Acid Imidazolides Research Articles

Acylation of Meldrum’s acid with arylacetic acid imidazolides as a convenient method for the synthesis of 4-aryl-3-oxobutanoates

C-Acylation of Meldrum’s acid by (het)arylacetic acids in ethanol in the presence of 1,1′-carbonyldiimidazole leads to ethyl 4-(het)aryl-3-oxobutanoates in high yields.

ChemInform Abstract: Synthesis of 3‐(Pyrimidinyl)pyrrole Derivatives.

AbstractThe reaction of chloroacetic acid anilides (I) with pyrimidinylnitriles (II) leads to dihydropyrrol‐2‐ones (III), whilst the Claisen‐type acylation of nitriles (II) with N‐Boc‐α‐amino acid imidazolides followed by Boc‐deprotection and simultaneous cyclization gives rise to the isomeric dihydropyrrol‐3‐ones (V).

ChemInform Abstract: Acylation of Diethyl Phosphonoacetic Acid via the MgCl2/Et3N System: A Practical Synthesis of β-Keto Phosphonates.

Abstract A one pot simple procedure for the synthesis of β-keto phosphonates has been developed using the MgCl2/Et3N base system to generate the magnesium enolate of diethyl phosphonoacetic acid. This intermediate reacts with acid chlorides or imidazolides to give, after workup, the title compounds in good yields.

Synthesis of water-soluble cellulose esters applying carboxylic acid imidazolides

Water-soluble, non-ionic cellulose esters with a degree of substitution in the range from 0.11 to 3.0 were synthesized homogeneously using ionic liquids (1-butyl-3-methylimidazolium chloride, 1-ethyl-3-methylimidazolium chloride, and 1-allyl-3-methylimidazolium chloride) as reaction medium. Highly substituted 3,6,9-trioxadecanoic acid esters and 3,6-dioxaheptanoic acid esters of cellulose were obtained via the activation of the carboxylic acids with N,N’-carbonyldiimidazole. The products were characterized by the means of FTIR-, 1H- and 13C NMR spectroscopy.

Ice And The Origin Of Life

Sea ice occurs abundantly at the polar caps of the Earth and, probably, of many other planets. Its static and dynamic properties that may be important for prebiotic and early biotic reactions are described. It concentrates substrates and has many features that are important for catalytical actions. We propose that it provided optimal conditions for the early replication of nucleic acids and the RNA world. We repeated a famous prebiotic experiment, the poly-uridylic acid-instructed synthesis of polyadenylic acid from adenylic acid imidazolides in artificial sea ice, simulating the dynamic variability of real sea ice by cyclic temperature variation. Poly(A) was obtained in high yield and reached nucleotide chain lengths up to 400 containing predominantly 3'--> 5' linkages.

Catalytic Asymmetric Epoxidation of α,β‐Unsaturated Carboxylic Acid Imidazolides and Amides by Lanthanoid—BINOL Complexes.

AbstractFor Abstract see ChemInform Abstract in Full Text.

Catalytic asymmetric epoxidation of α,β-unsaturated carboxylic acid imidazolides and amides by lanthanide–BINOL complexes

Highly enantioselective catalytic asymmetric epoxidation of α,β-unsaturated carboxylic acid imidazolides and simple amides was developed. In the presence of 5–10mol% of lanthanide–BINOL complexes, the reaction proceeded smoothly with high substrate generality. In particular, in the cases of α,β-unsaturated amides, there was nearly perfect enantioselectivity (>99% ee). The corresponding epoxides were successfully transformed into many types of useful chiral compounds such as α,β-epoxy esters, α,β-epoxy amides, α,β-epoxy aldehydes, α,β-epoxy β-keto ester, and α- and β-hydroxy carbonyl compounds. B3LYP density functional studies were performed to predict substrate reactivity.

Unique reactivity of alpha,beta-unsaturated carboxylic acid imidazolides: catalytic asymmetric synthesis of alpha,beta-epoxy esters and alpha,beta-epoxy carboxylic acid derivatives.

Catalytic asymmetric synthesis of alpha,beta-epoxy esters and alpha,beta-epoxy carboxylic acid derivatives is described. Catalytic asymmetric epoxidation of alpha,beta-unsaturated carboxylic acid imidazolides using La-BINOL-Ph(3)As=O complex gave the corresponding alpha,beta-epoxy peroxy tert-butyl esters, which were directly converted to the alpha,beta-epoxy methyl esters by adding methanol to the reaction. This catalytic system had broad generality for epoxidation of various substrates. With the use of 5-10 mol% of the catalyst, both beta-aryl and beta-alkyl-substituted-alpha,beta-epoxy methyl esters were obtained in up to 91% yield and in up to 93% enantiomeric excess. In addition, efficient transformations of alpha,beta-epoxy peroxy tert-butyl esters into the alpha,beta-epoxy amides, alpha,beta-epoxy aldehydes, and gamma,delta-epoxy beta-keto esters are also reported.

Synthesis of Hydrophobic Starch Esters by Reaction of Starch with Various Carboxylic Acid Imidazolides

A novel efficient method of preparing hydrophobic starch esters with a DS = 1.55-2.0 using amylose enriched starch (amylomaize starch) or potato starch and a fatty acid imidazolide in DMSO as solvent is described. The fatty acid imidazolides can be easily prepared by conversion of the corresponding acyl chloride with imidazole in toluene according to a synthesis route developed by Staab et al. [1-4]. The by-product imidazole hydrochloride could be converted to imidazole by alkaline work up with Na 2 CO 3 . As compared with the direct esterification of starch in presence of a fatty acid chloride the presented synthesis method does not need toxic amines like pyridine as catalyst. Only a catalytic amount of a methanolic KOCH 3 solution is required. Furthermore no hydrolytic degradation of starch could be observed in contrast to the direct esterification reaction with a fatty acid chloride.

The selective reaction of primary amines with carbonyl imidazole containing compounds: selective amide and carbamate synthesis

A new highly selective synthesis of amides and carbamates is described. In both cases the syntheses involve the formation of carbonyl imidazole intermediates which subsequently undergo previously unreported selective reactions with primary amines. Acid imidazolides with sufficient chain length will exclusively react with primary amines even in the presence of secondary and tertiary functionality. The imidazole carboxylic esters of secondary or tertiary alcohols also react selectively with primary amines, forming controlled carbamate structures.

Synthesis and antitumor activity of some indeno[1,2-b]quinoline-based bis carboxamides

A series of bis(11-oxo-11H-indeno[1,2-b]quinoline-6-carboxamides) linked through the 6-carboxamides were prepared by coupling the requisite acid imidazolides with various diamines. Compounds with mono-cationic linker chains were more potent cytotoxins than the corresponding monomer in a panel of rodent and human cell lines, while those with the dicationic linker chains (CH2)2NR(CH2)2NR(CH2)2 and (CH2)2NR(CH2)3NR(CH2)2 showed extraordinarily high potencies (for example, IC50s of 0.18–1.4nM against human Jurkat leukemia; up to 1000-fold more potent than the parent monomer). As seen previously in the monomeric series, small, lipophilic 4-substituents significantly increased potency in cell culture. The dimeric compounds were all slightly to significantly more potent in the mutant JLA and JLD cell lines that under-express topo II, suggesting that this enzyme is not their primary target. An 11-imino-linked dimer was much less active, and an asymmetric indeno[1,2-b]quinoline-6-carboxamide/naphthalimide dimer was less active than the comparable symmetric bis(indeno[1,2-b]quinoline-6-carboxamide). Selected analogues were active against sub-cutaneously implanted colon 38 tumors in mice, giving growth delays comparable to that of the clinical topo I inhibitor irinotecan at up to 10-fold lower doses. These compounds form an interesting new class of putative topo I inhibitors.

Acylation of Diethyl Phosphonoacetic Acid Via the MgCl2/Et3N System: A Practical Synthesis of β-Keto Phosphonates

A one pot simple procedure for the synthesis of β-keto phosphonates has been developed using the MgCl2/Et3N base system to generate the magnesium enolate of diethyl phosphonoacetic acid. This intermediate reacts with acid chlorides or imidazolides to give, after workup, the title compounds in good yields.

Syntheses of substituted 2‐(l‐methyl‐2‐imidazolyl)quinolines

AbstractReaction of methyllithium with 1‐methy1‐2‐imidazolecarboxaldehyde afforded the corresponding alcohol 2. Oxidation of compound 2 with manganese dioxide gave 2‐acety1‐1‐methylimidazole (3). Using compound 3 and substituted isatins 4, the corresponding quinoline‐4‐carboxylic acids (5) were prepared. The reaction of acid imidazolides of 5 with appropriate amines yielded the amides 6. Carbamic acid esters 10 were prepared by the Curtius rearrangement in good yield. Substituted quinolin‐4‐amines 13 were obtained by the acid hydrolysis of compound 10 (R1 = t‐Bu). Alkylation of amines 13 with diakylaminoalkyl chlorides gave compounds 14.

Conformational changes associated with activation of bee venom phospholipase A2.

Bee venom PLA2 possesses a binding site for long-chain fatty acids that can be acylated by long-chain fatty acid imidazolides [Drainas, D. and Lawrence, A.J. (1978) Eur. J. Biochem. 91, 131-138]. Occupation of the site either by oleic acid or the oleoyl residue enhances the catalytic activity by 45.7-fold in the presence of 20% 1-propanol and occupation of the site by the oleoyl residue increases the lytic activity against rabbit erythrocytes by 60-fold. Treatment of the enzyme with oleic acid and glutaraldehyde is known to produce irreversible activation [Lawrence, A.J. and Moores, G.R. (1975) FEBS Lett. 49, 287-291]. Here we show that reduction of the glutaraldehyde-treated enzyme with borohydride stabilizes the activated state and enables the fatty acid to be removed, revealing that a large proportion of the induced activation does not require the presence of oleic acid and indicating that activation is due to a change in the conformation rather than the hydrophobicity of the protein. A kinetic study of enzyme activated by oleoyl imidazolide showed that this modification stabilizes the protein against reversible inactivation by 1-propanol. Comparison of the CD spectra of native and oleoyl imidazolide-activated enzyme shows a change in secondary structure with apparent increase in both alpha-helix and beta-sheet content. During reaction of the enzyme with oleoyl imidazolide, the protein fluorescence shows a biphasic response with an initial fall attributed to occupation of the binding site followed by a progressive decrease with a shift of the emission maximum from 341 to 348 nm. The rate of the second phase closely matched the rate of increase in catalytic activity of the enzyme. Free oleic acid caused a rapid fall in fluorescence emission without the subsequent slow change. These results support the proposal that oleic acid or the oleoyl residue occupy a very similar site on the protein and that occupation of this site increases the exposure of one or both of the Trp residues to the aqueous environment. Binding studies show that activation by oleoyl imidazolide does not increase the affinity of the enzyme for the erythrocyte membrane. It is proposed that occupation of a long-chain fatty acid binding site on the enzyme enhances catalytic activity by changing the conformation of the protein rather than acting as a hydrophobic anchor to the substrate surface.

ChemInform Abstract: Facile Reduction of Carboxylic Acid Imidazolides to Primary Alcohols in the Presence of Water.

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Facile Reduction of Carboxylic Acid Imidazolides to Primary Alcohols in the Presence of Water

A convenient protocol for selective reduction of carboxylic acid imidazolides to primary alcohols, which tolerates bromo, nitro, cyano, ester and amide functional groups, is disclosed.

Mixed anhydrides (phosphoric-carboxyl) are also formed in the esterification of 5′-amp with n-acetylaminoacyl imidazolides: Implications regarding the origin of protein synthesis

Procedures for the formation of aminoacyl esters of monoribonucleotides with aminoacyl imidazolides were first reported by Gottikh et al. and summarized in 1970. This reaction has been widely used by us and numbers of other workers as a convenient means of preparing aminoacyl esters of nucleotides. We have previously reported that, under conditions of excess imidazolide, large amounts of bis 2', 3' esters are formed in addition to the monoesters, (Lacey et al., 1991). However, to our knowledge, no one has reported that in addition to the esters, relatively large amounts of the mixed anhydride, with the amino acid carboxyl attached to the phosphate, are also formed at short reaction times. We report here on the relative amounts of anhydride and esters formed in this reaction of racemic mixtures of eleven N-acetyl amino acid imidazolides with 5'-AMP and discuss the relevance of the findings to the origin of protein synthesis.

Dipeptide Analogues: Synthesis of C-Terminal p-Nitrobenzyl-3-ketoesters of N-Protected Amino Acids

Abstract Nitrogen protected amino acid imidazolides undergo facile carbon acylation with magnesium p-nitrobenzylmalonate dihydrate in THF to give pseudodipeptides in 30-79% isolated yield.

Stereospecificity of peptide synthesis by means of phosphorus derivatives: a model of peptide synthesis in molecular evolution

A hypothesis is presented to explain the prebiotic formation of optically pure oligo- and polypeptides from racemic amino acids. Stereospecific condensation reactions favouring the formation of isotactic stereosequences ( l-l and d-d blocks) are a basic requirement of this hypothesis. Since phosphorus derivatives such as polyphosphates or nucleic acid imidazolides were postulated to be prebiotic condensing reagents, a variety of peptide syntheses by means of phosphorus derivatives was investigated. Dipeptides and tripeptides were prepared from N-protected d,l-amino acids or d,l-amino acid esters, and d,l-leucine and d,l-valine were subjected to condensation polymerizations. The stereosequences were analysed by means of 13C n.m.r. spectroscopy. More than 80% of all condensations were more or less stereospecific and in all cases isotactic sequences were predominant. In the case of poly( d,l-leucines), 13C n.m.r. cross-polarization/magic angle spinning ( CP/MAS) spectra revealed the formation of α-helical blocks.

ChemInform Abstract: CONVENIENT SYNTHESIS OF α‐ACYLAMINO ALDEHYDES

AbstractDie Carbonsäuren (II) lassen sich nach Umsetzung mit Carbonyldiimidazol (I) als Imidazolide mit Diisobutylaluminiumhydrid zu Aldehyden (III) reduzieren.