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Herein, the vitamin K2 (VK2)/maleimide (MA) coloaded mesoporous silica nanoparticles (MSNs), functional molecules including folic acid (FA)/triphenylphosphine (TPP)/tetrapotassium hexacyanoferrate trihydrate (THT), as well as CaCO3 are explored to fabricate a core-shell-corona nanoparticle (VMMFTTC) for on-demand anti-tumor immunotherapy. After application, the tumor-specific acidic environment first decomposed CaCO3 corona, which significantly levitates the pH value of tumor tissue to convert M2 type macrophage to the antitumor M1 type. The resulting VMMFTT would then internalize in both tumor cells and macrophages via FA-assisted endocytosis and free endocytosis, respectively. These distinct processes generate different amount of VMMFTT in above two cells followed by 1) TPP-induced accumulation in the mitochondria, 2) THT-mediated effective capture of various signal ions to cut off signal transmission and further inhibit glutathione (GSH) generation, 3) ions catalyzed reactive oxygen species (ROS) production through Fenton reaction, 4) sustained release of VK2 and MA to further enhance the ROS production and GSH depletion, which caused significant apoptosis of tumor cells and additional M2-to-M1 macrophage polarization via different processes of oxidative stress. Moreover, the primary tumor apoptosis further matures surrounding immature dendritic cells and activates T cells to continuously promote the antitumor immunotherapy.
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Nanopartículas , Neoplasias , Humanos , Espécies Reativas de Oxigênio/metabolismo , Dióxido de Silício/química , Nanopartículas/química , Estresse Oxidativo , Neoplasias/terapia , Imunoterapia , Mitocôndrias/metabolismo , Íons , Linhagem Celular TumoralRESUMO
The normal operation of organelles is critical for tumor growth and metastasis. Herein, an intelligent nanoplatform (BMAEF) is fabricated to perform on-demand destruction of mitochondria and golgi apparatus, which also generates the enhanced photothermal-immunotherapy, resulting in the effective inhibition of primary and metastasis tumor. The BMAEF has a core of mesoporous silica nanoparticles loaded with brefeldin A (BM), which is connected to ethylenebis(oxyethylenenitrilo)tetraacetic acid (EGTA) and folic acid co-modified gold nanoparticles (AEF). During therapy, the BMAEF first accumulates in tumor cells via folic acid-induced targeting. Subsequently, the schiff base/ester bond cleaves in lysosome to release brefeldin A and AEF with exposed EGTA. The EGTA further captures Ca2+ to block ion transfer among mitochondria, endoplasmic reticulum, and golgi apparatus, which not only induced dysfunction of mitochondria and golgi apparatus assisted by brefeldin A to suppress both energy and material metabolism against tumor growth and metastasis, but causes AEF aggregation for tumor-specific photothermal therapy and photothermal assisted immunotherapy. Moreover, the dysfunction of these organelles also stops the production of BMI1 and heat shock protein 70 to further enhance the metastasis inhibition and photothermal therapy, which meanwhile triggers the escape of cytochrome C to cytoplasm, leading to additional apoptosis of tumor cells.
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OBJECTIVES: To evaluate its effect of an evidence-based nursing program for nasal irrigation after endoscopic sinus surgery in patients with chronic rhinosinusitis (CRS). METHODS: A total of 66 patients with CRS were randomly divided into two groups, for which the experimental group received evidence-based nasal irrigation nursing, and the control group received conventional nursing. Differences in Sino-Nasal Outcome Test-20 (SNOT-20), visual analogue scale (VAS), Lund-Mackay CT, Endoscopic Lund Kennedy Score (LKES) and overall efficacy were assessed between the two groups. RESULTS: 2, 4 and 12 weeks after the intervention, the scores of SNOT-20, VAS, Lund-Mackay CT and LKES in the two groups were significantly lower than those before the surgery (P < 0.05). Compared with the control group, the scores were significantly lower in the experimental group (P < 0.05). 12 weeks after the intervention, the overall effective rate of treatment in the experimental group was 90.62%, while the control group was 16.43%, but the difference was not statistically significant in treatment effect (P > 0.05). CONCLUSIONS: The implementation of nasal irrigation evidence-based nursing program for patients with CRS after endoscopic sinus surgery can promote postoperative nasal mucosal recovery, improve treatment efficiency, and help improve patient comfort, quality of life and other subjective feelings. TRIAL REGISTRATION: The study was registered retrospectively with reference number ChiCTR2300075484 on 06/09/2023, available at: https://www.chictr.org.cn .
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Pólipos Nasais , Rinite , Rinossinusite , Sinusite , Humanos , Qualidade de Vida , Enfermagem Baseada em Evidências , Estudos Retrospectivos , Rinite/cirurgia , Sinusite/cirurgia , Lavagem Nasal , Endoscopia , Doença Crônica , Resultado do Tratamento , Pólipos Nasais/cirurgiaRESUMO
BACKGROUND: Hepatocellular carcinoma (HCC) is associated with a high occurrence, mortality, and poor prognosis. MLX interacting protein like (MLXIPL) is an important regulator of glucolipid metabolism and is involved in tumor progression. We aimed to clarify the role of MLXIPL in HCC and its underlying mechanisms. METHODS: The level of MLXIPL was predicted using bioinformatic analysis and verified using quantitative real-time PCR (qPCR), immunohistochemical analysis, and western blot. We assessed the effects of MLXIPL on biological behaviors using the cell counting kit-8, colony formation, and Transwell assay. Glycolysis was evaluated using the Seahorse method. The interaction between MLXIPL and mechanistic target of rapamycin kinase (mTOR) was confirmed using RNA immunoprecipitation and co-immunoprecipitation. mTOR expression was detected in HCC cells using qPCR, immunofluorescence analysis, and western blot. RESULTS: The results showed that MLXIPL levels were elevated in both HCC tissues and HCC cell lines. Knockdown of MLXIPL impeded HCC cell growth, invasion, migration, and glycolysis. Moreover, MLXIPL combined with mTOR to induce phosphorylation of mTOR. Activated mTOR abrogated the effects on cellular processes induced by MLXIPL. CONCLUSION: MLXIPL promoted the malignant progression of HCC by activating phosphorylation of mTOR, suggesting an important role of the combination of MLXIPL and mTOR in HCC.
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Fatores de Transcrição de Zíper de Leucina e Hélice-Alça-Hélix Básicos , Carcinoma Hepatocelular , Neoplasias Hepáticas , Serina-Treonina Quinases TOR , Humanos , Carcinoma Hepatocelular/patologia , Linhagem Celular Tumoral , Movimento Celular/genética , Proliferação de Células/genética , Regulação Neoplásica da Expressão Gênica , Glicólise , Neoplasias Hepáticas/patologia , Processos Neoplásicos , Fosforilação , Serina-Treonina Quinases TOR/metabolismo , Fatores de Transcrição/genética , Fatores de Transcrição de Zíper de Leucina e Hélice-Alça-Hélix Básicos/metabolismoRESUMO
Scalp pruritus is a common skin problem that remains therapeutic challenge. The relationships between the dysbiosis of microbiota and skin diseases have caught attention recently. However, there are few reports about microbiota on itchy scalp. This study investigated scalp microbial characteristics of subjects with mild scalp pruritus of undetermined origin and preliminarily screened physiological factors and bacteria potentially related to pruritus. The pruritus severity of 17 qualified females was evaluated by Visual Analogue Scale (VAS). Microbiota collection was done at both itchy (n = 20) and non-itchy sites (n = 27) at occiput and crown of the same subject and Illumina sequencing was performed at the V3-V4 hypervariable regions of 16S rRNA. The corresponding sebum content, hydration, pH, trans-epidermal water loss, erythema index and porphyrin numbers were also measured by skin tester. We identified 3044 amplicon sequence variants from 821 genera. The itchy and non-itchy sites had different microbiota structures (p = 0.045, by multivariate analysis of variance), while there were large inter- and intra-individual variations. Both sites had Staphylococcus, Cutibacterium and Lawsonella as predominant genera, which were not significantly related to pruritus. The use of three genera Lactobacillus, Morganella and Pseudomonas, could well distinguish non-itchy from itchy groups, whereas different composition patterns existed inside each group. Our investigation indicated that though the bacterial community structure on itchy scalp was individual specific, there was difference between itchy and non-itchy sites. The study provides new insights into microbiota profiling on itchy scalp, which will help microbiota-targeted therapeutic experiment or products design for scalp pruritus.
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Microbiota , Couro Cabeludo , Feminino , Humanos , Microbiota/genética , Prurido , RNA Ribossômico 16S/genética , Pele/microbiologiaRESUMO
Functionalized cyclic organic carbonates and carbamates are frequently used in a number of transition metal-catalyzed decarboxylative reactions for the construction of interesting molecules. These decarboxylative transformations have attracted more and more research attention in recent years mainly due to their advantages of less waste generation and versatile reactivities. On the basis of previous reviews on this hot topic, the present review will focus on the development of transition metal-catalyzed decarboxylative transformations of functionalized cyclic carbonates and carbamates in the last two years.
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Carbamatos/química , Carbonatos/química , Metais/química , Elementos de Transição/química , Catálise , Ciclização , DescarboxilaçãoRESUMO
[This corrects the article DOI: 10.7150/jca.27939.].
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Precise and efficient therapy of malignant tumors is always a challenge. Herein, gold nanoclusters co-modified by aggregation-induced-emission (AIE) molecules, copper ion chelator (acylthiourea) and tumor-targeting agent (folic acid) were fabricated to perform AIE-guided and tumor-specific synergistic therapy with great spatio-temporal controllability for the targeted elimination and metastasis inhibition of malignant tumors. During therapy, the functional gold nanoclusters (AuNTF) would rapidly accumulate in the tumor tissue due to the enhanced permeability and retention effect as well as folic acid-mediated tumor targeting, which was followed by endocytosis by tumor cells. After that, the overexpressed copper ions in the tumor cells would trigger the aggregation of these intracellular AuNTF via a chelation process that not only generated the photothermal agent in situ to perform the tumor-specific photothermal therapy damaging the primary tumor, but also led to the copper deficiency of tumor cells to inhibit its metastasis. Moreover, the copper ions were reduced to cuprous ions along with the chelation, which further catalysed the excess H2O2 in the tumor cells to produce cytotoxic reactive oxygen species, resulting in additional chemodynamic therapy for enhanced antitumor efficiency. The aggregation of AuNTF also activated the AIE molecules to present fluorescence, which not only imaged the therapeutic area for real-time monitoring of this tumor-specific synergistic therapy, but also allowed us to perform near-infrared radiation at the correct time point and location to achieve optimal photothermal therapy. Both in vitro and in vivo results revealed the strong tumor elimination, effective metastasis inhibition and high survival rate of tumor-bearing mice after treatment using the AuNTF nanoclusters, indicating that this AIE-guided and tumor-specific synergistic strategy could offer a promising approach for tumor therapy.
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Although immunotherapy has revolutionized oncotherapy, only ≈15% of head and neck squamous cell carcinoma (HNSCC) patients benefit from the current therapies. An immunosuppressive tumor microenvironment (TME) and dysregulation of the polycomb ring finger oncogene BMI1 are potential reasons for the failure. Herein, to promote immunotherapeutic efficacy against HNSCC, an injectable nanocomposite hydrogel is developed with a polymer framework (PLGA-PEG-PLGA) that is loaded with both imiquimod encapsulated CaCO3 nanoparticles (RC) and cancer cell membrane (CCM)-coated mesoporous silica nanoparticles containing a peptide-based proteolysis-targeting chimeras (PROTAC) for BMI1 and paclitaxel (PepM@PacC). Upon injection, this nanocomposite hydrogel undergoes in situ gelation, after which it degrades in the TME over time, releasing RC and PepM@PacC nanoparticles to respectively perform immunotherapy and chemotherapy. Specifically, the RC particles selectively manipulate tumor-associated macrophages and dendritic cells to activate a T-cell immune response, while CCM-mediated homologous targeting and endocytosis delivers the PepM@PacC particles into cancer cells, where endogenous glutathione promotes disulfide bond cleavage to release the PROTAC peptide for BMI1 degradation and frees the paclitaxel from the particle pores to elicit apoptosis meanwhile enhance immunotherapy. Thus, the nanocomposite hydrogel, which is designed to exploit multiple known vulnerabilities of HNSCC, succeeds in suppressing both growth and metastasis of HNSCC.
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Neoplasias de Cabeça e Pescoço , Imunoterapia , Humanos , Carcinoma de Células Escamosas de Cabeça e Pescoço/terapia , Nanogéis , Proteólise , Neoplasias de Cabeça e Pescoço/tratamento farmacológico , Paclitaxel/farmacologia , Paclitaxel/uso terapêutico , Microambiente TumoralRESUMO
Diabetes mellitus (DM) aggravates periodontitis, resulting in accelerated periodontal bone resorption. Disordered glucose metabolism in DM causes reactive oxygen species (ROS) overproduction resulting in compromised bone healing, which makes diabetic periodontal bone regeneration a major challenge. Inspired by the natural bone healing cascade, a mesoporous silica nanoparticle (MSN)-incorporated PDLLA (poly(dl-lactide))-PEG-PDLLA (PPP) thermosensitive hydrogel with stepwise cargo release is designed to emulate the mesenchymal stem cell "recruitment-osteogenesis" cascade for diabetic periodontal bone regeneration. During therapy, SDF-1 quickly escapes from the hydrogel due to diffusion for early rat bone marrow stem cell (rBMSC) recruitment. Simultaneously, slow degradation of the hydrogel starts to gradually expose the MSNs for sustained release of metformin, which can scavenge the overproduced ROS under high glucose conditions to reverse the inhibited osteogenesis of rBMSCs by reactivating the AMPK/ß-catenin pathway, resulting in regulation of the diabetic microenvironment and facilitation of osteogenesis. In vitro experiments indicate that the hydrogel markedly restores the inhibited migration and osteogenic capacities of rBMSCs under high glucose conditions. In vivo results suggest that it can effectively recruit rBMSCs to the periodontal defect and significantly promote periodontal bone regeneration under type 2 DM. In conclusion, our work provides a novel therapeutic strategy of a bioinspired drug-delivery system emulating the natural bone healing cascade for diabetic periodontal bone regeneration.
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Multiresponsive adjuvant nanoparticles (RMmAGL) are fabricated to perform tumor-specific photothermal therapy while regulating the behavior of tumor-associated immune cells for primary tumor eradication and metastasis inhibition. Core-satellite-like RMmAGL have a core of mannose-functionalized mesoporous silica nanoparticles loaded with the TLR7 agonist imiquimod (R837@MSN-mannose) connected via hydrazone bonds to satellites of glutamine (Glu)- and lysine (Lys)-comodified gold nanoparticles (AuNPs-Glu/Lys). During therapy, the acidic environment in tumor tissue cleaves the hydrazone bonds to release AuNPs-Glu/Lys, which further accumulate in tumor cells. After internalization, photothermal agents (aggregated AuNPs-Glu/Lys) are generated in situ through the intratumoral enzyme-catalyzed reaction between Glu and Lys, resulting in tumor-specific photothermal therapy. The detachment of AuNPs-Glu/Lys also triggers the release of R837, which matured dendritic cells (DCs) via a vaccine-like mechanism along with the tumor-associated antigens generated by photothermal therapy. These matured DCs further activates surrounding T cells for immunotherapy. Moreover, the resulting free MSN-mannose serves as an artificial glycocalyx to continuously induce the polarization of tumor-associated macrophages from an immunosuppressive phenotype to an inflammatory phenotype, thus further enhancing immunotherapy. Both in vivo and in vitro experiments demonstrate significant inhibition of malignant tumors after therapy.
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Nanopartículas Metálicas , Neoplasias , Humanos , Adjuvantes Imunológicos/uso terapêutico , Linhagem Celular Tumoral , Ouro/química , Imunoterapia/métodos , Manose/química , Terapia FototérmicaRESUMO
Compact passively Q-switched and mode-locked Nd(3+):YVO(4)/Cr(4+):YAG self-Raman laser with high mode-locked repetition rate was demonstrated. The picosecond first Stokes at 1176 nm was successfully obtained. At the maximum incident pump power, the average output power was 95 mW with the mode-locked pulse repetition rate of 940 MHz. Yellow laser output of 588.2 nm was also realized by the use of LiB(3)O(5) frequency doubling crystal.
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BACKGROUND: Circular RNAs (circRNAs) exert an important regulatory effect on cancer progression. Reportedly, circRNAs can modulate gene expression by working as molecular sponges for miRNAs. Nonetheless, many functional circRNAs in hepatocellular carcinoma (HCC) remain to be identified. This study aimed to explore the role of hsa_circ_0006789 (circ_0006789) in HCC. METHODS: The expression profile of circRNAs in HCC tumor tissues was analyzed using circRNA microarray data. Circ_0006789 expression in HCC tissues and cell lines was examined by qPCR. After circ_0006789 was overexpressed or knocked down in HCC cell lines, HCC cell growth, migration and invasion were evaluated by the CCK-8 method and Transwell experiment. RIP assay, RNA pull-down assay, dual-luciferase reporter experiment and Western blotting were adopted to investigate the regulatory mechanism among circ_0006789, microRNA (miR)-1324 and SRY (sex determining region Y)-box 12 (SOX12). RESULTS: Circ_0006789 was overexpressed in HCC tissues and cell lines. Circ_0006789 overexpression accelerated the growth, migration and invasion of HCC cells, while knockdown of circ_0006789 exerted the opposite effects. miR-1324 was confirmed as a target of circ_0006789, and miR-1324 targeted SOX12 to suppress its expression. Circ_0006789 could promote SOX12 expression by sponging miR-1324. CONCLUSION: Circ_0006789 modulates the growth, migration and invasion of HCC cells by regulating miR-1324/SOX12 axis.
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Carcinoma Hepatocelular , Neoplasias Hepáticas , MicroRNAs , Humanos , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/patologia , RNA Circular/genética , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/patologia , Regulação Neoplásica da Expressão Gênica , Proliferação de Células , Linhagem Celular Tumoral , Fatores de Transcrição SOXC/genética , Fatores de Transcrição SOXC/metabolismoRESUMO
[This corrects the article DOI: 10.7150/jca.27939.].
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Tumor microenvironments (TME) play critical roles in the growth and metastasis of tumor tissue, which provide a promising way to treat malignant tumor via manipulation of TME. However, developing proper strategy to effectively control TME is still a challenge. Herein, a Ce6@AT-PEG-MSN-Pt (CAPMP) nanomotor is fabricated to spontaneously move in tumor tissue and concurrently perform the enhanced manipulation of various tumor microenvironments including copper levels, hypoxia, local temperature and reactive oxygen species (ROS) for effective tumor therapy. The CAPMP nanomotor consists of a janus platinum-mesoporous silica core with acyl thioureas groups (copper chelator) conjugated polyethylene glycol on the surface and chlorin e6 (photosensitizer) in the pores. During therapy, the acyl thioureas groups on CAPMP would capture the over-expressed copper in tumor tissue and tumor cells to cause dramatic copper-deficiency of tumor. The chlorin e6 is in charge of the ROS (1O2) generation in tumor via photodynamic process, which would be triggered by 660 nm irradiation. The platinum layer of CAPMP served as both photothermal agent and O2 producer. It rapidly raised the local temperature under 808 nm irradiation, meanwhile converted the over-expressed H2O2 in tumor tissue to O2via catalytic reaction. The O2 production not only drove the CAPMP for sustained movement to promote its efficiency of copper capture, but reversed the hypoxic environment of tumor tissue in large and deep area, which further promoted the 1O2 generation property of CAPMP. Both in vitro and in vivo experiments demonstrate that the raise of local temperature and enhanced 1O2 concentration performed significant damage of tumor tissue for primary tumor elimination, while the copper deficiency and hypoxia reversion further hindered the migration of tumor cells for metastasis inhibition, resulting in an effective strategy to treat malignant tumor.
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Nanopartículas , Fotoquimioterapia , Humanos , Fotoquimioterapia/métodos , Microambiente Tumoral , Cobre , Platina , Espécies Reativas de Oxigênio , Peróxido de Hidrogênio , Linhagem Celular Tumoral , Fármacos Fotossensibilizantes/uso terapêutico , Hipóxia/tratamento farmacológicoRESUMO
Sufficient energy generation based on effective transport of nutrient via abundant blood vessels in tumor tissue and subsequent oxidative metabolism in mitochondria is critical for growth, proliferation and migration of tumor. Thus the strategy to cut off this transport pathway (blood vessels) and simultaneously close the power house (mitochondria) is highly desired for tumor treatment. Herein, we fabricated a bionic nanocarrier with core-shell-corona structure to give selective and effective tumor therapy via stepwise destruction of existed tumor vessel, inhibition of tumor angiogenesis and dysfunction of tumor mitochondria. The core of this bionic nanocarrier consists of combretastatin A4 phosphate (CA4P) and vitamin K2 (VK2) co-loaded mesoporous silica nanoparticle (MSNs), which is in charge of the vasculature destruction and mitochondrial dysfunction after cargos release. The N-tert-butylacrylamide (TBAM) and tri-sulfated N-acetylglucosamine (TSAG) shell served as artificial affinity reagent against vascular endothelial growth factor (VEGF) for angiogenesis inhibition. As to guarantee that these actions only happened in tumor, the hyaluronic acid (HA) corona was introduced to endow the nanocarrier with tumor targeting property and stimuli-responsiveness for accurate therapy. Both in vitro and in vivo results indicated that the CA4P/VK2-MSNs-TBAM/TSAG-HA (CVMMGH for short) nanocarrier combined well-controllable manipulation of tumor vasculature and tumor mitochondria to effectivly cut off the tumorigenic energy supply, which performed significant inhibition of tumor growth, demonstrating the great candidate of our strategy for effective tumor therapy.
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Nanopartículas , Neoplasias , Biônica , Humanos , Neoplasias/tratamento farmacológico , Dióxido de Silício , Fator A de Crescimento do Endotélio VascularRESUMO
OBJECTIVE: Cholangiocarcinoma (CCA) is the second most common liver cancer, characterized by late diagnosis and fatal outcome. Although miR-192-5p has been shown to have a vital role in various cancers, its role in CCA is unknown. Here, we investigated the role of miR-192-5p in CCA cell proliferation and apoptosis, and elucidated its potential mechanism of action. METHODS: The miR-192-5p expression in CCA tissues and cell lines was detected by real-time quantitative reverse transcription-polymerase chain reaction. Cell proliferation was analyzed using the cell counting Kit-8 and 5-bromodeoxyuridine staining assays, while apoptosis was examined by flow cytometry and the terminal deoxynucleotidyl transferase deoxyuridine triphosphate nick-end labeling assay. Western blot analysis was used to measure the expression of cell proliferation and apoptosis-related proteins, as well as MEK/ERK signaling pathway-related proteins. RESULTS: MiR-192-5p was highly expressed in CCA tissues and cell lines. Overexpression of miR-192-5p significantly promoted CCA proliferation, and inhibited apoptosis. The MEK inhibitor, PD98059, reversed these miR-192-5p-induced effects on MEK/ERK signaling-associated protein expression, proliferation promotion, and apoptosis inhibition in TFK-1 cells. CONCLUSION: MiR-192-5p promotes proliferation and suppressed apoptosis of CCA cells via the MEK/ERK pathway, which may be a potential therapeutic strategy for CCA treatment.
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A decarboxylative protocol has been developed toward a range of carbocycles. The key success is based on the use of a batch of newly designed cyclic carbonates as substrates that can provide carbon-carbon zwitterion intermediate under palladium catalysis. The kinetics of the reactions are controllable toward either strained seven- or thermodynamically more favored five-membered carbocycles. The release of this chemistry will shed light on the synthesis of complex and valuable cyclic structures.
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The monomer 1 derived from achiral 1-(aminoxy)cyclopropanecarboxylic acid (OAcc) and oligopeptides 2-9 consisting of a chiral alpha-aminoxy acid and an achiral alpha-aminoxy acid such as OAcc were synthesized and their structures characterized. The eight-membered-ring intramolecular hydrogen bond, namely the alpha N-O turn, was formed between adjacent residues independent of their chirality. However, the helix formation was sequence-dependent. Dipeptide 2 bearing chiral alpha-aminoxy acid (d-OAA) at the N-terminus and achiral OAcc at the C-terminus preferentially adopted a right-handed 1.8(8) helical structure, but dipeptide 3 (OAcc-d-OAA) did not. Theoretical calculation results, in good agreement with experimental ones, revealed that the biased handedness of alpha N-O turn found in OAcc residue depends on its preceding chiral residue. It was then found that the helical conformation was destroyed in the case of oligopeptides 6 and 7 [OAA-(OAcc)(n), n = 2, 3]. The crystal structure of tripeptide 8 ((i)PrCO-d-OVal-OAcc-d-OVal-NH(i)Bu) further disclosed the helical structure formed by three consecutive homochiral alpha N-O turns. This study has uncovered achiral aminoxy acid residues such as the OAcc unit as a useful building block to be incorporated into chiral aminoxy peptides to mimic chiral helix structure.
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Aminoácidos/química , Ciclopropanos/química , Dipeptídeos/química , Nitrogênio/química , Oligopeptídeos/síntese química , Oxigênio/química , Dicroísmo Circular , Cristalografia por Raios X , Ciclopropanos/síntese química , Modelos Moleculares , Conformação Molecular , Dados de Sequência Molecular , Estrutura Molecular , Ressonância Magnética Nuclear Biomolecular , Oligopeptídeos/químicaRESUMO
The reactions of 1-sulfonyl-1H-indazoles under basic conditions are discussed, and the direct N-alkylation and Kemp elimination reactions of these compounds are reported. A series of 2-(p-tosylamino)benzonitriles and N-alkyl indazoles were prepared in good yields. Moreover, the 2-(p-tosylamino)benzonitriles could be transformed into a diverse range of important derivatives in a one-pot reaction. This method was successfully applied to the total syntheses of quindolinone and cryptolepinone; quindolinone was prepared in a one-pot reaction from 1-sulfonyl-1H-indazole.