Helvetica Chimica Acta最新文献_第5页

Evolution of the Manufacturing Route towards a Key Benzothiophen-2-yl-Boronic Acid Building Block of Rogaratinib 罗加替尼的关键苯并噻吩-2-基硼酸结构单元生产工艺的演变

IF 1.8 4区化学

Helvetica Chimica Acta Pub Date : 2024-03-04 DOI: 10.1002/hlca.202400008

Jörg Gries, Johannes Platzek, Holger Paulsen

{"title":"Evolution of the Manufacturing Route towards a Key Benzothiophen-2-yl-Boronic Acid Building Block of Rogaratinib","authors":"Jörg Gries, Johannes Platzek, Holger Paulsen","doi":"10.1002/hlca.202400008","DOIUrl":"10.1002/hlca.202400008","url":null,"abstract":"The evolution of the synthesis of a benzothiophene-2-yl-boronic acid - a key building block for the anti-cancer agent Rogaratinib - is reported from multi-gram scale to industrialization. The pitfalls and learnings during process development are outlined, describing the optimization of the initial research synthesis route, investigation of an alternative approach based on a palladium-catalyzed Newman-Kwart rearrangement and finally changing the synthetic strategy from thiophene-construction to benzene-ring formation. Although the initial route was utilized to deliver material on kg-scale, the requirements for market-supply triggered the decision to pursue a new synthetic route. Catalyst costs, high purity-requirements, and not the least technical practicality caused the change to a synthesis with indeed higher step-count. However, this could be mitigated by repeated application of a telescoping approach. The free boronic acid was finally selected and manufactured as a stable isolated intermediate after challenges like proto-deboronation and trimerization to boroxine upon drying could be solved by an optimized crystallization procedure.","PeriodicalId":12842,"journal":{"name":"Helvetica Chimica Acta","volume":null,"pages":null},"PeriodicalIF":1.8,"publicationDate":"2024-03-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/hlca.202400008","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140033867","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Murielle F. Delley Murielle F. Delley

IF 1.8 4区化学

Helvetica Chimica Acta Pub Date : 2024-02-29 DOI: 10.1002/hlca.202400019

引用次数: 0

Revealing the Indispensable Role of the RFamide Functionality using a Novel Acid Labile Benzofuranone based Amine (ALBA) Linker 使用新型易酸苯并呋喃酮胺 (ALBA) 连接剂揭示 RFamide 功能的重要作用

IF 1.8 4区化学

Helvetica Chimica Acta Pub Date : 2024-02-25 DOI: 10.1002/hlca.202300204

Gemma Mudd, Megan Hendrikse, Steven Shave, Douglas R Houston, Robert P Millar, Manfred Auer

{"title":"Revealing the Indispensable Role of the RFamide Functionality using a Novel Acid Labile Benzofuranone based Amine (ALBA) Linker","authors":"Gemma Mudd, Megan Hendrikse, Steven Shave, Douglas R Houston, Robert P Millar, Manfred Auer","doi":"10.1002/hlca.202300204","DOIUrl":"10.1002/hlca.202300204","url":null,"abstract":"The RFamide family of peptides represents an important class of GPCR ligand neuropeptides covering a wide range of biological functions. While many analogues of the highly conserved C-terminal RFamide motif within this peptide class have been synthesized and their functional significance elucidated, additional exploration of the structure activity relationship is of value. We have developed a novel linker for solid phase peptide synthesis (SPPS) which is able to anchor amine functionalised compounds for further elaboration. The acid labile benzofuranone based amine (ALBA) linker (5-(3-aminopropylcarbamoyl)-2-[[tert-butyl(diphenyl)silyl]oxymethyl]benzoic acid) is compatible with Fmoc based SPPS and has two cleavage modes. As a proof of concept, the ALBA linker was used to successfully synthesise a novel analogue of Kisspeptin 10, the natural ligand for GPCR54, whereby the natural RFamide motif was replaced with an RFamine. Biological evaluation of the amine-containing analogue revealed that the group is not compatible with receptor activation.","PeriodicalId":12842,"journal":{"name":"Helvetica Chimica Acta","volume":null,"pages":null},"PeriodicalIF":1.8,"publicationDate":"2024-02-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/hlca.202300204","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139968805","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Synthesis and Quantitative Analysis of Glycans Conjugated to Gold Nanoparticles 与金纳米粒子共轭的聚糖的合成与定量分析

IF 1.8 4区化学

Helvetica Chimica Acta Pub Date : 2024-02-20 DOI: 10.1002/hlca.202300209

Kuo-Shiang Liao, Chih-Chuan Kung, Li-Chun Cheng, Cinya Chung, Chi-Huey Wong

{"title":"Synthesis and Quantitative Analysis of Glycans Conjugated to Gold Nanoparticles","authors":"Kuo-Shiang Liao, Chih-Chuan Kung, Li-Chun Cheng, Cinya Chung, Chi-Huey Wong","doi":"10.1002/hlca.202300209","DOIUrl":"10.1002/hlca.202300209","url":null,"abstract":"Nanoparticles, especially gold nanoparticles (GNPs) have emerged as promising tools for biomedical applications due to their unique properties and ability to be functionalized. However, quantitative analysis of biomolecules conjugated to nanoparticles remains a challenge. Here we report a method to conjugate a synthetic hybrid-type N-glycan to GNPs and quantitatively analyze the glycan content. The glycan was first conjugated to N-hydroxysuccinimide (NHS)-ester activated GNPs and confirmed qualitatively by Fourier-transform infrared spectroscopy and flow cytometry. The glycan conjugated-GNPs were then treated with neuraminidase to release terminal sialic acid from the glycan, which was labeled with 1,2-diamino-4,5-methylenedioxybenzene and quantitatively analyzed by Ultraperformance Liquid Chromatography (UPLC). The amount of the sialic acid released was equivalent to the glycan content on GNPs. This method enabled a precise quantification of glycans conjugated to gold nanoparticles and should facilitate its biomedical applications, including studies of multivalent receptor-glycan interaction, cell targeting and sorting, and immunization. Overall, this work provides an effective approach to synthesize and characterize nanoparticles conjugates.","PeriodicalId":12842,"journal":{"name":"Helvetica Chimica Acta","volume":null,"pages":null},"PeriodicalIF":1.8,"publicationDate":"2024-02-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139953814","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}

引用次数: 0

Andrea Vasella and the Active Site of Glycoside Hydrolases Andrea Vasella 和糖苷水解酶的活性位点

IF 1.8 4区化学

Helvetica Chimica Acta Pub Date : 2024-02-19 DOI: 10.1002/hlca.202300194

Roland Hoos-Michelotti

引用次数: 0

Cover Picture: (Helv. Chim. Acta 2/2024) 封面图片： (Helv. Chim. Acta 2/2024)

IF 1.8 4区化学

Helvetica Chimica Acta Pub Date : 2024-02-15 DOI: 10.1002/hlca.202470201

引用次数: 0

New Selective Inhibitors of α-Glucosidase for the Treatment of Type 2 Diabetes Mellitus 治疗 2 型糖尿病的新型α-葡萄糖苷酶选择性抑制剂

IF 1.8 4区化学

Helvetica Chimica Acta Pub Date : 2024-02-14 DOI: 10.1002/hlca.202300222

Takwa Khanchouch, Aurélie Vallin, Urjwan Alali, Mohammed Benazza, Rym Abidi, Véronique Bonnet

{"title":"New Selective Inhibitors of α-Glucosidase for the Treatment of Type 2 Diabetes Mellitus","authors":"Takwa Khanchouch, Aurélie Vallin, Urjwan Alali, Mohammed Benazza, Rym Abidi, Véronique Bonnet","doi":"10.1002/hlca.202300222","DOIUrl":"10.1002/hlca.202300222","url":null,"abstract":"Type 2 diabetes mellitus is a metabolic dreadful disease caused by an uncontrolled glucose level in the bloodstream, particularly high after a meal. Inhibitors of glucosidases, involved in the digestion of carbohydrates, can regulate this post-prandial increase in glucose concentration. The traditional drugs act as competitive inhibitors of both pancreatic α-amylase and α-glucosidases and this unselective inhibition is behind severe gastrointestinal side effects related to the concomitant inhibition of α-amylase. We described herein some perglycosylated cyclodextrins as efficient and selective inhibitors of α-glucosidase with low micromolar IC50 (3.64-7.98 μM) compared to the acarbose (IC50 212 μM), clinically used for patients suffering from type 2 diabetes. On the other hand, they do not inhibit α-amylase (IC50>500 μM). Structure/activity relationship rationalization suggests multiple interactions between the described inhibitors and α-glucosidase, which support the existence of both active site and allosteric interactions.","PeriodicalId":12842,"journal":{"name":"Helvetica Chimica Acta","volume":null,"pages":null},"PeriodicalIF":1.8,"publicationDate":"2024-02-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/hlca.202300222","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139770799","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

N-Methyl-N-Alkylaminocyclopentanes: Powerful and Selective β-d-Glucocerebrosidase Inhibitors N-甲基-N-烷基氨基环戊烷：强效、选择性β-D-葡糖脑抑制剂

IF 1.8 4区化学

Helvetica Chimica Acta Pub Date : 2024-02-13 DOI: 10.1002/hlca.202300219

Patrick Weber, Roland Fischer, Seyed A. Nasseri, Bettina M. Pabst, Herwig Prasch, Arnold E. Stütz, Martin Thonhofer, Stephen G. Withers, Werner Windischhofer, Tanja M. Wrodnigg

引用次数: 0

Development of a Novel Measurement Setup to Study and Predict Electrostatic Discharges in Agitated Glass-Lined Vessels 开发用于研究和预测搅拌搪玻璃容器中静电放电的新型测量装置

IF 1.8 4区化学

Helvetica Chimica Acta Pub Date : 2024-02-12 DOI: 10.1002/hlca.202300223

Benedikt Robert Brönnimann, Daniel Egli-Tedesco, Klaus Schwenzfeuer, Andreas Zogg

引用次数: 0

Benzylic C(sp3)‐H Azidation: Copper vs Iron Catalysis 苄基 C(sp3)-H 氮化：铜催化与铁催化

IF 1.8 4区化学

Helvetica Chimica Acta Pub Date : 2024-02-09 DOI: 10.1002/hlca.202400004

Angel Rentería-Gómez, Rubén O Torres-Ochoa, Pierre Palamini, Raphael Simonet-Davin, Qian Wang, J. Waser, Jieping Zhu

引用次数: 0