N-acylated Products Research Articles

Highly efficient chemoselective N-acylation with water microreaction system in the absence of catalyst

A high-speed, highly efficient chemoselective N-acylation by anhydride was achieved in the absence of catalyst for exothermic (DeltaH>0) and endothermic (DeltaH<0) acylation of various amines and anilines with the microreaction system of ambient water (micro-onH2O) and subcritical water (micro-subH2O), where the desired N-acylated products are chemoselectively obtained with high yield(s) and excellent selectivity (>95%).

Synthesis of (S)-1-(2-chloroacetyl)pyrrolidine-2-carbonitrile: A key intermediate for dipeptidyl peptidase IV inhibitors

An alternative and practical synthesis of (S)-1-(2-chloroacetyl)pyrrolidine-2-carbonitrile was achieved. Reaction of L-proline with chloroacetyl chloride was followed by conversion of the carboxylic acid moiety of the resulting N-acylated product into the carbonitrile via the corresponding amide intermediate. The synthesized pyrrolidine derivative was utilized to prepare DPP-IV inhibitor Vildagliptin.

Protein N-Acylation: H2O2-Mediated Covalent Modification of Protein by Lipid Peroxidation-Derived Saturated Aldehydes

Various lines of evidence indicate that the oxidative modification of protein and the subsequent accumulation of the degenerated proteins have been found in cells and tissues during aging, oxidative stress, and in a variety of pathological states. The critical agents that give rise to this protein degeneration may be represented by aldehydes. Although the covalent modification of proteins by aldehydes alone has been well-studied, the effect of reactive oxygen species, such as H2O2, upon aldehyde modification of the protein has received little attention. We have now established a unique protein modification in which H2O2 and, to a lesser extent, alkyl hydroperoxides mediate the binding of alkanals to the lysine residues of protein to generate structurally unusual N-acylation products. Upon the reaction of a lysine-containing peptide, N(alpha)-benzoylglycyl-lysine, with hexanal in the presence of H2O2, a product containing one molecule of hexanal per peptide was detected. On the basis of the chemical and spectroscopic evidence, the product was identified to be the acylation product, N(epsilon)-hexanoyllysine. H2O2 mediated the N-acylation of the lysine derivative by the saturated aldehydes of 1-6 carbons in length. The H2O2-mediated acylation of the protein was immunochemically confirmed by reaction of the proteins with hexanal in the presence of H2O2. Furthermore, the enhanced N-acylations (N-acetylation and N-hexanoylation) were also observed in the kidney of rats exposed to ferric nitrilotriacetate, a well-characterized inducer of oxidative stress. Mechanistic studies using a phosphonium lysine derivative suggest a Baeyer-Villiger-like reaction proceeding through peroxide addition to the aldehyde Schiff base. These data suggest that the hydroperoxides, including H2O2, might be involved not only in the oxidative modification of protein but also in the covalent binding of the saturated aldehydes to proteins under oxidative stress.

A new and efficient method for the facile synthesis of N-acyl sulfonamides under Lewis acid catalysis

The N-acylation of sulfonamides with carboxylic acid anhydrides in the presence of Lewis acids is described. Several Lewis acids such as BF 3·Et 2O, ZnCl 2, MoCl 5, TiCl 4, B(C 6F 5) 3, Sc(OTf) 3 and I 2 were found to catalyze the reaction efficiently to furnish the N-acylated products in good yields under solvent-free conditions. The reactions of various sulfonamides were studied with different carboxylic acid anhydrides including the less reactive benzoic and pivalic anhydrides, in the presence of 3 mol % ZnCl 2 as the catalyst. Carboxylic acids were also successfully used as acylating agents via the mixed anhydride method.

Acyl iodides in organic synthesis: VIII. Reactions with amino acids

Reactions of acyl iodides RCOI (R=Me, Ph) with glycine, β-alanine, and γ-aminobutyric acid were investigated. The reaction proceeded easily at room temperature without solvent involving both functional groups H2N and COOH. The prevalence of one of the reaction directions depends on the acidity of the amino acid. The more acidic glycine (pКa 2.4) reacts with RCOI affording mainly N-acylated product, whereas β-alanine (pКa 3.60) and especially γ-aminobutyric acid (pКa 4.06) are predominantly involved into exchange iodination furnishing the corresponding aminoacyl iodides.

Polymer Supported Carbodiimide Strategy for the Synthesis of N‐Acylated Derivatives of Deoxy‐ and Ribo‐Purinenucleosides Using Active Esters.

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Polymer supported carbodiimide strategy for the synthesis of N-acylated derivatives of deoxy- and ribo purinenucleosides using active esters

A cost-effective synthetic strategy has been used for the selective protection of the exocyclic amino function of purine nucleosides. Instead of using the common protecting groups in their chloride or anhydride forms, the less expensive and nontoxic acidic form was chosen. The acids were first activated to an active ester form using DCC and further successfully used for N-acylation of purine nucleosides. The contamination of the N-acylated product with DCU was inconvenient and was avoided by use of polymer supported-carbodiimide that has the additional advantage of reusability.

Chemistry and Structure of Diterpenoids: X. Isosteviol Amides

Acylation of amino alcohols with isosteviol chloride, depending on the reactant ratio, leads to formation of either bis-isosteviol derivatives or N-acylation products. Reactions of aromatic diamines with 2 equiv of isosteviol chloride give the corresponding N,N′-bis(isostevioyl) derivatives.

The Synthesis of Some Chiral 2‐Aminoalkyloxazole‐5‐carboxylates from Isoxazol‐5(2H)‐ones.

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The Synthesis of Some Chiral 2‐Aminoalkyloxazole‐4‐carboxylates from Isoxazol‐5(2H)‐ones.

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Substituted 1,2-Thiazetidine 1,1-Dioxides. Synthesis and Properties of N-Alkylated and N-Acylated Derivatives of 1,2-Thiazetidine-3-acetic Acid 1,1-Dioxide

1,2-Thiazetidine-3-acetic acid 1,1-dioxide was N-alkylated using bromoacetates, and N-acylated using either acyl chlorides, protected amino acid fluorides, or N-protected amino acid NCA, which seemed to be the most universal method. Most of the obtained “β-sultam peptides” were sensitive against humidity, they hydrolyzed forming sulfonic acids, and reactions with amines resulted in sulfonamides. Reactions of N-acylated products showed that the sulfonyl group was faster attacked than the imide structure.

Practical Synthesis of 8‐Acyl‐7‐alkyl‐1,6‐naphthyridin‐5(6H)‐ones.

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The Synthesis of Some Chiral 2-Aminoalkyloxazole-5-carboxylates from Isoxazol-5(2H)-ones

Ethyl 5-oxo-2,5-dihydroisoxazole-4-carboxylates have been N-acylated by a number of natural and synthetic phthalimidylamino acids in the presence of carbodiimides. The N-acylated products form the corresponding 2-aminoalkyloxazole-5-carboxylates smoothly when irradiated at 300 nm in acetone.

The Synthesis of Some Chiral 2-Aminoalkyloxazole-4-carboxylates from Isoxazol-5(2H)-ones

Ethyl 4-methyl-5-oxo-2,5-dihydroisoxazole-3-carboxylate can be N-acylated by a number of natural and synthetic phthalimidylamino acids in the presence of carbodiimides. The N-acylated products form the corresponding oxazoles smoothly when irradiated at 300 nm in acetone. Removal of the phthalimido protecting group then gives 2-aminoalkyloxazole-4-carboxylate esters in good overall yields, and without significant racemization at any step.

Practical synthesis of 8-acyl-7-alkyl-1,6-naphthyridin-5(6 H)-ones

Reaction of a set of enaminones with 2-chloronicotinoyl chloride or 2,6-dichloro-5-fluoronicotinoyl chloride mainly leads to N-acylation products which cyclize directly or reacting with sodium hydride to give 8-acyl-7-alkyl-1,6-naphthyridin-5(6 H)-ones. Due to their easy availability these compounds are attractive precursors for synthesis of polycondensed heterocycles like naphtho[2,3- h][1,6]naphthyridin-5-ones and pyrido[3,2- c][1,6]naphthyridin-6-ones.

Electrogenerated base-induced N-acylation of chiral oxazolidin-2-ones. Part 2.

An improved and efficient electrochemical N-acylation of chiral oxazolidin-2-ones has been achieved. The generation of the nitrogen anion is obtained under mild conditions and without addition of base or probase, by direct electrolysis of a solution of MeCN-TEAP containing the oxazolidinone. Acylation agents (acid chlorides or anhydrides) were added at the end of the electrolysis. N-Acylated products were isolated in high to excellent yields.

Syntheses and interfacial behaviour of neoglycolipid analogues of glycosyl ceramides

Four glycosyl ceramides analogues having d-galactose or 2-acetamido-2-deoxy- d-glucose moieties linked to enantiomeric lipids have been synthesised to study their interfacial behaviour at the air ∣ water interface. The lipid chains were prepared in two steps by opening 1,2-epoxyhexadecane using Jacobsen kinetic hydrolytic resolution (KHR) followed by an azidosilylation reaction of the diol so obtained. Glycosylation reactions were realised either with 2,3,4,6-tetra- O-benzoyl-α- d-galactopyranosyl trichloroacetimidate or 1,3,4,6-tetra- O-acetyl-2-allyloxycarbonylamino-2-deoxy-β- d-glucopyranose as donors and (2 R)- or (2 S)-2-azidohexadecanol derivatives as acceptors. Transformation of the azido glycosides into N-acylated products was done by a modified Staudinger reaction in the presence of fatty acyl chlorides. The four neoglycolipids are able to form a condensed monolayer at the air ∣ water interface; their π-A isotherm diagrams are similar to that described for the natural glycosyl ceramides. The detailed analysis of the isotherms, taking into account the chirality of the lipid chains, allowed to determine the contribution of the different parts of the molecule under the monolayer packing.

Structural Features of Primary 6-Aminopentafulvenes and Some of Their Derivatives

Starting from 6-amino-6-methylpentafulvene (2) “ortho”-C-acylation or N-acylation can be achieved selectively. Treatment of 2 with phthaloyl-protected amino acid chlorides derived from alanine (3a) or valine (3b) leads exclusively to the formation of the “ortho”-C-acylated derivatives 4, isolated as racemates. Optically active N-acylated products 7 were prepared by coupling 5, obtained by NH deprotonation of 2, with the 1-hydroxybenzotriazole (HOBt) active-esters of alanine (6a), valine (6b), or leucine (6c) bearing benzylprotected amino groups. Complexes 2, 4a, 4b, and 7a were characterized by X-ray diffraction. Electron-withdrawing groups attached at the “ortho” ring position lead to a shortening of the external C6−N bond, whereas electron-withdrawing groups bound to the nitrogen atom lead to an elongation of the C6−N bond, compared to the parent system 2.

ChemInform Abstract: A Versatile and Convenient Regioselective Acylation of 2′-Deoxynucleosides and Ribonucleosides by Supported Lipases of Pseudomonas cepacia.

Abstract Pseudomonas Cepacia lipase supported on ceramic particles (lipase PS-C) and on diatomite (lipase PS-D) regioselectively acylated 2′-deoxynucleosides and ribonucleosides to 3′-O-acetyl-2′-deoxynucleosides and 3′-O-acetyl-ribonucleosides with oxime esters in organic solvents at room temperature. This enzymatic reaction was significant because the regioselectivity was total; as any other regioisomer nor the N-acylated product were observed.

A Versatile and Convenient Regioselective Acylation of 2′-Deoxynucleosides and Ribonucleosides by Supported Lipases of Pseudomonas Cepacia

Pseudomonas Cepacia lipase supported on ceramic particles (lipase PS-C) and on diatomite (lipase PS-D) regioselectively acylated 2′-deoxynucleosides and ribonucleosides to 3′-O-acetyl-2′-deoxynucleosides and 3′-O-acetyl-ribonucleosides with oxime esters in organic solvents at room temperature. This enzymatic reaction was significant because the regioselectivity was total; as any other regioisomer nor the N-acylated product were observed.