Pub Date : 2023-09-01DOI: 10.1177/17475198231202967
Yingcong Yu, Yan Zhao, Yajing Wang, Xianfeng Huang
PDE4 inhibitors exhibit anti-stress and antidepressant-like abilities by catalyzing the hydrolysis of cAMP, a primary regulator for intracellular communication in the brain. Herein, novel diarylpyrazole derivatives are synthesized and investigated for their ability to inhibit PDE4. In vitro studies indicate that most of the synthesized compounds show significant potency for the inhibition of PDE4. Specifically, N-(4-(3-(3,5-dimethoxyphenyl)-1 H-pyrazol-5-yl)benzyl)-2-morpholinoethan-1-amine exhibits the most potent PDE4 inhibition, with an IC 50 value of ca. 0.09 μM. It also produces antidepressant-like activities in sugar water consumption and in forced swimming tests in vivo.
PDE4抑制剂通过催化cAMP水解表现出抗应激和抗抑郁样能力，cAMP是大脑细胞内通讯的主要调节因子。本文合成了新的二芳基吡唑衍生物，并研究了它们抑制PDE4的能力。体外研究表明，大多数合成的化合物对PDE4具有显著的抑制作用。具体来说，N-(4-(3-(3,5-二甲氧基苯基)-1 h -吡唑-5-基)苄基)-2- morpholinoee1 -胺具有最有效的PDE4抑制作用，其ic50值约为0.09 μM。它还在糖水消耗和体内强迫游泳试验中产生类似抗抑郁的活动。
{"title":"Design and synthesis of novel PDE4 inhibitors as potential candidates for antidepressant agents","authors":"Yingcong Yu, Yan Zhao, Yajing Wang, Xianfeng Huang","doi":"10.1177/17475198231202967","DOIUrl":"https://doi.org/10.1177/17475198231202967","url":null,"abstract":"PDE4 inhibitors exhibit anti-stress and antidepressant-like abilities by catalyzing the hydrolysis of cAMP, a primary regulator for intracellular communication in the brain. Herein, novel diarylpyrazole derivatives are synthesized and investigated for their ability to inhibit PDE4. In vitro studies indicate that most of the synthesized compounds show significant potency for the inhibition of PDE4. Specifically, N-(4-(3-(3,5-dimethoxyphenyl)-1 H-pyrazol-5-yl)benzyl)-2-morpholinoethan-1-amine exhibits the most potent PDE4 inhibition, with an IC 50 value of ca. 0.09 μM. It also produces antidepressant-like activities in sugar water consumption and in forced swimming tests in vivo.","PeriodicalId":15323,"journal":{"name":"Journal of Chemical Research","volume":"2013 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":"135690326","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Large accumulations of copper (Cu) ions in the human body may cause damage, including organ and brain damage. In recent years, studies have proven that a large accumulation of Cu ions can lead to Parkinson’s disease and Alzheimer’s disease; therefore, it is great important to develop novel strategies for detecting trace Cu in environmental and biological samples. In this work, we designed two new coumarin-based colorimetric and fluorescent probes, HQ1 and HQ2. These two probes could selectively respond to Cu 2+ with obvious color and fluorescence changes, and the presence of other metal ions had no effect on these changes. The two probes also exhibited high sensitivity for Cu 2+ , with a detection limit as low as 1.81 × 10 –8 M/1.57 × 10 –8 M. Notably, the two probes showed potential practical applications and were successfully used for detecting Cu 2+ in a test strip, A549 cells, and living zebrafish larvae.
{"title":"Two novel coumarin-based fluorescent probes for the detection of Cu<sup>2+</sup> and biological applications","authors":"Canxin Zhang, Li Huang, Lizhen Wang, Xia Meng, Jianhua Zhou, Hongdong Duan","doi":"10.1177/17475198231199438","DOIUrl":"https://doi.org/10.1177/17475198231199438","url":null,"abstract":"Large accumulations of copper (Cu) ions in the human body may cause damage, including organ and brain damage. In recent years, studies have proven that a large accumulation of Cu ions can lead to Parkinson’s disease and Alzheimer’s disease; therefore, it is great important to develop novel strategies for detecting trace Cu in environmental and biological samples. In this work, we designed two new coumarin-based colorimetric and fluorescent probes, HQ1 and HQ2. These two probes could selectively respond to Cu 2+ with obvious color and fluorescence changes, and the presence of other metal ions had no effect on these changes. The two probes also exhibited high sensitivity for Cu 2+ , with a detection limit as low as 1.81 × 10 –8 M/1.57 × 10 –8 M. Notably, the two probes showed potential practical applications and were successfully used for detecting Cu 2+ in a test strip, A549 cells, and living zebrafish larvae.","PeriodicalId":15323,"journal":{"name":"Journal of Chemical Research","volume":"28 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":"135638198","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-09-01DOI: 10.1177/17475198231195806
Jian-Qiao Lang, Hong-Ze Gang, Bo-Zhong Mu, Shi-Zhong Yang
Various isomers can be observed in the Friedel–Crafts alkylation of benzene. However, the mechanism and influence of these isomerization reactions were still unclear. In this work, several methyl phenylundecanoate were analyzed by gas chromatography–mass spectrometry to explore the isomerization of the Friedel–Crafts alkylation. The results showed that there were three isomerization reactions in the Friedel–Crafts alkylation reaction: five isomers of methyl 6–10-phenylundecanoate due to carbocation rearrangement, five isomers of methyl 6–9-methyldecanoate and methyl undecanoate due to methyl migration, and the loss of neutral alcohol molecular fragments due to hydrogen transfer. At higher reaction temperature, carbocation migration was more active and the formation of methyl undecanoate isomers was observed. There was a competitive relationship between the production of methyl undecanoate isomers and methyl phenylundecanoate isomers. In addition, the hydrogen transfer could be initiated in the presence of unsaturated bonds and alcohol molecules lost as a fragment. The hydrogen from the phenyl groups, which were at a different position on the carbon chain of fatty acid esters, could be transferred to the ester group. It was found that hydrogen could be transferred intramolecularly over a long range. This work revealed the isomerization process in the Friedel–Crafts alkylation and further deepened the understanding of alkylation.
{"title":"Carbocation rearrangement, methyl migration, and long-range hydrogen transfer in phenyl fatty acid esters","authors":"Jian-Qiao Lang, Hong-Ze Gang, Bo-Zhong Mu, Shi-Zhong Yang","doi":"10.1177/17475198231195806","DOIUrl":"https://doi.org/10.1177/17475198231195806","url":null,"abstract":"Various isomers can be observed in the Friedel–Crafts alkylation of benzene. However, the mechanism and influence of these isomerization reactions were still unclear. In this work, several methyl phenylundecanoate were analyzed by gas chromatography–mass spectrometry to explore the isomerization of the Friedel–Crafts alkylation. The results showed that there were three isomerization reactions in the Friedel–Crafts alkylation reaction: five isomers of methyl 6–10-phenylundecanoate due to carbocation rearrangement, five isomers of methyl 6–9-methyldecanoate and methyl undecanoate due to methyl migration, and the loss of neutral alcohol molecular fragments due to hydrogen transfer. At higher reaction temperature, carbocation migration was more active and the formation of methyl undecanoate isomers was observed. There was a competitive relationship between the production of methyl undecanoate isomers and methyl phenylundecanoate isomers. In addition, the hydrogen transfer could be initiated in the presence of unsaturated bonds and alcohol molecules lost as a fragment. The hydrogen from the phenyl groups, which were at a different position on the carbon chain of fatty acid esters, could be transferred to the ester group. It was found that hydrogen could be transferred intramolecularly over a long range. This work revealed the isomerization process in the Friedel–Crafts alkylation and further deepened the understanding of alkylation.","PeriodicalId":15323,"journal":{"name":"Journal of Chemical Research","volume":"78 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":"135388226","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-09-01DOI: 10.1177/17475198231195811
Khalid A.M. Attia, Ahmed El-Olemy, Ahmed Emad F. Abbas, Sherif M. Eid
Drug impurities are now seen as a major threat to drug safety around the world, especially when it comes to carcinogenic impurities. Here, we present the first spectrophotometric approach for the quantification of lignocaine and fluorescein in the presence of 2,6-xylidine, lignocaine’s carcinogenic impurity. The approach depends on overcoming unresolved bands through a data processing strategy employing 10 affordable, simple, and sensitive spectrophotometric methods. Fluorescein analysis (1–16 μg mL −1 ) was performed using direct ultraviolet spectrophotometry (D 0 ) at 478 nm; then, the ratio subtraction method allowed the removal of interference caused by the fluorescein spectrum. From the resulting ratio spectra, 2,6-xylidine (40–160 μg mL −1 ) can be efficiently determined at 280 nm. However, lignocaine (72–320 μg mL −1 ) was analyzed using different ultraviolet-based methods, including continuous wavelet transform, ratio derivative by Savitzky–Golay filters, mean centering, second derivative of ratio spectra, ratio spectra difference spectrophotometry, extended ratio subtraction, absorbance subtraction, Q-absorbance ratio, and area under the curve. In line with International Council for Harmonization of Technical Requirements for Pharmaceuticals for Human Use (ICH), the presented approach was evaluated by its coefficients of determination, detection limits, quantification limits, and relative standard deviations. Similarly, the developed approach was assessed for whiteness, greenness, and sustainability using five assessment tools, including National Environmental Method Index, Eco-Scale Assessment, Complementary Green Analytical Procedure Index, Analytical Greenness Metric, and RGB12, offering promising results. Owing to the satisfactory analytical performance, besides the sustainability, affordability, simplicity, and cost efficiency of the presented methods, their application for quality control and in situ analysis in minimal-infrastructure laboratories increases, increasing the surveillance potential.
{"title":"A sustainable data processing approach using ultraviolet-spectroscopy as a powerful spectral resolution tool for simultaneously estimating newly approved eye solution in the presence of extremely carcinogenic impurity aided with various greenness and whiteness assessment perspectives: Application to aqueous humor","authors":"Khalid A.M. Attia, Ahmed El-Olemy, Ahmed Emad F. Abbas, Sherif M. Eid","doi":"10.1177/17475198231195811","DOIUrl":"https://doi.org/10.1177/17475198231195811","url":null,"abstract":"Drug impurities are now seen as a major threat to drug safety around the world, especially when it comes to carcinogenic impurities. Here, we present the first spectrophotometric approach for the quantification of lignocaine and fluorescein in the presence of 2,6-xylidine, lignocaine’s carcinogenic impurity. The approach depends on overcoming unresolved bands through a data processing strategy employing 10 affordable, simple, and sensitive spectrophotometric methods. Fluorescein analysis (1–16 μg mL −1 ) was performed using direct ultraviolet spectrophotometry (D 0 ) at 478 nm; then, the ratio subtraction method allowed the removal of interference caused by the fluorescein spectrum. From the resulting ratio spectra, 2,6-xylidine (40–160 μg mL −1 ) can be efficiently determined at 280 nm. However, lignocaine (72–320 μg mL −1 ) was analyzed using different ultraviolet-based methods, including continuous wavelet transform, ratio derivative by Savitzky–Golay filters, mean centering, second derivative of ratio spectra, ratio spectra difference spectrophotometry, extended ratio subtraction, absorbance subtraction, Q-absorbance ratio, and area under the curve. In line with International Council for Harmonization of Technical Requirements for Pharmaceuticals for Human Use (ICH), the presented approach was evaluated by its coefficients of determination, detection limits, quantification limits, and relative standard deviations. Similarly, the developed approach was assessed for whiteness, greenness, and sustainability using five assessment tools, including National Environmental Method Index, Eco-Scale Assessment, Complementary Green Analytical Procedure Index, Analytical Greenness Metric, and RGB12, offering promising results. Owing to the satisfactory analytical performance, besides the sustainability, affordability, simplicity, and cost efficiency of the presented methods, their application for quality control and in situ analysis in minimal-infrastructure laboratories increases, increasing the surveillance potential.","PeriodicalId":15323,"journal":{"name":"Journal of Chemical Research","volume":"21 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":"135298098","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-09-01DOI: 10.1177/17475198231184801
Thi Cam Quyen Ngo, Van Tan Lam, Hoang Thanh Tu Nguyen, Ngoc Bich Hoang, Thi Tuu Tran, My Hanh Le, Thi Nhu Dung Nguyen, Long Giang Bach
In this study, we used a synthetic aerogel based on PVA/agar/maltodextrin to remove the antibiotic ciprofloxacin (CFX) from aqueous media. Response surface method (RSM) is used to study the relationship between the factors affecting the adsorption process, thereby optimizing the adsorption efficiency, and making decisions on improving the adsorption process better sub. The research results obtained are as follows: pH2, initial CFX concentration 51 mg L −1 , adsorbent dosage 0.16 g L −1 , adsorption time 120 min, and temperature 51.5 °C reached the maximum adsorption capacity. The maximum additive is 38.63 mg g −1 . The experimental data agree with the pseudo-quadratic kinetic model and the Langmuir and Temkin isotherm models. The composite aerogel adsorbent (AE) in this study is a potential candidate for adsorbent to remove antibiotic contamination in aqueous media.
本研究采用PVA/琼脂/麦芽糊精合成气凝胶去除水中的抗生素环丙沙星(CFX)。采用响应面法(RSM)研究影响吸附过程的因素之间的关系，从而优化吸附效率，更好地改进吸附过程。研究结果如下:pH2, CFX初始浓度51 mg L−1，吸附剂用量0.16 g L−1，吸附时间120 min，温度51.5℃达到最大吸附量。最大添加量为38.63 mg g−1。实验数据符合拟二次动力学模型和Langmuir、Temkin等温线模型。本研究的复合气凝胶吸附剂(AE)是去除水中抗生素污染的潜在吸附剂。
{"title":"Optimization of the removal of the antibiotic ciprofloxacin by composite aerogels based on PVA/agar/maltodextrin","authors":"Thi Cam Quyen Ngo, Van Tan Lam, Hoang Thanh Tu Nguyen, Ngoc Bich Hoang, Thi Tuu Tran, My Hanh Le, Thi Nhu Dung Nguyen, Long Giang Bach","doi":"10.1177/17475198231184801","DOIUrl":"https://doi.org/10.1177/17475198231184801","url":null,"abstract":"In this study, we used a synthetic aerogel based on PVA/agar/maltodextrin to remove the antibiotic ciprofloxacin (CFX) from aqueous media. Response surface method (RSM) is used to study the relationship between the factors affecting the adsorption process, thereby optimizing the adsorption efficiency, and making decisions on improving the adsorption process better sub. The research results obtained are as follows: pH2, initial CFX concentration 51 mg L −1 , adsorbent dosage 0.16 g L −1 , adsorption time 120 min, and temperature 51.5 °C reached the maximum adsorption capacity. The maximum additive is 38.63 mg g −1 . The experimental data agree with the pseudo-quadratic kinetic model and the Langmuir and Temkin isotherm models. The composite aerogel adsorbent (AE) in this study is a potential candidate for adsorbent to remove antibiotic contamination in aqueous media.","PeriodicalId":15323,"journal":{"name":"Journal of Chemical Research","volume":"127 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":"135304839","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-09-01DOI: 10.1177/17475198231181624
Huong Dieu Tran, Bich Ngoc Hoang, Lam Van Tan, Thi Nhu Dung Nguyen, Tran Thi Tuu, Phung Chi Sy, Long Giang Bach
Polyvinyl alcohol/agar/maltodextrin composite membranes at different ratios are investigated for the removal of the antibiotic ciprofloxacin from water. The factors affecting the adsorption capacity of the as-synthesized membranes include time, pH, temperature, concentration, and dosage of film. The PAM244 and PAM433 membranes are subjected to optimization using response surface methodology model employing the Box–Behnken experimental design model. The optimal model has shown compatibility between the experimental value and the predicted value of the model. The correlation coefficients of PAM244 and PAM433 are recorded as R 2 = 0.999 and R 2 = 0.991, respectively. The model also proposes the optimal parameters. For PAM244, the adsorption capacity predicted from the model is 11.52 mg g –1 (42% of efficiency) at pH 5.89, a concentration of 41.28 mg L –1 , over a time period of 19.87 min, and dosage of film 2.08 g L –1 . For PAM433, the adsorption capacity predicted from the model is 10.46 mg g –1 (40% of efficiency) at pH 6.07, a concentration of 41.24 mg L –1 , over a time period of 19.59 min, and dosage of film 2.16 g L –1 . To enhance the potential of the material, the membrane reusability is also examined with the number of reuses being three times with the PAM244 membrane and twice with the PAM433 membrane.
研究了聚乙烯醇/琼脂/麦芽糊精复合膜在不同配比下对水中抗生素环丙沙星的去除效果。影响合成膜吸附能力的因素包括时间、pH、温度、浓度和膜用量。采用Box-Behnken实验设计模型，采用响应面法对PAM244和PAM433膜进行了优化。最优模型的实验值与模型预测值基本吻合。PAM244和PAM433的相关系数分别为r2 = 0.999和r2 = 0.991。该模型还提出了最优参数。在pH为5.89、浓度为41.28 mg L -1、时间为19.87 min、膜用量为2.08 g L -1的条件下，模型预测PAM244的吸附量为11.52 mg g -1(效率为42%)。在pH为6.07、浓度为41.24 mg L -1、时间为19.59 min、膜用量为2.16 g L -1的条件下，模型预测PAM433的吸附量为10.46 mg g -1(效率为40%)。为了提高材料的潜力，还研究了膜的可重复使用性，PAM244膜的重复使用次数为三次，PAM433膜的重复使用次数为两次。
{"title":"Removal of the antibiotic ciprofloxacin by using a polyvinyl alcohol/agar/maltodextrin composite membrane: Optimization by response surface methodology","authors":"Huong Dieu Tran, Bich Ngoc Hoang, Lam Van Tan, Thi Nhu Dung Nguyen, Tran Thi Tuu, Phung Chi Sy, Long Giang Bach","doi":"10.1177/17475198231181624","DOIUrl":"https://doi.org/10.1177/17475198231181624","url":null,"abstract":"Polyvinyl alcohol/agar/maltodextrin composite membranes at different ratios are investigated for the removal of the antibiotic ciprofloxacin from water. The factors affecting the adsorption capacity of the as-synthesized membranes include time, pH, temperature, concentration, and dosage of film. The PAM244 and PAM433 membranes are subjected to optimization using response surface methodology model employing the Box–Behnken experimental design model. The optimal model has shown compatibility between the experimental value and the predicted value of the model. The correlation coefficients of PAM244 and PAM433 are recorded as R 2 = 0.999 and R 2 = 0.991, respectively. The model also proposes the optimal parameters. For PAM244, the adsorption capacity predicted from the model is 11.52 mg g –1 (42% of efficiency) at pH 5.89, a concentration of 41.28 mg L –1 , over a time period of 19.87 min, and dosage of film 2.08 g L –1 . For PAM433, the adsorption capacity predicted from the model is 10.46 mg g –1 (40% of efficiency) at pH 6.07, a concentration of 41.24 mg L –1 , over a time period of 19.59 min, and dosage of film 2.16 g L –1 . To enhance the potential of the material, the membrane reusability is also examined with the number of reuses being three times with the PAM244 membrane and twice with the PAM433 membrane.","PeriodicalId":15323,"journal":{"name":"Journal of Chemical Research","volume":"103 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":"135427670","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-09-01DOI: 10.1177/17475198231196759
M John Plater, Andrea Raab, Horst Hartmann
Two 19th-century historical violet dyes from the Historische Farbstoffsammlung, Technical University of Dresden, have been analysed by liquid chromatography–mass spectrometry (LC-MS). The data are presented as charts with retention time and two scales: electron spray mass spectrometry counts ( m/z) and milli-absorption units (UV). These dyes are complex mixtures as anticipated from the synthetic methods involving partial alkylation of rosaniline or synthesis using mixtures of N-methylaniline and N,N-dimethylaniline. The charts typically show chromophores separated by CH 2 units which have separated well. Hofmann’s violet is presumably made by Hofmann’s method of synthesis, but the analyses do not verify with certainty who the inventors are because of the complexity of the dye mixtures.
{"title":"Violet dyes of the 1860s: Hofmann, Britannia, violet de Paris, Wanklyn’s, and Crystal violet (1883)","authors":"M John Plater, Andrea Raab, Horst Hartmann","doi":"10.1177/17475198231196759","DOIUrl":"https://doi.org/10.1177/17475198231196759","url":null,"abstract":"Two 19th-century historical violet dyes from the Historische Farbstoffsammlung, Technical University of Dresden, have been analysed by liquid chromatography–mass spectrometry (LC-MS). The data are presented as charts with retention time and two scales: electron spray mass spectrometry counts ( m/z) and milli-absorption units (UV). These dyes are complex mixtures as anticipated from the synthetic methods involving partial alkylation of rosaniline or synthesis using mixtures of N-methylaniline and N,N-dimethylaniline. The charts typically show chromophores separated by CH 2 units which have separated well. Hofmann’s violet is presumably made by Hofmann’s method of synthesis, but the analyses do not verify with certainty who the inventors are because of the complexity of the dye mixtures.","PeriodicalId":15323,"journal":{"name":"Journal of Chemical Research","volume":"197 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":"135298313","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Alkyl-substituted testosterone derivatives are promising platforms for new drug discovery in medicinal chemistry. This approach provides a simple and efficient method for introducing an alkyl substituent to steroids at the C-4 position. In this study, the novel compound 3α-hydroxy-3β-methyl-4,4-dimethyl-5α-21-bromo-19-nor-pregnan-20-one is synthesized from 19-nor-testosterone. The protocol involves methylation of the dienolate, reduction of the alkene, the Grignard reaction of the carbonyl group, a Wittig reaction, hydroboration with BH 3 , the oxidation and bromination with a 49% overall yield. For the methylation and reduction steps, the effects of the base, solvent, and reactant ratio on the conversion and yield are investigated. The structures of the synthesized compounds are determined by nuclear magnetic resonance (NMR) and high-resolution mass spectrometry (HRMS) (electrospray ionization (ESI)).
{"title":"An α, β-unsaturated ketone alkylation and efficient reduction protocol for the synthesis of 3α-hydroxy-3β-methyl-4,4-dimethyl-5α-21-bromo-19-nor-pregnan-20-one","authors":"Mingguang Zhang, Wenlong Wang, Chen Guo, Chunhuan Jiang","doi":"10.1177/17475198231204213","DOIUrl":"https://doi.org/10.1177/17475198231204213","url":null,"abstract":"Alkyl-substituted testosterone derivatives are promising platforms for new drug discovery in medicinal chemistry. This approach provides a simple and efficient method for introducing an alkyl substituent to steroids at the C-4 position. In this study, the novel compound 3α-hydroxy-3β-methyl-4,4-dimethyl-5α-21-bromo-19-nor-pregnan-20-one is synthesized from 19-nor-testosterone. The protocol involves methylation of the dienolate, reduction of the alkene, the Grignard reaction of the carbonyl group, a Wittig reaction, hydroboration with BH 3 , the oxidation and bromination with a 49% overall yield. For the methylation and reduction steps, the effects of the base, solvent, and reactant ratio on the conversion and yield are investigated. The structures of the synthesized compounds are determined by nuclear magnetic resonance (NMR) and high-resolution mass spectrometry (HRMS) (electrospray ionization (ESI)).","PeriodicalId":15323,"journal":{"name":"Journal of Chemical Research","volume":"208 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":"135736724","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-07-03eCollection Date: 2023-07-01DOI: 10.1177/17475198231184799
Zhuxin She, Yinuo Yao, Conglong Wang, Yi Li, Xiaohui Xiong, Yuanyuan Liu
The COVID-19 pandemic caused by severe acute respiratory syndrome coronavirus 2 is a global health emergency. The main protease is an important drug target in coronaviruses. It plays an important role in the processing of viral RNA-translated polyproteins and is highly conserved in the amino acid sequence and three-dimensional structure, making it a good drug target for which several small molecule inhibitors are available. This paper describes the various anti-severe acute respiratory syndrome coronavirus 2 inhibitor drugs targeting Mpro discovered since the severe acute respiratory syndrome coronavirus 2 outbreak at the end of 2019, with all these compounds inhibiting severe acute respiratory syndrome coronavirus 2 Mpro activity in vitro. This provides a reference for the development of severe acute respiratory syndrome coronavirus 2 Mpro-targeted inhibitors and the design of therapeutic approaches to address newly emerged severe acute respiratory syndrome coronavirus 2 mutant strains with immune evasion capabilities.
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