Chemball(Hangzhou) Chemicals Ltd’s Post

Spasmolytic Activity, Anti-Inflammatory Potential, and Molecular Docking Studies of Anthranilic Acid Hybrids M Milusheva, V Gledacheva, I Stefanova, Mehran Feizi-Dehnayebi, M Todorova, ... Chemical and Materials Sciences - Developments and Innovations chapter 8 3 … https://lnkd.in/dMYhQq-i

𝑻𝒉𝒆 𝑹𝒐𝒖𝒕𝒆 𝑵𝒐𝒕 𝑻𝒂𝒌𝒆𝒏 - 𝑬𝒑𝒊𝒔𝒐𝒅𝒆 13 #ChemAIRS explored diverse synthetic approaches to develop a tetrahydrobenzoazepine scaffold, a critical intermediate in the synthesis of #BIIB091, Biogen's investigational small-molecule therapy for multiple sclerosis. Our proposed synthetic routes focused on the construction of the benzazepine core as an N-Boc-protected ketone. Diverging from Biogen's reported synthesis, which utilized an amine transaminase (#ATA) biocatalytic approach to establish the benzylic amine stereocenter, 𝐶ℎ𝑒𝑚𝐴𝐼𝑅𝑆 𝑝𝑟𝑜𝑝𝑜𝑠𝑒𝑑 𝑎𝑛 𝑎𝑙𝑡𝑒𝑟𝑛𝑎𝑡𝑖𝑣𝑒 𝑚𝑒𝑡ℎ𝑜𝑑 𝑖𝑛𝑣𝑜𝑙𝑣𝑖𝑛𝑔 𝑟𝑒𝑑𝑢𝑐𝑡𝑖𝑣𝑒 𝑎𝑚𝑖𝑛𝑎𝑡𝑖𝑜𝑛. This protocol employed ammonium acetate (NH₄OAc) and sodium cyanoborohydride (NaBH₃CN) in isopropanol (𝑖PrOH) as a more conventional synthetic route.  To achieve the key benzazepine framework, ChemAIRS identified three distinct synthetic strategies: 1️⃣ 𝐅𝐫𝐢𝐞𝐝𝐞𝐥-𝐂𝐫𝐚𝐟𝐭𝐬 (𝐅-𝐂) 𝐀𝐜𝐲𝐥𝐚𝐭𝐢𝐨𝐧 (Schemes 1 and 2): The F-C acylation served as the critical ring-forming step, though it proved challenging, with modest yields reported by Biogen. ChemAIRS proposed optimized reaction conditions to improve this transformation (Figure 2). Additionally, the algorithm flagged potential side reactions that could compromise the cyclization efficiency (Figure 3), providing insights into reaction optimization. 2️⃣ 𝐈𝐧𝐭𝐫𝐚𝐦𝐨𝐥𝐞𝐜𝐮𝐥𝐚𝐫 𝐏𝐝-𝐂𝐚𝐭𝐚𝐥𝐲𝐳𝐞𝐝 𝐇𝐞𝐜𝐤 𝐑𝐞𝐚𝐜𝐭𝐢𝐨𝐧 (Scheme 3): ChemAIRS proposed an alternative cyclization via an intramolecular Heck reaction, utilizing Pd catalysts. The system also identified a range of catalyst options to fine-tune this transformation for improved yield and selectivity (Figure 4). 3️⃣ 𝐄𝐬𝐭𝐞𝐫-𝐀𝐫𝐲𝐥 𝐇𝐚𝐥𝐢𝐝𝐞 𝐂𝐲𝐜𝐥𝐢𝐳𝐚𝐭𝐢𝐨𝐧 (Scheme 4): A third approach involved cyclization through the reaction of a corresponding ester with an aryl iodide, offering another viable strategy for the formation of the benzazepine core. By combining computational insights with chemical expertise, ChemAIRS highlighted these pathways as 𝑣𝑖𝑎𝑏𝑙𝑒 𝑠𝑦𝑛𝑡ℎ𝑒𝑡𝑖𝑐 𝑠𝑡𝑟𝑎𝑡𝑒𝑔𝑖𝑒𝑠, 𝑜𝑓𝑓𝑒𝑟𝑖𝑛𝑔 𝑓𝑙𝑒𝑥𝑖𝑏𝑖𝑙𝑖𝑡𝑦 in addressing the challenges of benzazepine core construction. #tetrahydrobenzoazepine #BTK_inhibitor #multiple_sclerosis #retrosynthesis #FriedelCrafts_acylation #Heck_reaction

#BIIB091, a highly potent and reversible inhibitor of Bruton’s tyrosine kinase (#BTK), is being developed by 𝐁𝐢𝐨𝐠𝐞𝐧 as a promising small-molecule therapeutic for multiple sclerosis (#MS). #ChemAIRS evaluated multiple synthetic pathways to construct the #tetrahydrobenzoazepine scaffold, a crucial structural intermediate integral to the production of BIIB091.

Enantioselective Synthesis of Tri-Axis Naphthalenes Author: Catharina Goedecke Axially chiral compounds can be useful, e.g., in chiral materials or drug discovery. Synthesizing axially chiral molecules with multiple stereogenic axes could significantly expand the chemical space covered by this type of compound. However, the catalytic stereoselective preparation of axially chiral molecules with more than two axes connected to a single benzene ring has remained challenging so far. Quan Cai, Fudan University, Shanghai, China, and colleagues have developed a method for the synthesis of triaxially chiral polysubstituted naphthalene derivatives (general structure pictured). The team’s approach is based on a sequence consisting of a Ni(II)-catalyzed Diels–Alder reaction of isobenzofurans and a triflic acid (TfOH)-promoted dehydrative aromatization reaction. They used 1,3-biarylisobenzofuran derivatives and β-aryl-substituted α,β-unsaturated N-acyl pyrazoles as reaction partners in a modular approach. Via this approach, the researchers obtained a series of axially chiral naphthalene derivatives with three stereogenic axes on one benzene ring (pictured in red) with excellent enantioselectivities and diastereoselectivities. The team successfully performed the reaction on the gram scale, obtaining the desired product in a yield of 76 % and with 92 %[ee]. As an example of potential uses in chiroptical organic materials, they prepared a circularly polarized luminescence (CPL)-active dye with a good luminescence dissymmetry factor and high fluorescence quantum efficiency. Enantioselective Synthesis of Atropisomeric Tri‐Axis Naphthalenes via Diels–Alder Reaction and Dehydrative Aromatization of Isobenzofurans, Yuan-Bo Du, Qi-Tao Lu, Yun-Shu Cui, Kai-Wen Wu, Yu Wang, Yu-Zhen Zhang, Zheng Zhao, Jun-Li Hou, Quan Cai, Angew. Chem. Int. Ed. 2024. https://lnkd.in/dKbZXWZa

Exploring the Therapeutic Potential of Pergularia daemia: Synthesis and Characterization of Zinc Oxide Nanoparticles Read the Article here: https://bit.ly/3MbJdHD #Characterization #Nanoparticles #phytochemicals #Pergulariadaemia #Zincoxide #chemistry #biochemistry #nanomaterial #analyticalchemistry #chemicalengineering #Phytochemicals #ChemicalSciences #ChemicalTechnology

Scientific discoveries can often be catalyzed by industry-academic discussion. In this case, it fruits to a publication in Nature Catalysis! Our team in collaboration with scientists from RWTH Aachen University and AstraZeneca published this article "A general strategy for the amination of electron-rich and electron-poor heteroaromatics by desaturative catalysis" to overcome the limitations in convention methods to introduce alkylamines onto heteroaromatics. By using saturated heterocyclic ketones as aryl surrogates for desaturative coupling with amines, we demonstrated that the reaction can be operated under mild photochemical conditions, is compatible with complex amines, and delivers wider scope of heteroaromatics that are difficult to access by other methods. Read the article here for more insight: https://lnkd.in/dSFirwpk Thanks to our collaborators Daniele Leonori and Alessandro Ruffoni from The Institute of Organic Chemistry at RWTH Aachen University.

Join us July 30th at 10am ET! Our own, Charles Chase will be diving into a conversation titled, "Fragment-Based Oligonucleotide and Oligopeptide Synthesis." 🔗 to register: https://okt.to/6jLgh8 . Advancements towards fragment-based approaches for oligonucleotide and oligopeptide synthesis will be presented. Leveraging Asymchem's expertise in synthetic chemistry, continuous processing, and enzyme engineering/biotransformation, we have developed an innovative liquid/solid phase hybrid synthesis platform using oligomer-fragments to manufacture complex oligonucleotides and peptides. Advantages, scope and limitations of fragment-based manufacturing methods, and the comparison to traditional solid-phase or liquid synthesis approaches, will be presented. . #oligonucleotide #peptides

FastClick™ Click Reagents: New Fluorescent Labels Now Available for biomolecular labeling in mild conditions 📢 ✔️ 32 options available in new series ✔️ contains both the CAG moiety of FastClick (for assisting click efficiency) and a fluorophore (as the tag) for developing fluorescent probes ✔️ Enhances the yield and reaction speed of copper-catalyzed azide-alkyne cycloaddition (CuAAC) reaction ✔️ Improved biocompatibility—no external copper chelator required check it out https://lnkd.in/gm-ZcNeK #biotech #biochemistry #molecular

Researchers at the Institute of Chemical Research of Catalonia (ICIQ) have developed a new metal-free method for synthesizing cyclic molecules, crucial for drug design. This method improves on the old Hofmann-Löffler-Freytag (HLF) mechanism by using hexafluoro-2-propanol (HFIP) as a solvent, enabling single-electron transfer to form C(sp³)–N bonds. This innovative approach allows for the efficient creation of six-membered rings like piperidine, overcoming the limitations of traditional HLF methods. This breakthrough is documented in *Nature Synthesis*. For more details, visit Phys.org: https://lnkd.in/ePJGpaan

Here is our latest pre-print focusing on the scaled up enzymatic synthesis of 2'deoxy nucleoside analogues. We explore the reaction scope of nucleoside transglycosylase II and demonstrate the scalability of the process to prepare high value nucleoside building blocks. We also establish a structural basis of the mechanism of transglycosylation which proceeds via covalent catalysis. This was collaborative work with Gideon Grogan and Alex Ascham (York), and Admir Salihovic Andrea Taladriz Sender and Paul Hoskisson Strathclyde Faculty of Science Work was funded by BBSRC The Leverhulme Trust #chemicalbiology #oligonucleotide #biocatalysis