Abstract Tumor-associated macrophages (TAMs) constitute a significant component of the tumor microenvironment. This work reviewed the latest progress in comprehending the function of TAMs and their strategies for cancer therapy. TAMs are highly heterogeneous and plastic and exhibit different functional phenotypes in response to different signal stimuli. The emergence of single-cell technologies allows us to revisit their diversity in cancer. When their pro-inflammatory function is activated, antitumor TAMs support and activate adaptive immune cells to eliminate cancer cells through T cell-mediated killing. In the context of cancer, anti-inflammatory TAMs play a variety of pro-tumor functions, such as releasing cytokines to promote the recruitment of bone marrow cells, promoting tumor angiogenesis, and inhibiting cytotoxic T cell function. The plasticity of TAMs makes them a potential tumor therapeutic target, so finally, we updated strategies for targeting TAMs and the TAM-targeting agents currently being evaluated in clinical trials.
摘要 肿瘤相关巨噬细胞（TAMs）是肿瘤微环境的重要组成部分。这项工作回顾了在理解 TAMs 功能及其癌症治疗策略方面的最新进展。TAMs具有高度异质性和可塑性，在不同信号刺激下表现出不同的功能表型。单细胞技术的出现让我们得以重新审视它们在癌症中的多样性。当它们的促炎功能被激活时，抗肿瘤 TAM 支持并激活适应性免疫细胞，通过 T 细胞介导的杀伤来消灭癌细胞。在癌症背景下，抗炎 TAMs 发挥着多种促癌功能，如释放细胞因子促进骨髓细胞募集、促进肿瘤血管生成、抑制细胞毒性 T 细胞功能等。TAMs的可塑性使其成为潜在的肿瘤治疗靶点，因此我们最后更新了靶向TAMs的策略以及目前正在临床试验中评估的TAM靶向药物。
{"title":"Roles of Tumor-Associated Macrophages in Tumor Environment and Strategies for Targeting Therapy","authors":"Meng-Qi Liu, Jia-Wei Zhang, Jianjia Zhu","doi":"10.1055/s-0043-1777704","DOIUrl":"https://doi.org/10.1055/s-0043-1777704","url":null,"abstract":"Abstract Tumor-associated macrophages (TAMs) constitute a significant component of the tumor microenvironment. This work reviewed the latest progress in comprehending the function of TAMs and their strategies for cancer therapy. TAMs are highly heterogeneous and plastic and exhibit different functional phenotypes in response to different signal stimuli. The emergence of single-cell technologies allows us to revisit their diversity in cancer. When their pro-inflammatory function is activated, antitumor TAMs support and activate adaptive immune cells to eliminate cancer cells through T cell-mediated killing. In the context of cancer, anti-inflammatory TAMs play a variety of pro-tumor functions, such as releasing cytokines to promote the recruitment of bone marrow cells, promoting tumor angiogenesis, and inhibiting cytotoxic T cell function. The plasticity of TAMs makes them a potential tumor therapeutic target, so finally, we updated strategies for targeting TAMs and the TAM-targeting agents currently being evaluated in clinical trials.","PeriodicalId":19767,"journal":{"name":"Pharmaceutical Fronts","volume":"38 1","pages":"e254 - e273"},"PeriodicalIF":0.0,"publicationDate":"2023-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139341312","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
In our previous studies, Fenazinel has shown good neuroprotective effects; however, when Fenazinel entered phase 1 clinical trials, it was associated with certain side effects. This study aimed to explore novel neuroprotective agents with higher potency and lower toxicity. Evidence suggested that cinnamic acid and its analogs may serve as promising lead compounds for stroke treatment. In this study, a series of Fenazinel derivatives were first synthesized with potential neuroprotective effects with fragments including cinnamic acid and its analogs as key functional groups. The methyl thiazolyl tetrazolium assay was performed to assess the neuroprotective effects of the compounds in glutamate-induced neurotoxicity in SH-SY5Y cells. The hERG binding assay was conducted to assess drug-induced QT prolongation or other cardiotoxicity. The neuroprotective activity of the most potent compound in vivo was tested through the survival time of mice under the hypoxic condition and a middle cerebral artery occlusion model. Our data suggested that among those derivatives, compound 9d exhibited potent neuroprotective activity in vitro comparable to Fenazinel at the test concentrations. Significantly, 9d exhibited weak hERG inhibitory activity, showing moderate activities in both hypoxia-tolerant and MCAO models in vivo. Given the above, 9d has the potential for the treatment of stroke and could be considered a lead neuroprotective agent for further development.
{"title":"Design, Synthesis, and Neuroprotective Effects of Novel Cinnamamide-Piperidine and Piperazine Derivatives","authors":"Jia-Yi Li, Xin-Yan Peng, Yi-Lei Huang, Ling Jiang, Jian-Qi Li, Xue-Zhi Yang, Qing-Wei Zhang","doi":"10.1055/s-0043-1774288","DOIUrl":"https://doi.org/10.1055/s-0043-1774288","url":null,"abstract":"In our previous studies, Fenazinel has shown good neuroprotective effects; however, when Fenazinel entered phase 1 clinical trials, it was associated with certain side effects. This study aimed to explore novel neuroprotective agents with higher potency and lower toxicity. Evidence suggested that cinnamic acid and its analogs may serve as promising lead compounds for stroke treatment. In this study, a series of Fenazinel derivatives were first synthesized with potential neuroprotective effects with fragments including cinnamic acid and its analogs as key functional groups. The methyl thiazolyl tetrazolium assay was performed to assess the neuroprotective effects of the compounds in glutamate-induced neurotoxicity in SH-SY5Y cells. The hERG binding assay was conducted to assess drug-induced QT prolongation or other cardiotoxicity. The neuroprotective activity of the most potent compound in vivo was tested through the survival time of mice under the hypoxic condition and a middle cerebral artery occlusion model. Our data suggested that among those derivatives, compound 9d exhibited potent neuroprotective activity in vitro comparable to Fenazinel at the test concentrations. Significantly, 9d exhibited weak hERG inhibitory activity, showing moderate activities in both hypoxia-tolerant and MCAO models in vivo. Given the above, 9d has the potential for the treatment of stroke and could be considered a lead neuroprotective agent for further development.","PeriodicalId":19767,"journal":{"name":"Pharmaceutical Fronts","volume":"42 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135298141","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Aisha Azad, Hajra Zafar, Faisal Raza, Muhammad Sulaiman
Abstract Methods for nanoparticle (NP) synthesis of the past were costly, generating toxic compounds, which necessitates a reduction in toxic contamination associated with chemical and physical syntheses. Green nano synthesis using plant extracts has emerged as a sustainable alternative in nanotechnology with applications in various fields. Factors such as pH, extract and salt concentrations, temperature, solvent, biomolecules in plants, and reaction time significantly influence the quality and quantity of metallic NPs synthesized via green nanotechnology. This review highlights crucial factors affecting the size and shape of metallic NPs as the overall properties of the NPs are size- and shape-dependent. Current and future research in green nano synthesis holds promise for expanding our understanding of the parameters that control the synthesis, size, and shape of NPs. Further investigation is necessary to comprehend the impact of these parameters on the synthesis of metallic NPs using plant extracts, which is considered the most sustainable approach for large-scale production.
{"title":"Factors Influencing the Green Synthesis of Metallic Nanoparticles Using Plant Extracts: A Comprehensive Review","authors":"Aisha Azad, Hajra Zafar, Faisal Raza, Muhammad Sulaiman","doi":"10.1055/s-0043-1774289","DOIUrl":"https://doi.org/10.1055/s-0043-1774289","url":null,"abstract":"Abstract Methods for nanoparticle (NP) synthesis of the past were costly, generating toxic compounds, which necessitates a reduction in toxic contamination associated with chemical and physical syntheses. Green nano synthesis using plant extracts has emerged as a sustainable alternative in nanotechnology with applications in various fields. Factors such as pH, extract and salt concentrations, temperature, solvent, biomolecules in plants, and reaction time significantly influence the quality and quantity of metallic NPs synthesized via green nanotechnology. This review highlights crucial factors affecting the size and shape of metallic NPs as the overall properties of the NPs are size- and shape-dependent. Current and future research in green nano synthesis holds promise for expanding our understanding of the parameters that control the synthesis, size, and shape of NPs. Further investigation is necessary to comprehend the impact of these parameters on the synthesis of metallic NPs using plant extracts, which is considered the most sustainable approach for large-scale production.","PeriodicalId":19767,"journal":{"name":"Pharmaceutical Fronts","volume":"43 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135297808","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Wound healing is an intricate and orderly process of events that occur in response to external trauma, resulting in tissue repair and reconstruction. This process typically involves three phases, including inflammation, angiogenesis, and extracellular matrix remodeling, and any disruption to this process may delay the healing of the wound. Chronic wounds associated with diabetes, in particular, are notorious because they are difficult to handle in a timely and orderly manner. During the treatment of the disease, drugs usually accumulate in the stratum corneum due to the skin barrier, leading to a reduction of the drug's bioavailability. Encouragingly, among the treatment strategies, microneedles (MNs) represent a novel and painless drug delivery method that promotes wound healing in diabetic patients by enabling the drug to reach the dermal layer efficiently. In this review, recent advances of MNs in the treatment of diabetic wound healing are summarized by categorizing the designs and strategies. We finally provide an outlook on the prospects and challenges of MN-based therapies for diabetic wound healing in the future.
{"title":"Advances of Microneedle Patch in Diabetic Wound Healing","authors":"Yong-Nian Zeng, Yin-Li Jin, Wei Li","doi":"10.1055/s-0043-1777440","DOIUrl":"https://doi.org/10.1055/s-0043-1777440","url":null,"abstract":"Wound healing is an intricate and orderly process of events that occur in response to external trauma, resulting in tissue repair and reconstruction. This process typically involves three phases, including inflammation, angiogenesis, and extracellular matrix remodeling, and any disruption to this process may delay the healing of the wound. Chronic wounds associated with diabetes, in particular, are notorious because they are difficult to handle in a timely and orderly manner. During the treatment of the disease, drugs usually accumulate in the stratum corneum due to the skin barrier, leading to a reduction of the drug's bioavailability. Encouragingly, among the treatment strategies, microneedles (MNs) represent a novel and painless drug delivery method that promotes wound healing in diabetic patients by enabling the drug to reach the dermal layer efficiently. In this review, recent advances of MNs in the treatment of diabetic wound healing are summarized by categorizing the designs and strategies. We finally provide an outlook on the prospects and challenges of MN-based therapies for diabetic wound healing in the future.","PeriodicalId":19767,"journal":{"name":"Pharmaceutical Fronts","volume":"31 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-08-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139352029","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Continuous flow chemistry is an enabling technology for automated synthesis. Artificial intelligence (AI) is a powerful tool in various areas of automated synthesis in flow chemistry, including process analysis technology and synthesis reaction optimization. The merger of continuous flow chemistry and AI drives chemical production in a more intelligent, automated, and flexible direction. This review discusses the recent application of AI in analyzing and optimizing chemical products produced by continuous flow chemistry with the most innovative equipment and techniques.
{"title":"A Review of the Applications of Artificial Intelligence in the Process Analysis and Optimization of Chemical Products","authors":"Runqiu Shen, Weike Su","doi":"10.1055/s-0043-1777425","DOIUrl":"https://doi.org/10.1055/s-0043-1777425","url":null,"abstract":"Continuous flow chemistry is an enabling technology for automated synthesis. Artificial intelligence (AI) is a powerful tool in various areas of automated synthesis in flow chemistry, including process analysis technology and synthesis reaction optimization. The merger of continuous flow chemistry and AI drives chemical production in a more intelligent, automated, and flexible direction. This review discusses the recent application of AI in analyzing and optimizing chemical products produced by continuous flow chemistry with the most innovative equipment and techniques.","PeriodicalId":19767,"journal":{"name":"Pharmaceutical Fronts","volume":"86 1","pages":"e219 - e226"},"PeriodicalIF":0.0,"publicationDate":"2023-07-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139353467","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Abstract Peroxides, as high-efficiency oxidants, are widely used in various areas of industry, such as chemical, pharmaceutical, environmental protection, etc. However, their applications in batches are limited due to their explosive and unstable nature. Continuous flow reactions have the advantages of a large area-to-surface ratio, high mixing efficiency, high mass and heat transfer performance, accurate control of process parameters, and high security. These are beneficial for the improvement of the product yield and the reduction of the reaction time and risk. Thus, in the reaction involving peroxide, continuous flow technology can effectively improve the operational safety and enhance the reaction efficiency of peroxides. This review summarized the applications of peroxides in various organic syntheses in continuous-flow chemistry. These examples illustrated the promising prospects of peroxides in green organic synthesis.
{"title":"The Application of Peroxide for Organic Synthesis in Continuous Flow Chemistry","authors":"Rui Zhu, Yi-Bo Zhou, Han-Qi Zhou, Feng-Fan Liu","doi":"10.1055/s-0043-1777426","DOIUrl":"https://doi.org/10.1055/s-0043-1777426","url":null,"abstract":"Abstract Peroxides, as high-efficiency oxidants, are widely used in various areas of industry, such as chemical, pharmaceutical, environmental protection, etc. However, their applications in batches are limited due to their explosive and unstable nature. Continuous flow reactions have the advantages of a large area-to-surface ratio, high mixing efficiency, high mass and heat transfer performance, accurate control of process parameters, and high security. These are beneficial for the improvement of the product yield and the reduction of the reaction time and risk. Thus, in the reaction involving peroxide, continuous flow technology can effectively improve the operational safety and enhance the reaction efficiency of peroxides. This review summarized the applications of peroxides in various organic syntheses in continuous-flow chemistry. These examples illustrated the promising prospects of peroxides in green organic synthesis.","PeriodicalId":19767,"journal":{"name":"Pharmaceutical Fronts","volume":"33 1","pages":"e243 - e253"},"PeriodicalIF":0.0,"publicationDate":"2023-07-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139353801","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Yi-Bo Zhou, Rui Zhu, Han-Qi Zhou, Jun-Hua Li, Feng-Fan Liu
Abstract Tetrabutylurea (TBU) is mainly used as a working liquid in the preparation of hydrogen peroxide via the anthraquinone process. It is reported that dibutylamine ( A ) reacts with dibutylcarbamyl chloride ( B ) to produce TBU in the presence of triphosgene, which is the decisive step of the reaction. In this study, we aimed to investigate the reaction kinetics of the decisive step to gain more insight into the reaction. The reaction order as well as the pre-exponential factors ( A ) and the activation energies ( E a ) were determined. The kinetic study suggested that the total order of the reaction is second. E a = 5.4 × 10 4 J/mol, A = 1.5257 × 10 7 L/(mol × min), calculated through a second-order kinetics model. The accuracy and applicability of the kinetic model were verified by serval experiments, showing that enhancing reaction temperature could shorten the reaction time and increase the conversion rate.
摘要 四丁基脲（TBU）主要用作蒽醌法制备过氧化氢的工作液。据报道，二正丁胺（A）与二正丁基氨基甲酰氯（B）在三光气存在下反应生成 TBU，这是反应的决定性步骤。在本研究中，我们旨在研究决定性步骤的反应动力学，以深入了解该反应。我们测定了反应顺序、前指数（A）和活化能（E a）。动力学研究表明，反应的总顺序为第二顺序。通过二阶动力学模型计算得出 E a = 5.4 × 10 4 J/mol，A = 1.5257 × 10 7 L/（mol × min）。伺服实验验证了该动力学模型的准确性和适用性，表明提高反应温度可缩短反应时间并提高转化率。
{"title":"Kinetic Study of the Acylation Reaction of Dibutylcarbamyl Chloride and Dibutylamine","authors":"Yi-Bo Zhou, Rui Zhu, Han-Qi Zhou, Jun-Hua Li, Feng-Fan Liu","doi":"10.1055/s-0043-1777286","DOIUrl":"https://doi.org/10.1055/s-0043-1777286","url":null,"abstract":"Abstract Tetrabutylurea (TBU) is mainly used as a working liquid in the preparation of hydrogen peroxide via the anthraquinone process. It is reported that dibutylamine ( A ) reacts with dibutylcarbamyl chloride ( B ) to produce TBU in the presence of triphosgene, which is the decisive step of the reaction. In this study, we aimed to investigate the reaction kinetics of the decisive step to gain more insight into the reaction. The reaction order as well as the pre-exponential factors ( A ) and the activation energies ( E a ) were determined. The kinetic study suggested that the total order of the reaction is second. E a = 5.4 × 10 4 J/mol, A = 1.5257 × 10 7 L/(mol × min), calculated through a second-order kinetics model. The accuracy and applicability of the kinetic model were verified by serval experiments, showing that enhancing reaction temperature could shorten the reaction time and increase the conversion rate.","PeriodicalId":19767,"journal":{"name":"Pharmaceutical Fronts","volume":"19 1","pages":"e282 - e287"},"PeriodicalIF":0.0,"publicationDate":"2023-07-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139353832","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
The Pictet–Spengler reaction is one of the important methodological arsenals in synthetic and medicinal chemistry, acting as an amenable tool for preparing tetrahydroisoquinoline, tetrahydro-β-carbolines, polycyclic skeletons, and value-added products. More than 100 years after its initial discovery, the Pictet–Spengler reaction's response has not withdrawn from the stage, but it has once again become the focus of attention with new features. The review summarizes recent advances in Pictet–Spengler-based multicomponent reactions from 2007 to 2022, including three-component and four-component Pictet–Spengler cyclization reactions in the presence of metal catalysts, organocatalysts, biological enzyme catalysts, and so on. These Pictet–Spengler-based multicomponent protocols provide an atom-/step economic approach for the synthesis of a library of new chemical entities.
{"title":"Pictet–Spengler-Based Multicomponent Domino Reactions to Construct Polyheterocycles","authors":"Jun-Duo Hu, Li-Liang Huang, Huang-Di Feng","doi":"10.1055/s-0043-1777345","DOIUrl":"https://doi.org/10.1055/s-0043-1777345","url":null,"abstract":"The Pictet–Spengler reaction is one of the important methodological arsenals in synthetic and medicinal chemistry, acting as an amenable tool for preparing tetrahydroisoquinoline, tetrahydro-β-carbolines, polycyclic skeletons, and value-added products. More than 100 years after its initial discovery, the Pictet–Spengler reaction's response has not withdrawn from the stage, but it has once again become the focus of attention with new features. The review summarizes recent advances in Pictet–Spengler-based multicomponent reactions from 2007 to 2022, including three-component and four-component Pictet–Spengler cyclization reactions in the presence of metal catalysts, organocatalysts, biological enzyme catalysts, and so on. These Pictet–Spengler-based multicomponent protocols provide an atom-/step economic approach for the synthesis of a library of new chemical entities.","PeriodicalId":19767,"journal":{"name":"Pharmaceutical Fronts","volume":"160 1","pages":"e227 - e242"},"PeriodicalIF":0.0,"publicationDate":"2023-07-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139355649","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
p-Aminophenol (AP) is the key intermediate of the traditional synthesis of paracetamol. The method of obtaining AP included a selective reduction reaction of the generation of N-arylhydroxylamine (AHA) using nitrobenzene (NB) as the raw material, followed by a Bamberger rearrangement reaction to transfer AHA to the target product. The generation of AHA is a key step, but due to its structural instability and the incompatibility of the two reaction systems, one-pot synthesis of paracetamol faces great challenges. Considering that using flow reactors in series may avoid the problems faced by batch reactors, the article presents the strategy to obtain paracetamol via a continuous flow technology. In particular, we focus on condition screening in total synthesis experiments, including hydrogenation, Bamberger rearrangement, and amidation in flow. The continuous three-step synthesis process used NB as a raw material to generate AHA, which entered the downstream for timely conversion, achieving in situ on-demand preparation of the unstable intermediate AHA, avoiding cumbersome processing and storage processes. Moreover, each step of the reaction system exhibits excellent compatibility, and the work-up is simple.
{"title":"Multistep Synthesis of Paracetamol in Continuous Flow","authors":"Jian-li Chen, Jing-Yu Hu, Qi-Fan Wang, Peng Ge, Quan-Hui Wang, Zi-Shuo Lou","doi":"10.1055/s-0043-1772252","DOIUrl":"https://doi.org/10.1055/s-0043-1772252","url":null,"abstract":"\u0000 p-Aminophenol (AP) is the key intermediate of the traditional synthesis of paracetamol. The method of obtaining AP included a selective reduction reaction of the generation of N-arylhydroxylamine (AHA) using nitrobenzene (NB) as the raw material, followed by a Bamberger rearrangement reaction to transfer AHA to the target product. The generation of AHA is a key step, but due to its structural instability and the incompatibility of the two reaction systems, one-pot synthesis of paracetamol faces great challenges. Considering that using flow reactors in series may avoid the problems faced by batch reactors, the article presents the strategy to obtain paracetamol via a continuous flow technology. In particular, we focus on condition screening in total synthesis experiments, including hydrogenation, Bamberger rearrangement, and amidation in flow. The continuous three-step synthesis process used NB as a raw material to generate AHA, which entered the downstream for timely conversion, achieving in situ on-demand preparation of the unstable intermediate AHA, avoiding cumbersome processing and storage processes. Moreover, each step of the reaction system exhibits excellent compatibility, and the work-up is simple.","PeriodicalId":19767,"journal":{"name":"Pharmaceutical Fronts","volume":"31 1","pages":"e161 - e167"},"PeriodicalIF":0.0,"publicationDate":"2023-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"81305191","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
As a safe and efficient synthesis technique, flow chemistry has recently gained attention in the pharmaceutical, materials, and environmental protection industries. However, researchers always face challenges in handling samples and selecting sufficiently flexible analytical techniques. Generally, real-time process analysis is crucial for monitoring reactions. The combination of flow chemistry with real-time process analysis can be beneficial for studying reaction kinetics and thermodynamics, monitoring, and control of the chemical synthesis processes, reaction optimization of macro and microreactors, and qualitative and quantitative analyses of compounds. Thus far, studies investigating the combination of flow chemistry with inline monitoring have included ultraviolet–infrared spectroscopy, Raman spectroscopy, gas chromatography, mass spectrometry, liquid chromatography, nuclear magnetic resonance (NMR) spectroscopy, and other automated conventional or unconventional methods. This review sheds light on applying inline infrared and inline NMR spectroscopies in flow chemistry.
{"title":"A Review of Inline Infrared and Nuclear Magnetic Resonance Applications in Flow Chemistry","authors":"Yan Zhang, Wei Su","doi":"10.1055/s-0043-1776906","DOIUrl":"https://doi.org/10.1055/s-0043-1776906","url":null,"abstract":"As a safe and efficient synthesis technique, flow chemistry has recently gained attention in the pharmaceutical, materials, and environmental protection industries. However, researchers always face challenges in handling samples and selecting sufficiently flexible analytical techniques. Generally, real-time process analysis is crucial for monitoring reactions. The combination of flow chemistry with real-time process analysis can be beneficial for studying reaction kinetics and thermodynamics, monitoring, and control of the chemical synthesis processes, reaction optimization of macro and microreactors, and qualitative and quantitative analyses of compounds. Thus far, studies investigating the combination of flow chemistry with inline monitoring have included ultraviolet–infrared spectroscopy, Raman spectroscopy, gas chromatography, mass spectrometry, liquid chromatography, nuclear magnetic resonance (NMR) spectroscopy, and other automated conventional or unconventional methods. This review sheds light on applying inline infrared and inline NMR spectroscopies in flow chemistry.","PeriodicalId":19767,"journal":{"name":"Pharmaceutical Fronts","volume":"5 1","pages":"e209 - e218"},"PeriodicalIF":0.0,"publicationDate":"2023-07-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139362434","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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