Copper-mediated C-N bond formation via direct aminolysis of dithioacetals

Mediated by copper acetate, an efficient approach to the C-N bond formation via direct aminolysis of dithioacetals 2 and 5 with ammonia, primary or secondary amines are developed under mild conditions. Enaminones 3 and 6 were thus obtained in high to excellent yields with high chemoselectivity. This type of aminolysis reaction presents a new synthetic application of the dithioacetal functionality. [reaction: see text]     

Mechanism for acetic acid-catalyzed ester aminolysis

A computational study is described to elucidate the mechanism for acetic acid-catalyzed ester aminolysis to produce amides. A concerted acyl substitution mechanism is proposed to involve concurrent acyl-O bond cleavage and acyl-N bond formation where acetic acid acts as a bifunctional catalyst connecting to both the alkoxide and the amino moieties. This mechanism does not involve the intermediacy of a tetraheral adduct nor the rehybridization of acyl carbon, in sharp contrast to classic stepwise acyl substitution mechanism.     

A facile and efficient method for the synthesis of novel pyridone analogues by aminolysis of an ester under solvent-free conditions

A series of 15 pure novel N-alkylated pyridone derivatives have been synthesized in 73-96% yields on treatment of ethyl (2-pyridone)acetates with structurally diverse amines in an efficient aminolysis procedure under ‘solvent-free’ conditions.     

Kinetic and computational studies on aminolysis of bicyclic carbonates bearing alicyclic structure giving alicyclic hydroxyurethanes

Aminolysis of bicyclic carbonates, which consist of five-membered cyclic carbonate and five- or six-membered alicyclic groups, was examined. Kinetic studies revealed that the aminolysis of the bicyclic carbonate with cyclohexane ring proceeded more smoothly than that of the bicyclic carbonate with cyclopentane ring. Computational calculation suggested that the different reaction rates originate from the distinct ring-strain of the cyclic carbonate groups affected by the conformation of the alicyclic groups.     

Rate enhancement of PFP sulfonate ester aminolysis by chloride salts in organic and aqueous media

We report here, a method of accelerating the rate of aminolysis of PFP sulfonates to yield sulfonamides using tetrabutylammonium salts. We have previously explored the utility of employing PFP sulfonates in the formation of sulfonamides; however we demonstrate here the advantages of combining the existing methodology with a revised protocol which allows the diversity within both the sulfonate ester and the amine to be extended.     

Fluorinated Glycosyl Amino Acids for Mucin‐Like Glycopeptide Antigen Analogues

The aberrant glycosylation profiles of mucin glycoproteins on epithelial tumour cells represent attractive target structures for the development of immunotherapy against cancer. Mucin‐type glycopeptides have been successfully investigated as molecularly defined vaccine prototypes for triggering humoral immunity but are susceptible to rapid in vivo degradation. As a potential means to enhance the bioavailabilities of the antigenic structures, hydrolysis‐resistant carbohydrate analogues with fluorine substituents at positions C6, C2′ and C6′ were synthesised and incorporated into the tandem repeat sequence of the mucin MUC1. The resulting pseudo‐glycopeptides can be used to elucidate the effects of chemically modified antibody determinants on metabolic and immunological properties.     

A convenient aminolysis of esters catalyzed by 1,5,7-triazabicyclo[4.4.0]dec-5-ene (TBD) under solvent-free conditions

Aminolysis of esters by using the organocatalyst 1,5,7-triazabicyclo[4.4.0]dec-5-ene (TBD) is reported. Secondary and tertiary amides were synthesized from alkyl or aryl esters with a variety of primary and secondary amines in good to excellent yields (60-94%) under solvent-free conditions (SFC).     

A Fully Synthetic Glycopeptide Antitumor Vaccine Based on Multiple Antigen Presentation on a Hyperbranched Polymer

For antitumor vaccines both the selected tumor‐associated antigen, as well as the mode of its presentation, affect the immune response. According to the principle of multiple antigen presentation, a tumor‐associated MUC1 glycopeptide combined with the immunostimulating T‐cell epitope P2 from tetanus toxoid was coupled to a multi‐functionalized hyperbranched polyglycerol by “click chemistry”. This globular polymeric carrier has a flexible dendrimer‐like structure, which allows optimal antigen presentation to the immune system. The resulting fully synthetic vaccine induced strong immune responses in mice and IgG antibodies recognizing human breast‐cancer cells.     

Kinetics of the aminolysis and hydrolysis of alkyl nitrites: Evidence for an orbital controlled mechanism

Summary The kinetics of the nitrosation of piperidine by propyl,iso-propyl, butyl,iso-butyl,sec-butyl, andtert-butyl nitrites in 0.1M NaOH and of the hydrolysis of the nitrite esters were studied spectrophotometrically by monitoring the absorbance of the nitrites at 381 nm. The observed correlation between logk ₂ and * (*=4.5) shows the reaction to proceedvia electrophilic attack by the nitrites; the existence of an isokinetic relationship suggests a single mechanism for the whole series. Comparison of the relative reactivities of the alkyl nitrites (primary>secondary>tertiary) with characteristic parameters of theirR groups (vertical ionization potentials and heats of formation ofR ⁺) suggests that these reactions are orbital controlled. All hydrolysis reactions were slower than the corresponding aminolysis reactions. This is attributed to a retardation of the former reaction by unfavourable interactions between the lone pairs of the nucleophile and the nitroso nitrogen atom.

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Kinetik der Aminoloyse und Hydrolyse von Alkylnitriten: Hinweise auf einen orbitalkontrollierten Mechanismus

Zusammenfassung Die Kinetik der Nitrosierung von Piperidin durch Propyl-,iso-Propyl-, Butyl-,iso-Butyl-,sec-Butyl- undtert-Butylnitrit sowie die Hydrolyse der entsprechenden Nitritester wurde in alkalischem Medium (NaOH, 0.1M) spektrophotometrisch (=381 nm) untersucht. Die beobachtete Relation zwischen logk ₂ und * (*=4.5) zeigt, daß die Reaktion durch nucleophile Attacke des Amines erfolgt. Die Existenz einer isokinetischen Relation läßt einen einheitlichen Mechanismus für die gesamte untersuchte Serie vermuten. Aus dem Vergleich der gefundenen Reaktivitätssequenzen für die Alkylnitrite (primär>sekundär>tertiär) mit den strukturellen Parametern ihrer ResteR (Ionisationspotentiale, Bildungswärme vonR ⁺) schließen wir, daß die untersuchten Reaktionen orbitalkontrolliert verlaufen. In allen Fällen wurde bei gleichen Bedingungen eine im Vergleich zur Aminolyse entsprechend langsamere Hydrolyse beobachtet. Der Unterschied ist einer ungünstigen Wechselwirkung zwischen den einsamen Elektronenpaaren der Nucleophile und des Stickstoffatoms der NO-Gruppe während der Reaktion mit der OH^–-Gruppe zuzuschreiben.

     

The substituent effects of the leaving groups on the aminolysis of phenyl acetates: DFT studies

The density functional theory B3LYP/6-31G(d, p) method is employed to study the mechanism of aminolysis reaction of p-substituted phenyl acetates (CH₃C(O)OC₆H₄X, X = H, NH₂, and NO₂) with ammonia in the gas phase. Two reaction pathways are considered: the concerted process and the stepwise pathway through neutral intermediates. The substituent effects of the leaving groups on the reactivity of phenyl acetates are discussed. The solvent effect of acetonitrile on the title reaction is also assessed by the polarizable continuum model (CPCM model) at B3LYP/6-31++G(d, p) level of theory. The calculated results show that the activation barriers of the concerted pathways are lower than those of the rate-controlling steps of the stepwise processes for all the three aminolysis reactions. This aminolysis of phenyl acetates is more favorable for X = NO₂ than for X = H and NH₂ in the gas phase and in acetonitrile.     

A Synthetic Glycopeptide Vaccine for the Induction of a Monoclonal Antibody that Differentiates between Normal and Tumor Mammary Cells and Enables the Diagnosis of Human Pancreatic Cancer

In studies within the realm of cancer immunotherapy, the synthesis of exactly specified tumor‐associated glycopeptide antigens is shown to be a key strategy for obtaining a highly selective biological reagent, that is, a monoclonal antibody that completely differentiates between tumor and normal epithelial cells and specifically marks the tumor cells in pancreas tumors. Mucin MUC1, which is overexpressed in many prevalent cancers, was identified as a promising target for this strategy. Tumor‐associated MUC1 differs significantly from that expressed by normal cells, in particular by altered glycosylation. Structurally defined tumor‐associated MUC1 cannot be isolated from tumor cells. We synthesized MUC1–glycopeptide vaccines and analyzed their structure–activity relationships in immunizations; a monoclonal antibody that specifically distinguishes between human normal and tumor epithelial cells was thus generated.     

Efficient solvent-free aminolysis of epoxides under (C4H12N2)2[BiCl6]Cl·H2O catalysis

An efficient and rapid procedure for ring opening of various epoxides with aromatic, aliphatic and heterocyclic amines is developed at room temperature under solvent-free conditions in the presence of (C₄H₁₂N₂)₂[BiCl₆]Cl·H₂O (1 mol %). This catalyst can be reused several times without losing of its activity.     

Oligosaccharide-peptide ligation of glycosyl thiolates with dehydropeptides: synthesis of S-linked mucin-related glycopeptide conjugates

A chemoselective strategy for oligosaccharide-peptide ligation is described in which alpha-thio analogues of mucin-related glycoconjugates can be readily accessed through site-selective conjugate addition of complex oligosaccharide thiolates to dehydroalanine-containing peptides. The efficiency of the ligation is highlighted by the rapid convergent assembly of thio-isosteres of the four tumor-associated carbohydrate antigens, T(N), T, ST(N), and 2,6-ST, as a pair of diastereoisomers at the newly formed cysteine stereocenter. The process proceeds in high yield and with complete retention of the alpha-anomeric configuration.     

Additive-free porous assemblies of Ti_3C_2T_x by freeze-drying for high performance supercapacitors

Ti_3C_2T_x has shown great potential in energy storage filed,but the restacking between Ti_3C_2T_x nanosheets seriously hampers the maximization of its capacitance.In this study,we rationally designed and synthesized porous Ti_3C_2T_x assemblies without any additive by introducing ice as spacers using a facile freeze-drying method.The porous Ti_3C_2T_x assemblies have a three-dimensional network structure,which consists of ultra large Ti_3C_2T_x lamellar walls and lots of macro-and mesopores.It has been proven that there are more-O groups on the surface of the porous Ti_3C_2T_x assemblies than the Ti_3C_2T_x film.The porous Ti_3C_2T_x assemblies deliver a maximum areal capacitance of 1668 mF/cm2 when the mass loading is 8.4 mg/cm2,an optimized specific capacitance of 247.2 F/g when the mass loading is 5.3 mg/cm2,and87% capacitance retention over 10000 cycles.The symmetric solid-state supercapacitors based on the porous Ti_3C_2T_x assemblies show an areal capacitance of 355.8 mF/cm2,the maximum power density of50 mW/cm2 and an outstanding flexibility under different deformation.     

Facile synthesis of CF3-substituted dienamides via one-pot tandem reactions

A one-pot reaction sequence of sequential phosphine-promoted tandem annulations of aryl trifluoromethyl ketones and MBH (Morita-Baylis-Hillman) carbonates and DBU-mediated aminolysis was developed. This method provides a step-economical approach to trifluoromethylated dienamides with diverse structural complexity from readily available starting materials in moderate yields.     

Synthesis of α-di or trisubstituted (tetrahydrofuran-2-yl)methanols via photoinduced additive-free intermolecular addition of THF to aromatic aldehydes or ketones

THF is found to react with aromatic aldehydes or ketones highly chemoselectively under the irradiation of ultraviolet without any additives, which provides a new protocol to access α-di or trisubstituted (tetrahydrofuran-2-yl)methanols. The scope of this reaction is well studied.     

Enzymatic synthesis of N-acylethanolamines: direct method for the aminolysis of esters

Immobilized Candida antarctica (Novozyme 435) catalyzed synthesis of N-acylethanolamines is described. Treatment of methyl esters with lipase and amines yielded the desired amides within 2-24 h with yields ranging from 41% to 98%.     

Semi-synthesis of biotin-bearing activity-based ubiquitin probes through sequential enzymatic ligation,N-S acyl transfer and aminolysis reaction

Activity-based Ubiquitin probes (Ub-ABPs) carrying a reporter group have emerged as effective tools for the investigation of deubiquitinating enzymes (DUBs), such as studying the molecular mechanism of DUBs, profiling new DUBs. But so far, the synthesis of commonly used biotin-bearing Ub-ABPs is a technical challenge. Here, we report a one-pot semi-synthetic strategy for the acquiring of Ub-ABPs carrying a biotin tag through sequential enzymatic ligation, N-S acyl transfer and aminolysis reaction without any purification steps. These probes enable to capture the different family of DUBs for enrichment and immunoblotting using the attached biotin tag.