... 

Imidazolone (Glyoxalone) Derivatives. Amides of a-acylamino-acrylic acids can be converted into imidazolone derivatives as shown in the equations ... 

Certain imidazolone derivatives can be converted into dipeptides as follows. ... 

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