Kinetic resolution of alpha-acetoxy N-acyl oxazolidinethiones by a chiral O-nucleophilic acyl transfer catalyst

The kinetic resolution of alpha-acetoxy N-acyl oxazolidinethiones using the chiral, nonracemic O-nucleophilic acyl transfer catalyst 8 is described. The reaction proceeds on a variety of substrates in excellent yields, with s-factors ranging from 17 to 31.     

Tight binding inhibitors of N-acyl amino sugar and N-acyl amino acid deacetylases

Very potent inhibitors were synthesized for the enzymatic deacetylation of N-acetyl-d-glucosamine-6-phosphate (NagA) and N-acetyl-d-glutamate (DGD). The methyl phosphonamidate derivative of d-glucosamine-6-phosphate bound to N-acetyl-d-glucosamine-6-phosphate deacetylase with an equilibrium dissociation constant of 34 +/- 5 nM at pH 7.5 and an association rate constant of 6.1 x 103 M-1 s-1. The inhibition constant is 4000-fold lower than the Michaelis constant for the substrate N-acetyl-d-glucosamine-6-phosphate. N-Acetyl-d-glutamate deacetylase was inhibited by the methyl phosphonamidate derivative of d-glutamate with an inhibition constant of 460 +/- 70 pM at pH 7.6. The inhibitor bound to the enzyme 500 000-fold tighter than the Michaelis constant for N-formyl-d-glutamate. These compounds mimic the putative tetrahedral intermediate formed upon nucleophilic attack of an activated water molecule on the amide bond of the target substrate. These inhibitors should prove useful in the elucidation of the enzyme-substrate interactions for enzymes within the amidohydrolase superfamily.     

N-acyl glycinates as acyl donors in serine protease-catalyzed kinetic resolution of amines. Improvement of selectivity and reaction rate

Enzymatic kinetic resolution of aliphatic and benzylic amines leading to (S)-amides was achieved by using alkaline protease as the catalyst and N-octanoyl glycine trifluoroethyl ester as the acyl donor; enantioselectivity ranged between 4 to 244, while reaction times were dramatically shortened and ranged between 15 min to 6 h.     

Subtilisin-catalyzed religation of proteolyzed hen egg-white lysozyme: investigation of the role of disulfides

Background: The use of proteases to form, instead of break, peptide bonds has expanded the repertoire of techniques available for protein semisynthesis. Several groups have previously reported the use of proteases in aqueous-organic solvents to form single amide bonds within proteins, but low yields and lengthy reaction times make this an impractical approach to protein synthesis. We recently found that proteolyzed triose phosphate isomerase can be re-ligated rapidly and efficiently by subtilisin, in mixed aqueous-organic solvent systems.Results: We now report the use of subtilisin to resynthesize hen egg-white lysozyme from a mixture of its proteolyzed fragments in high yield and with rapid reaction times. This enzymatic religation can also be achieved after reduction of the four disulfide bonds present in lysozyme, with the same efficiency as that observed for the disulfide-containing proteolysis mixture.Conclusions: For egg-white lysozyme, the subtilisin religation reaction can be used to re-synthesize a proteolyzed protein even after reduction of disulfide bonds. The utility of this reaction in more generalized protein semisynthesis reactions is currently being explored.     

Direct synthesis of polyamides by N-acyl phosphoramidites

A variety of N-acyl phosphoramidites were prepared from chlorophosphites and amide derivatives, and their structures were determined with the aid of ¹H-, ¹³C-, and ³¹P-NMR, and IR spectroscopies. These phosphoramidites were employed in direct polycondensation reaction of dicarboxylic acids and diamines under various conditions resulting in polyamides with inherent viscosities of 0.1 to 1.13. The best results were obtained when aliphatic dicarboxylic acids and aromatic diamines were condensed by 2-(N-methylacetamido)-1,3,2-dioxaphospholane in nitriles.     

N-acyl (substituted) phenylglycine derivatives

Amidoalkylation of three benzoheterocycles, benzimidazole-2-one, 1,3-dihydrobenzo[c]-thiophene 2,2-dioxide and 1,3-dihydro-2,1,3-benzothiadiazole using N-acylhippuric acids was successful. The corresponding phenylglycine analogs were prepared by removal of the N-acyl protecting group.     

Determination of fluoroquinolone antibacterials as N-acyl derivatives

Summary A simple and quantitative method for the preparation and high performance liquid chromatography (HPLC) of N-acylated fluoroquinolones has been developed. The acylation procedure was performed with four different acid anhydrides and found to be applicable to several fluoroquinolones. The acylated derivatives were chromatographed directly on a Nucleosil C₁₈ column without the necessity of further sample manipulation. Detector response for the N-acetyl derivatives of norfloxacin, ciprofloxacin, sarafloxacin, and temafloxacin was linear to at least 50 g/mL. The retention behavior of the N-acyl derivatives can be predicted by the length of the carbon chain of the amide.     

N-acyl DBN tetraphenylborate salts as N-acylating agents

Air-stable and crystalline N-acyl DBN tetraphenylborate salts have been synthesized from 1,5-diazabicyclo[4.3.0]non-5-ene (DBN) and the corresponding acyl chloride in the presence of sodium tetraphenylborate. The salts have been shown to be effective N-acylating agents, reacting with primary amines, secondary amines, and sulfonamides to form the corresponding N-acylated products in good yields. The DBN hydrotetraphenylborate byproduct can be conveniently removed by filtration, providing pure N-acylated products without the need for further purification. The N-acyl DBN tetraphenylborate salts are attractive alternatives to acyl halides as they can be stored in air without decomposition, avoid the production of free acid during acylation reactions, and can be used under more forcing thermal conditions.     

Synthesis of α-dicarbonyl compounds from N-acyl α-aminoketones

Conclusions Samples of-dicarbonyl compounds isolated in the form of dioximes or nickel complexes of these dioximes were obtained upon the bromination of N-acyl--aminoketones in isopropyl alcohol or concentrated hydrochloric acid and also of the enolacetates of N,N-diacyl--aminoketones in methanol.Translated from Izvestiya Akademii Nauk SSSR, Seriya Khimicheskaya, No. 5, pp. 1044–1048, May, 1979.     

Radical-mediated synthesis of alpha-C-glycosides based on N-acyl galactosamine

[structure] C-Glycosides of N-acyl 2-amino-2-deoxygalactose (acyl = MeCO, CF(3)CO, t-BuOCO) are available in a stereoselective manner by trapping of an anomeric radical with an activated alkene. Using anomeric selenides, radical generation and trapping is carried out under conditions that avoid competitive reduction, and this chemistry has been applied to the synthesis of the novel C-glycoside analogue of O-benzyl alpha-D-GalNAc.     

手性路易斯碱催化N-酰基烯胺不对称还原

首次利用手性哌啶酰胺类和叔丁基亚磺酰胺类路易斯碱催化三氯氢硅对N-酰基烯胺的不对称还原反应,以优良的收率(＞90%)和中等的对映选择性( 2%ee～36%ee)获得了相应的N-酰基手性胺产物.     

Chlorination of N-acyl Derivatives of p-Aminophenols (Naphthols) and p-Phenylenediamines

The chlorination of N-acyl derivatives of p-aminophenols can provide either N-acyl-2,3,6-trichloro-4-aminophenols or N-acyl-2,3,5,6-tetrachloro-1,4-benzoquinone imines depending on solvent nature, process temperature, and molar ratio initial compound-chlorine. The chlorination of N-acyl-4-amino-1-naphthols affords only N-acyl-2,3-dichloro-1,4-naphthoquinone imines. N,N'-Diacyl-1,4-phenylenediamines give rise on chlorination to a mixture of 2,5-dichloro-, 2,6-dichloro-, and 2,3-dichloro-N,N'-diacyl-1,4-phenylenediamines.     

Antibody interference with N-acyl homoserine lactone-mediated bacterial quorum sensing

Many bacterial pathogens coordinate their virulence factor expression in a cell density-dependent manner. This population-dependent coordination of gene expression in bacteria has been termed "quorum sensing" (QS). N-Acyl homoserine lactones (AHLs) are used by over 70 Gram-negative bacterial species as autoinducers. Inhibition of QS signaling might represent a new target for antimicrobial therapy. Here we report the hapten design, synthesis, generation of monoclonal antibodies (mAbs) against AHLs, and the evaluation of these mAbs for their ability to blunt QS signaling and inhibit virulence factor expression in P. aeruginosa. The mAbs can be envisioned as a tool for future investigations into AHL-based QS, which may aid in gaining new insights into the pathogenesis of P. aeruginosa and may ultimately lead to the development of new strategies to combat bacterial diseases.     

Stable N-acyl pyridinium and benzpyridinium salts as alkylating agents

The reaction of acyl chlorides with pyridinium bases and antimony pentachloride yields stable N-acyl salts that are efficient acylating agents. The kinetics of the reaction of N-acyl-pyridinium salts with p-nitroaniline was studied, and the reactivities of acylpyridinium cations and the ion pairs were determined.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 4, pp. 501–504, April, 1987.     

N-acyl triazenes as tunable and selective chemodosimeters toward cyanide ion

A novel type of chemodosimeters has been developed on the basis of a displacement reaction. N-Acyl-triazenes are found to be highly selective and tunable chemodosimeters toward cyanide. When N-acetyl-triazene 1a was titrated with various anions (-CN, F-, Cl-, AcO-, H2PO4-, -SCN, ClO4-, and HSO4-) in acetonitrile, significant absorption changes (from colorless to deep purple) resulted in the cases of -CN and F-, and small changes in the cases of AcO- and H2PO4-. N-Isopropanoyl-triazene 1b showed significant response only toward -CN, weaker response toward F-, and little response toward other anions in acetonitrile. Both of the triazenes 1a and 1b responded only to -CN in methanol-water, because of the analyte's strong nucleophilicity toward the acyl group and weak hydrogen-bonding ability as compared to other anions examined. The N-acyl-triazenes can be used for the naked eye detection of cyanide.