Imidazole carboxylate

Ester formation from polysaccharides can be achieved in several ways First by acylation of the OH groups with carboxylic or sulfonic acid azolides, second by converting the OH groups with imidazole carboxylates into carbonates, and third by reaction of an acid leash on the polysaccharide with an alcohol by means of CDI or analogous azolides. The acid leash might, for example, be a succinate attached to the polysaccharide. 

Carbonates of jS-cyclodextrin are prepared with imidazole carboxylates ... 

In a one-to-one ratio the reaction of CDI with (CH3)3Si(CH2)20H gave the corresponding imidazole carboxylate (97% yield), which was used in a selective protection of verrucarol, the parent compound of mycotoxines, as follows 12403... 

The benzyloxycarbonyl protecting group for amines is introduced in high yield using benzyl imidazole-carboxylate with a catalytic amount (5%) of dimethylamino-pyridine.[1953... 

Imidazole carboxylates of polyethylene glycols prepared with CDI react with amines to give polyethylene glycols (PEG) with carbamate end groups.12071 For example, PEG-... 

The following reaction of imidazole carboxylate of PEG was chosen for the purpose of introducing amino functions onto methoxypoly(ethylene glycol) chains (CH30-PEG) [184]... 

Amino-5-imidazole carboxylic acid (38) has been synthesized from 4-nitro-5-imidazole carboxylic acid by catalytic hydrogenation and shown [56JBC(218)175] to spontaneously decarboxylate at low pH to give 4-aminoimidazole (39). 

Five approaches to the synthesis of 5-amino-4-unsubstituted imidazoles (96) have been described and are summarized in Scheme 9. These are (a) reduction of 5-nitroimidazoles (97), (b) hydrolysis of carbamates and amides (98), (c) decarboxylation of imidazole carboxylic acids (99), (,d) ring transformations of 5-aminothiazoles (100), and (e) cyclisation of nitrile derivatives (101). 

Flash vacuum pyrolysis of methyl imidazol-2-yl carboxylate 290 at 750°C gave 20% yield of 268 via the corresponding ketene 291. Similar pyrolysis of methyl imidazol-l-yl carboxylate 292 gave 20% of a 1 1 2 mixture of compounds 267,268, and 296. This fact can be rationalized by the pathway depicted in Scheme 71. Ketenes 291 and 295 may be intermediates formed from 293 and 294, respectively. They are products of rearrangement of 292. Similar pyrolysis of 4-imidazole carboxylic acid anilide performed at 800°C gave 267 in 20% yield (86JOC306). 

From 133-tiiazines 23 and 5-amino-4-imidazole-carboxylic acids 24 a variety of purines and purine nucleosides 25 have been prepared via an inverse electron demand Diels-Alder reaction <99JA5833>. 

In this paper we report for the first time our studies of hydrogen bonding in the imidazole-carboxylate system, a common motif in enzyme active sites. The H solid state NMR data of polymorphic crystalline histidines were taken on a Chemagnetic... 

The structures of three cocrystals of caffeine having a 1 1 stoichiometry with various hydroxy-2-naphthoic acids have been reported [62], The anticipated imidazole-carboxylic acid supramolecular synthon was observed in caffeine cocrystals containing l-hydroxy-2-naphthoic acid and 3-hydroxy-2-naphthoic acid, while a hydrogen-bonded carboxylic acid dimer (and no hydroxyl-caffeine heterosynthon) was observed in the caffeine cocrystal with 6-hydroxy-2-naphthoic acid. 

Protein side groups, such as thiolate, imidazole, carboxylates some examples are given in Figure 1 in many cases dehydronation (i.e., loss of a hydron, H+) takes place upon binding to a metal. 

To date, the composition of active sites is known for many enzymes, the most probable action mechanisms are suggested, and comparison data exist on catalytic group properties in enzymes and free molecules in solutions. Note also that the chemical composition of catalytic active sites of enzymes is independent of the presence of any specific compounds. Moreover, the majority of them are the well-known compounds for homogeneous catalysis histidine imidazole, carboxylic groups of aspartic and aminoglutaric acids, flavins, hemins, etc. However, as homogeneous catalysts, they possess rather moderate or even poor catalytic activity in appropriate reactions. 

IM-COOH-OH cooperation. Polymers such as poly(4(5)-vinylimidazole-co-7-vinyl-7-butyrolactone), poly(IM-la), and poly(4(5)-vinylimidazole-co-acrylic acid-covinyl alcohol) derived from poly(4(5)-vinylimidazole-co-methyl acrylate-co-vinyl acetate), both of which contain imidazole, carboxylic acid and hydroxyl moieties are synthesized and studied as a model of a-chymotrypsin (29). The former has a relatively ordered sequence and the latter has a random one. Results are tabulated in Table 11. The polymers cited in the Tabel contain a similarly low quantity of imidazole moiety, so that the cooperation of two subsequent imidazole moieties need not be discussed. Polymers such as L-84, L-68, M-83 and A-84 have higher catalytic activities than the polymer V-82. This suggests that the catalytic activity of the imidazole moiety in the polymers is much promoted by the carboxylate moiety in the polymers. The catalytic activities of L-84 and L-68 which have an ordered sequence are more than twice as high as that of M-83, having a random sequence. From these results it is concluded that the introduction of the hydroxyl moiety which has little cooperative effect on the imidazole moiety in V-82 in this reaction conrfition into imidazole and carboxylate — containing polymer, increases... 

Table 11. Comparison of the catalytic activities of polymers containing imidazole, carboxylate, hydroxyl moieties or two of them...

Scheme 11 Direct synthesis of [99mTc(OH2)(L2)(CO)3] from [99mTc04] in water in the presence of [H3BC02H], 30 min, 95 °C, where L2 represents bidenate anionic ligands such as imidazole-carboxylic acid, picolinic acid or 2,4(5)-dipicolinic acid...

The fact that the four metal ligands provided by the transferrin apoprotein involve three different amino acid residues, i.e., histidine, tyrosine, and aspartate, is most interesting. Inorganic mononuclear complexes with such a variety of ligand types are not often encountered however, a Mn(III) complex with imidazole, carboxylate-, and phenoxide-type ligation has been structurally characterized. The complex [Mn(sal)2(ImH)2] (Fig. 7) (sal = salicylate) possesses two trans imidazoles and two salicylates disposed trans to one another (142). 

Imidazole carboxylic acids are readily converted into hydrazides,436 acid halides,437 amides,437-439 and esters,439-440 and they may be reduced to alcohols with lithium aluminum hydride,441 and to aldehydes by controlled potential reduction.442 Anodic oxidation of l-methylimidazole-5-acetic acid (94) using cooled platinum electrodes yields l,2-bis(l-methylimidazol-5-yl)ethane (95).443... 

Very recently, Nakajima and Okawa 164) investigated the hydrolysis of PNPA by Cyclo-(His-Glu-Cys-D-Phe-Gly)2. The second-order rate constant for the hydrolysis at pH 7.73 and 25 C was 19.61 M min for the cyclic decapeptide diacetate, which wt(s larger than 6.05 min for the corresponding linear pentapeptide triacetate and 1.33 M min for histidine hydrochloride, but smaller than 32.20 M min for cystein hydrochloride. The pH-rate profile for the reaction catalyzed by the cyclic decapeptide was bell-shaped with the maximum around pH 7.6, which indicates that the cyclic decapeptide is an acid—bs catalyst. On the other hand, the reaction by the cyclic decapeptide obeyed the Michaelis-Menten kinetics (i57), wdiich was found to involve a weak binding of the substrate = 2.7xlO M) prior to the unimolecular step. It is possible for imidazole, carboxyl, and thiol functions to cooperate in the cat ysis by the cyclic decapeptide, but the determination of the solution conformation would not be an easy task because of the thirty mem-bered ring. 

Deleuze-Masquefa et al. [15] showed that the microwave assisted bimolecular condensation of 2-imidazole carboxylic acid, followed by coupling with ortho-fluoroaniline and subsequent substitution on imidazole ring by Suzuki cross-coupling reaction gave the imidazo[l,2-a]quinoxaline (xiii) analogues in good yields. All the synthesized compounds showed high activities when evaluated for antitumor activities. 

The imidazole carboxylate group is phosphoiylated again and the phosphate group is displaced by the amino group of aspartate. Thus, a six-step process links glycine, formate, ammonia, hicarhonate, and aspartate to form an intermediate that contains all but two of the atoms necessary for the formation of the purine ring. 

Imidazole carboxylic esters of secondary or tertiary alcohols, such as 1053 and 1054,, form carbonates exclusively with primary alcohols (Scheme 253). Thus, 1054 is a useful reagent for the BOC-protection of primary hydroxyl groups < 19990L933>. In some cases, 1054 offers better selectivity than pivaloyl chloride in the protection of carbohydrates <1998S1787>. Similarly, l-(methyldithiocarbonyl)imidazole 1055 and its methyl triflate salt convert alcohols to ri -methyldithiocarbonates <1997SL1279> and amines to 6 -methyldithiocarbamates or thioureas <2000T629>. 

This is not surprising, since amide-forming reactions between amines and (activated) carboxylic acids proceed readily, and many optically active carboxylic acids are readily available. Furthermore, the diastereomeric amides produced are often well-resolved by LC or GLC. A variety of leaving groups (X in Eq, 1) have been used in the acylation reactitm, for example, chloride, imidazole, carboxylate, etc. 

Peptide-based polymers 62, containing imidazole, carboxyl, and hydroxymethyl functionalities, have been prepared from optically active 50d and tested as mimics of enzymes, such as chymotrypsin, which have the same functionalities (Scheme 41) [70]. These polymers exhibit markedly higher activities than the corresponding low molecular weight compounds in the hydrolysis of nitrophenyl and dinitrophenyl esters. Increased activities were... 

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