Cleavage Of Amide Bond Research Articles

Batch vs Continuous‐Flow Method to Synthesize N‐(3‐acylamidopropyl)lactams through N‐C Bond Cleavage in Amides with Amidines

The selective N‐C bond cleavage of amides to create value‐added products through a transition metal‐free approach has become a significant challenge. Here, we present a method to convert amides into N‐(3‐acylamidopropyl)lactams through sequential amide chemoselective N‐C bond cleavage and amidine ring opening under mild conditions, applicable in batch and continuous flow processes. These methods utilize bench‐stable reagents and are operationally straightforward and mild, enabling synthesis on a gram scale with excellent functional group tolerance. Additionally, the synthetic feasibility of these reactions under flow conditions has proven to be highly efficient, providing N‐(3‐acylamidopropyl)lactam derivatives with improved yields and shorter reaction time.

De(sulfon)amidative Cyclization: The Synthesis of Dibenzolactams and Dibenzosultams for Organic Light Emitting Diode Materials

This study addresses a challenge in organic synthetic chemistry: the direct cleavage of amide bonds, which is typically hampered by the thermodynamic stability of the C(Ar)–C(acyl) bond. Previous methods often rely on “CO” extrusion‐jointing transition metal‐catalyzed process and require activated tertiary amides, limiting their applicability due to incompatibility with reactive functional groups such as halogens. Herein, we report a transition metal‐free approach for the deamidative cyclization of biaryl diamides via a radical process, yielding dibenzolactam derivatives. Along this line, we have developed the desulfonamidative cyclization of biaryl disulfonamides to produce dibenzosultams through direct nucleophilic aromatic substitution, demonstrating high selectivity for unsymmetrical structures. Additionally, unsymmetrical sulfamoyl biaryl amides, containing both amide and sulfonamide functionalities, can selectively undergo desulfonamidative coupling with the amide to form dibenzolactams, which offers a complementary synthetic pathway to unsymmetric dibenzolactams. These protocols exhibit excellent compatibility with reactive functional groups, including halogens, providing an innovative synthetic toolbox for the development of thermally activated delayed fluorescence (TADF) materials used in organic light emitting diodes (OLEDs). DMAC‐PDO, incorporating a dibenzolactam as the acceptor unit, serves as an efficient blue TADF emitter with a maximum external quantum efficiency (EQEmax) of 23.4%.

De(sulfon)amidative Cyclization: The Synthesis of Dibenzolactams and Dibenzosultams for Organic Light Emitting Diode Materials.

This study addresses a challenge in organic synthetic chemistry: the direct cleavage of amide bonds, which is typically hampered by the thermodynamic stability of the C(Ar)-C(acyl) bond. Previous methods often rely on "CO" extrusion-jointing transition metal-catalyzed process and require activated tertiary amides, limiting their applicability due to incompatibility with reactive functional groups such as halogens. Herein, we report a transition metal-free approach for the deamidative cyclization of biaryl diamides via a radical process, yielding dibenzolactam derivatives. Along this line, we have developed the desulfonamidative cyclization of biaryl disulfonamides to produce dibenzosultams through direct nucleophilic aromatic substitution, demonstrating high selectivity for unsymmetrical structures. Additionally, unsymmetrical sulfamoyl biaryl amides, containing both amide and sulfonamide functionalities, can selectively undergo desulfonamidative coupling with the amide to form dibenzolactams, which offers a complementary synthetic pathway to unsymmetric dibenzolactams. These protocols exhibit excellent compatibility with reactive functional groups, including halogens, providing an innovative synthetic toolbox for the development of thermally activated delayed fluorescence (TADF) materials used in organic light emitting diodes (OLEDs). DMAC-PDO, incorporating a dibenzolactam as the acceptor unit, serves as an efficient blue TADF emitter with a maximum external quantum efficiency (EQEmax) of 23.4%.

Gold(III)-Induced Amide Bond Cleavage In Vivo: A Dual Release Strategy via π-Acid Mediated Allyl Substitution.

Selective cleavage of amide bonds holds prominent significance by facilitating precise manipulation of biomolecules, with implications spanning from basic research to therapeutic interventions. However, achieving selective cleavage of amide bonds via mild synthetic chemistry routes poses a critical challenge. Here, we report a novel amide bond-cleavage reaction triggered by Na[AuCl4] in mild aqueous conditions, where a crucial cyclization step leads to the formation of a 5-membered ring intermediate that rapidly hydrolyses to release the free amine in high yields. Notably, the reaction exhibits remarkable site-specificity to cleave peptide bonds at the C-terminus of allyl-glycine. The strategic introduction of a leaving group at the allyl position facilitated a dual-release approach through π-acid catalyzed substitution. This reaction was employed for the targeted release of the cytotoxic drug monomethyl auristatin E in combination with an antibody-drug conjugate in cancer cells. Finally, Au-mediated prodrug activation was shown in a colorectal zebrafish xenograft model, leading to a significant increase in apoptosis and tumor shrinkage. Our findings reveal a novel metal-based cleavable reaction expanding the utility of Au complexes beyond catalysis to encompass bond-cleavage reactions for cancer therapy.

A General Method to Access Underexplored Ylideneamino Sulfates as Interrupted Beckmann-Type Rearrangement Intermediates.

The Beckmann rearrangement of ketoximes to their corresponding amides, using a Brønsted acid-mediated fragmentation and migration sequence, has found wide-spread industrial application. We postulated that the development of a methodology to access ylideneamino sulfates using tributylsulfoammonium betaine (TBSAB) would afford isolable Beckmann-type intermediates and competent partners for subsequent rearrangement cascades. The ylideneamino sulfates generated, isolated as their tributylammonium salts, are sufficiently activated to undergo Beckmann rearrangement without additional reagent activation. The generation of sulfuric acid in situ from the ylideneamino sulfate giving rise to a routine Beckmann rearrangement and additional amide bond cleavage to the corresponding aniline was detrimental to reaction success. The screening of bases revealed inexpensive sodium bicarbonate to be an effective additive to prevent classic Brønsted acid-mediated fragmentation and achieve optimal conversions of up to 99%.

Bio-based, closed-loop chemical recyclable aromatic polyamide from 2,5-furandicarboxylic acid: Synthesis, high performances, and degradation mechanism

The resource and environmental challenges posed by the extensive use and disposal of plastics have increased the urgency of research into plastic recycling and the hunt for bio-based alternative feedstocks. As one of the five general engineering polymers, polyamide has not yet been systematically explored in terms of its recycling performance or mechanism, especially aromatic polyamides. In addition, research on novel structured bio-based aromatic polyamides has not received sufficient attention due to the harsh polymerization conditions. In this work, bio-based fully aromatic polyamides based on 2,5-furandicarboxylic acid (FDCA) was successfully synthesized through the acyl chloride method, exhibiting thermal, mechanical, and barrier properties comparable to or superior to those of fossil derived isophthalic acid based polyamides. Moreover, both synthesized polyamides could be hydrolyzed in alkaline environments through the cleavage of amide bonds, as demonstrated by molecular dynamics simulations. The presence of furan rings lowered the energy barrier of hydrolysis as compared to benzene rings. Furthermore, a simple and efficient acidification followed by filtration approach with high recovery yields was developed to recover initial monomers from degradation solutions, thus achieving closed-loop chemical recovery of two polyamides. This work will further expand the application of bio-based feedstock, FDCA, and open new avenues for polyamide recycling research.

Exploring Aqueous Coordination Chemistry of Highly Lewis Acidic Metals with Emerging Isotopes for Nuclear Medicine.

Nuclear medicine harnesses radioisotopes for the diagnosis and treatment of disease. While the isotopes 99mTc and 111In have enabled the clinical diagnosis of millions of patients over the past 3 decades, more recent clinical translation of numerous 68Ga/177Lu-based radiopharmaceuticals for diagnostic imaging and therapy underscores the clinical utility of metal-based radiopharmaceuticals in mainstream cancer treatment. In addition to such established radionuclides, advancements in radioisotope production have enabled the production of radionuclides with a broad range of half-lives and emission properties of interest for nuclear medicine. Chemical means to form kinetically inert, in vivo-compatible species that can be modified with disease-targeting vectors is imperative. This presents a challenge for radiosiotopes of elements where the aqueous chemistry is still underdeveloped and poorly understood. Here, we discuss our efforts to date in exploring the aqueous, radioactive coordination chemistry of highly Lewis acidic metal ions and how our discoveries apply to the diagnosis and treatment of cancer in preclinical models of disease. The scope of this Account includes approaches to aqueous coordination of to-date understudied highly Lewis acidic metal ions with radioisotopes of emerging interest and the modulation of well-understood coordination environments of radio-coordination complexes to induce metal-catalyzed reactivity for separation and pro-drug applications.First, we discuss the development of seven-coordinate, small-cavity macrocyclic chelator platform mpatcn/picaga as an exemplary case study, which forms robust complexes with 44Sc/47Sc isotopes. Due to the high chemical hardness and pronounced Lewis acidity of the Sc3+ ion, the displacement of ternary ligand H2O by 18/natF- can be achieved to form an inert Sc-18/natF bond. Corresponding coordination complex natSc-18F is in vivo compatible and forms a theranostic tetrad with corresponding 44Sc/47Sc, 177Lu complexes all exhibiting homologous biodistribution profiles. Another exceptionally hard, highly Lewis acidic ion with underdeveloped aqueous chemistry and emerging interest in nuclear medicine is 45Ti4+. To develop de novo approaches to the mononuclear chelation of this ion under aqueous conditions, we employed a fragment-based bidentate ligand screening approach which identified two leads. The screen successfully predicted the formation of [45Ti][Ti(TREN-CAM)], a Ti-triscatechol complex that exhibits remarkable in vivo stability. Furthermore, the fragment-based screen also identified approaches that enabled solid-phase separation of Ti4+ and Sc3+ of interest in streamlining the isotope production of 45Ti and accessing new ways to separate 44Ti/44Sc for the development of a long-lived generator system. In addition to establishing the inert chelation of Ti4+ and Sc3+, we introduce controlled, metal-induced reactivity of corresponding coordination complexes on macroscopic and radiotracer scales. Metal-mediated autolytic amide bond cleavage (MMAAC) enables the temperature-dependent release of high-molar-activity, ready-to-inject radiopharmaceuticals; cleavage is selectively triggered by coordinated trivalent Lewis acid nat/68Ga3+ or Sc3+. Following the scope of reactivity and mechanistic studies, we validated MMAAC for the synthesis of high-molar-activity radiopharmaceuticals to image molecular targets with low expression and metal-mediated prodrug hydrolysis in vivo.This Account summarizes how developing the aqueous coordination chemistry and tuning the chemical reactivity of metal ions with high Lewis acidity at the macroscopic and tracer scales directly apply to the radiopharmaceutical synthesis with clinical potential.

Photochemical transformation of a perylene diimide derivative beneficial for thein situformation of a molecular photocatalyst of the hydrogen evolution reaction

Photochemical cleavage of amide bonds of the perylene diimide derivative in the presence of Pt2+cations affords HER-active photocatalyst, whose efficiency is the highest in the micellar nanoparticle form.

Evaluation of functional group compatibility and development of reaction-accelerating additives in ammonium salt-accelerated hydrazinolysis of amides.

Functional group compatibility in an amide bond cleavage reaction with hydrazine was evaluated for 26 functional groups in the functional group evaluation (FGE) kit. Accurate and rapid evaluation of the compatibility of functional groups, such as nitrogen-containing heterocycles important in drug discovery research, will enhance the application of this reaction in drug discovery research. These data will be used for predictive studies of organic synthesis methods based on machine learning. In addition, these studies led to discoveries such as the unexpected positive additive effects of carboxylic acids, indicating that the FGE kit can propel serendipitous discoveries.

C−C Bond Cleavage of α‐Pyridinium Amides: A Synthetic Approach to Hydantoin Structures

AbstractThis study reports a mild reaction‐condition approach for the direct C−C bond cleavage of amides to form hydantoin structures in the presence of 4‐methylpyridine and a base. This approach presents an amide C−C bond cleavage strategy enabling nucleophilic addition to the amide carbonyl involving a reactive spiro intermediate. A broad spectrum of pseudo peptide Ugi adducts as bifunctional starting materials was synthesized and used in this transformation. The mechanistic pathway of this reaction was investigated using experimental and theoretical studies.

Metal-Mediated, Autolytic Amide Bond Cleavage: A Strategy for the Selective, Metal Complexation-Catalyzed, Controlled Release of Metallodrugs.

Activation of metalloprodrugs or prodrug activation using transition metal catalysts represents emerging strategies for drug development; however, they are frequently hampered by poor spatiotemporal control and limited catalytic turnover. Here, we demonstrate that metal complex-mediated, autolytic release of active metallodrugs can be successfully employed to prepare clinical grade (radio-)pharmaceuticals. Optimization of the Lewis-acidic metal ion, chelate, amino acid linker, and biological targeting vector provides means to release peptide-based (radio-)metallopharmaceuticals in solution and from the solid phase using metal-mediated, autolytic amide bond cleavage (MMAAC). Our findings indicate that coordinative polarization of an amide bond by strong, trivalent Lewis acids such as Ga3+ and Sc3+ adjacent to serine results in the N, O acyl shift and hydrolysis of the corresponding ester without dissociation of the corresponding metal complex. Compound [68Ga]Ga-10, incorporating a cleavable and noncleavable functionalization, was used to demonstrate that only the amide bond-adjacent serine effectively triggered hydrolysis in solution and from the solid phase. The corresponding solid-phase released compound [68Ga]Ga-8 demonstrated superior in vivo performance in a mouse tumor model compared to [68Ga]Ga-8 produced using conventional, solution-phase radiolabeling. A second proof-of-concept system, [67Ga]Ga-17A (serine-linked) and [67Ga]Ga-17B (glycine-linked) binding to serum albumin via the incorporated ibuprofen moiety, was also synthesized. These constructs demonstrated that complete hydrolysis of the corresponding [68Ga]Ga-NOTA complex from [67Ga]Ga-17A can be achieved in naïve mice within 12 h, as traceable in urine and blood metabolites. The glycine-linked control [68Ga]Ga-17B remained intact. Conclusively, MMAAC provides an attractive tool for selective, thermal, and metal ion-mediated control of metallodrug activation compatible with biological conditions.

Dinuclear platinum(II) complexes with 1,5-nphe bridging ligand: Spectroscopic and molecular docking study of the interactions with N-acetylated L-methionylglycine and human serum albumin

The hydrolysis of N-acetylated L-methionylglycine dipeptide (Ac-L-Met-Gly) in the presence of dinuclear platinum(II)-aqua complexes with general formula [{Pt(L)(H2O)}2(μ-1,5-nphe)]4+ (1,5-nphe is 1,5-naphthyridine; L is bidentately coordinated ethylenediamine (1w), (±)-1,2-propylenediamine (2w) and 1,3-propylenediamine (3w)) is described in detail. The hydrolytic activity of these complexes was monitored by 1H NMR spectroscopy, which confirmed the regioselective cleavage of the Met-Gly-amide bond in this peptide. Quantum-chemical calculations revealed the primary reaction path with coordination of dipeptide via the terminal amide nitrogen of methionine followed by its coordination for the sulphur atom, in which the decomposition of the resulted platinum(II)-dipeptide complex and the coordination of its glycine residue precedes the hydrolytic cleavage of the Met-Gly amide bond. In the secondary reaction path, in which Ac-L-Met-Gly is coordinated via the methionine sulphur atom, the decomposition of the starting [{Pt(L)(H2O)}2(μ-1,5-nphe)]4+ complex is followed by the regioselective hydrolysis of the investigated dipeptide. The binding affinity of the chloride derivatives of the corresponding dinuclear platinum(II)-aqua complexes, [{Pt(L)Cl}2(μ-1,5-nphe)]2+ (1–3) towards the human serum albumin (HSA), a transport protein, was investigated using electronic absorption and fluorescence emission measurements, and results indicated the static interactions between these complexes and HSA. A docking study revealed a unique binding site on HSA, based on the electrostatic and the hydrogen bonding, which does not have a methionine residue nearby, therefore does not exist danger of HSA hydrolysis by these complexes.

Metal-Organic Bichromophore Lowers the Upconversion Excitation Power Threshold and Promotes UV Photoreactions.

Sensitized triplet-triplet annihilation upconversion is a promising strategy to use visible light for chemical reactions requiring the energy input of UV photons. This strategy avoids unsafe ultraviolet light sources and can mitigate photo-damage and provide access to reactions, for which filter effects hamper direct UV excitation. Here, we report a new approach to make blue-to-UV upconversion more amenable to photochemical applications. The tethering of a naphthalene unit to a cyclometalated iridium(III) complex yields a bichromophore with a high triplet energy (2.68 eV) and a naphthalene-based triplet reservoir featuring a lifetime of 72.1 μs, roughly a factor of 20 longer than the photoactive excited state of the parent iridium(III) complex. In combination with three different annihilators, consistently lower thresholds for the blue-to-UV upconversion to crossover from a quadratic into a linear excitation power dependence regime were observed with the bichromophore compared to the parent iridium(III) complex. The upconversion system composed of the bichromophore and the 2,5-diphenyloxazole annihilator is sufficiently robust under long-term blue irradiation to continuously provide a high-energy singlet-excited state that can drive chemical reactions normally requiring UV light. Both photoredox and energy transfer catalyses were feasible using this concept, including the reductive N-O bond cleavage of Weinreb amides, a C-C coupling reaction based on reductive aryl debromination, and two Paternò-Büchi [2 + 2] cycloaddition reactions. Our work seems relevant in the context of developing new strategies for driving energetically demanding photochemistry with low-energy input light.

Radiolysis of diamide phenanthroline extractant: exploring the mechanism of HNO3 enhancing the extraction and An/Ln separation performance after irradiation

The stability of organic extractant molecules against radiolysis is critical in the field of actinides and lanthanides (An/Ln) separations. In order to evaluate the radiolytic effects on the extraction performance, the solutions of N,N’-diethyl-N,N’-ditolyl-2,9-diamide-1,10-phenanthroline (Et-Tol-DAPhen) in n-octanol were subjected to γ-irradiation in the presence and absence of 3 mol/L HNO3 aqueous phase. Et-Tol-DAPhen diluted in n-octanol was almost completely decomposed after irradiation and exhibits decreased extraction ability at an absorbed dose of about 384 kGy, along with the appearance of various degradation products. Et-Tol-DAPhen, which was diluted in n-octanol, was completely decomposed upon irradiation in the presence of 3 mol/L HNO3 aqueous phase. However, it exhibited higher DU and SFU/Eu values than before irradiation, as well as degradation products that were also generated. The structures of some isomers of radiolytic products were investigated by density functional theory (DFT) calculations, the radiolysis pathways and products of Et-Tol-DAPhen extractants were obtained, and the radiolysis pathways and products of Et-Tol-DAPhen extractants was proposed. The radiolytic products mainly originated from amide bond and NC bond cleavage of side group substituents, and some resulted from interaction with n-octanol radicals generated during radiolysis. The presence of HNO3 can inhibit the radiolysis of Et-Tol-DAPhen to a certain extent and cause enhanced extraction ability. Moreover, the DFT calculations reveal that the radiolytic products produced in presence of 3 mol/L HNO3 aqueous phase also have efficient extraction performance towards UO22+. The understanding of the radiolysis pathways and products of extractants, based on radiation chemical effects is expected to be helpful for developing new strategies for extractants with long-term performance.

Lysosome-targeting phenalenones as efficient type I/II photosensitizers for anticancer photodynamic therapy

Development of safe and effective photosensitizers is important for enhancing the efficacy of photodynamic cancer therapy. Phenalenone is a type II photosensitizer with a high singlet oxygen quantum yield; however, its short UV absorption wavelength hinders its application in cancer imaging and in vivo photodynamic therapy. In this study, we report a new redshift phenalenone derivative, 6-amino-5-iodo-1H-phenalen-1-one (SDU Red [SR]), as a lysosome-targeting photosensitizer for triple-negative breast cancer therapy. SDU Red produced singlet oxygen (Type II reactive oxygen species [ROS]) and superoxide anion radicals (Type I ROS) upon light irradiation. It also exhibited good photostability and a remarkable phototherapeutic index (PI > 76) against triple-negative breast cancer MDA-MB-231 cancer cells. Additionally, we designed two amide derivatives, SRE-I and SRE-II, with decreased fluorescence and photosensitizing capabilities based on SDU Red as activatable photosensitizers for photodynamic cancer therapy. SRE-I and SRE-II could be further converted into the active photosensitizer SDU Red via carboxylesterase-catalyzed amide bond cleavage. Moreover, SDU Red and SRE-II induced DNA damage and cell apoptosis in the presence of light. Therefore, SRE-II can act as a promising theranostic agent for triple-negative breast cancer.

Probing Unexpected Reactivity in Radiometal Chemistry: Indium-111-Mediated Hydrolysis of Hybrid Cyclen-Hydroxypyridinone Ligands

Chelators based on hydroxypyridinones have utility in incorporating radioactive metal ions into diagnostic and therapeutic agents used in nuclear medicine. Over the course of our hydroxypyridinone studies, we have prepared two novel chelators, consisting of a cyclen (1,4,7,10-tetraazacyclododecane) ring bearing two pendant hydroxypyridinone groups, appended via methylene acetamide motifs at either the 1,4-positions (L1) or 1,7-positions (L2) of the cyclen ring. In radiolabeling reactions of L1 or L2 with the γ-emitting radioisotope, [111In]In3+, we have observed radiometal-mediated hydrolysis of a single amide group of either L1 or L2. The reaction of either [111In]In3+ or [natIn]In3+ with either L1 or L2, in aqueous alkaline solutions at 80 °C, initially results in formation of [In(L1)]+ or [In(L2)]+, respectively. Over time, each of these species undergoes In3+-mediated hydrolysis of a single amide group to yield species in which In3+ remains coordinated to the resultant chelator, which consists of a cyclen ring bearing a single hydroxypyridinone group and a single carboxylate group. The reactivity toward hydrolysis is higher for the L1 complex compared to that for the L2 complex. Density functional theory calculations corroborate these experimental findings and importantly indicate that the activation energy required for the hydrolysis of L1 is significantly lower than that required for L2. This is the first reported example of a chelator undergoing radiometal-mediated hydrolysis to form a radiometalated complex. It is possible that metal-mediated amide bond cleavage is a source of instability in other radiotracers, particularly those in which radiometal complexation occurs in aqueous, basic solutions at high temperatures. This study highlights the importance of appropriate characterization of radiolabeled products.

Insight into the synergistic reaction mechanism of biomass pseudocomponents and polyamide by TG-MS and Py-GC/MS: Pyrolysis properties, reaction kinetics and N-containing species evolution

To unveil the nitrogen migration and conversion characteristics, catalytic copyrolysis of biomass pseudo components and polyamide (PA) with different blend ratios (1:0, 5:1, 3:1, 1:1, 1:3, 1:5, 0:1) under an ammonia atmosphere was proposed to boost the yield of N-containing compounds (NCCs) and N-rich biochar. The evolution and distribution of NCCs in liquid, gas and biochar were systematically investigated with a combination of TG-MS, Py-GC/MS and EPR. Synergistic effects and possible reaction pathways were also evaluated. Experimental results showed that PA could obviously boost biomass conversion due to increasing the chance of secondary cleavage, and the comprehensive synergistic effect of biomass-derived H* radicals, acid sites of the catalyst and cracking reactions (-C-N and C-C bonds) that reduced the reaction energy barrier and enhanced the NH3 and HCN yields. NH3 comes from the amino acids that are released from the amino acid pyrolysis and hydrolysis of HCN on the surface of char, while HCN is from the secondary cracking of primary pyrolysis products. Adding biomass increased CO2, CO, CH4, C-O and CO emissions from co-pyrolysis. Additionally, significant synergetic effects were observed when Biomass/PA= 3:1, which improved the NCCs and pyridine yields by 78.58% and 48.23%, respectively, under the HZSM-5 catalyst. A lower proportion of PA addition facilitated the Maillard reaction and amide bond cleavage to enhance the NCCs content and suppressed π-conjugated ring structure compound evolution and coke-derived O-containing compound polymerization, while a higher content of PA was favorable for amine and diaza heterocycle compound formation. Moreover, the addition of PA reduced the HHV and N content in biochar, resulting in lower pyrrole-N content and graphitization degree due to secondary cross-polymerization reaction of reaction volatiles, but it enhanced the polarity due to higher oxygen content (14.98%).

Homogeneous preparation of water-soluble products from chitin under alkaline conditions and their cell proliferation in vitro

The purpose of this study was to prepare water-soluble products by homogeneous depolymerization of chitin with H2O2 under alkaline conditions and investigate their potential application in wound healing. For the first time, water-soluble products were successfully prepared using a chitin-NaOH/urea solution; the products were chitosans with molecular weights (Mw) of 3.48–33.5 kDa and degrees of deacetylation (DD) > 0.5. Their Mw, DD and yield were affected by the reaction temperature, reaction time, concentration of H2O2 and chitin DD. The deacetylation and depolymerization of chitin were achieved simultaneously. The depolymerization of chitin was caused by hydrogen abstraction of HO, whereas the deacetylation resulted from the cleavage of amide bonds by HO− and HO2−, although the latter played a more important role. All water-soluble chitosans markedly promoted the proliferation of human skin fibroblast (HSF) cells, but they inhibited the proliferation of human keratinocyte cells. For the proliferation of HSF, a low concentration of chitosans was important. In addition, water-soluble chitosans with an Mw of 3.48–16.4 kDa markedly stimulated the expression of growth factors such as PDGF and TGF-β by macrophages. Water-soluble chitosans could be used as a potential active component in wound dressings.

Research progress on transition-metal-free C–N bonds cleavage of amides in the synthesis of ketones

<p indent="0mm">Amides compounds have a wide range of application, and many transforming strategies have been reported. Transition metals-catalyzed non-decarbonylative cross-coupling reaction of amides has gained considerable attention due to low cost, high efficiency, and good compatibility of functional groups. The reactions have following disadvantages due to the inherent nature of catalytic system: expensive catalysts, complex ligands, cocatalysts and trace metals residues. The transition-metal-free amide activation strategies for synthesis of ketones avoid the above problems with high efficiency and simple treatment. From the perspective of sustainable development, the development of amide activation strategy without transition metals has great significance. In this paper, the synthesis of ketones by C–N bond cleavage of amides without transition metals were reviewed. The main contents as follows: (1) synthesis of ketones by direct addition of alkali metal/alkaline-earth metal reagents to amides; (2) the Brønsted base-promoted non-decarbonylative cross-coupling reaction of amides and alkanes with activated groups; (3) synthesis of ketones by cleavage of amide C–N bond based on activation strategy; (4) acid-promoted Friedel-Crafts acylation reaction of amide; (5) Lewis acid-promoted the non-decarbonylative cross-coupling reaction between amide and alkyl ketone. This review provides inspiration for the subsequent development of economic and green amide activation reaction.

Rapid cleavage of amide bond in proline-based nucleotripeptides

Unexpected fragmentation reactions of tripeptides H-Pro-Hyp[CH2(R)]-Pro-OBn (R = cytosine (Boc) or uracil) to afford diketopiperazine (DKP) were investigated. Although peptide fragmentation to DKP has not been observed in N-terminal unprotected triproline esters, these tripeptides containing nucleobase underwent unexpected amide cleavage. The nucleobase at the second proline unit of the tripeptide was found to create an internal hydrogen bonding environment around the tripeptide. This increased the cis-state population and the basicity of the N-terminus proline nitrogen of the tripeptide, thus accelerating the unexpected amide cleavage.