204255-06-1Relevant articles and documents
Azoacetylenes for the Synthesis of Arylazotriazole Photoswitches
Anderl, Felix,Balkenhohl, Moritz,Carreira, Erick M.,Fink, Moritz,Pfaff, Patrick
supporting information, p. 14495 - 14501 (2021/09/18)
We report a modular approach toward novel arylazotriazole photoswitches and their photophysical characterization. Addition of lithiated TIPS-acetylene to aryldiazonium tetrafluoroborate salts gives a wide range of azoacetylenes, constituting an underexplored class of stable intermediates.In situdesilylation transiently leads to terminal arylazoacetylenes that undergo copper-catalyzed cycloadditions (CuAAC) with a diverse collection of organoazides. These include complex molecules derived from natural products or drugs, such as colchicine, taxol, tamiflu, and arachidonic acid. The arylazotriazoles display near-quantitative photoisomerization and long thermalZ-half-lives. Using the method, we introduce for the first time the design and synthesis of a diacetylene platform. It permits implementation of consecutive and diversity-oriented approaches linking two different conjugants to independently addressable acetylenes within a common photoswitchable azotriazole. This is showcased in the synthesis of several photoswitchable conjugates, with potential applications as photoPROTACs and biotin conjugates.
FLOW SYNTHESIS PROCESS FOR THE PRODUCTION OF OSELTAMIVIR
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, (2020/09/27)
This invention provides for a flow synthesis process for producing Oseltamivir and pharmaceutically acceptable salts thereof from shikimic acid in particular but not exclusively to a flow synthesis process for producing Oseltamivir phosphate from shikimic acid in a nine-step flow synthesis that provides for superior reaction times and product yields compared to known methods.
Method for preparing oseltamivir phosphate by azide process
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, (2020/10/20)
The invention belongs to the field of pharmaceutical chemicals, and particularly relates to a method for preparing oseltamivir phosphate by an azide process. The method comprises the following steps:reacting a compound shown in a formula (III) with sodium azide and ammonium chloride, opening a nitrogen heterocyclic ring, performing acetylation, reducing an azide group, removing tert-butyl, salifying with phosphoric acid, and purifying to obtain pure oseltamivir phosphate shown in a formula (I). According to the method, diallylamine with strong corrosivity and expensive palladium acetate do not need to be used so that the enterprise cost is reduced.
Modular click chemistry libraries for functional screens using a diazotizing reagent
Meng, Genyi,Guo, Taijie,Ma, Tiancheng,Zhang, Jiong,Shen, Yucheng,Sharpless, Karl Barry,Dong, Jiajia
, p. 86 - 89 (2019/11/13)
Click chemistry is a concept in which modular synthesis is used to rapidly find new molecules with desirable properties1. Copper(i)-catalysed azide–alkyne cycloaddition (CuAAC) triazole annulation and sulfur(vi) fluoride exchange (SuFEx) catalysis are widely regarded as click reactions2–4, providing rapid access to their products in yields approaching 100% while being largely orthogonal to other reactions. However, in the case of CuAAC reactions, the availability of azide reagents is limited owing to their potential toxicity and the risk of explosion involved in their preparation. Here we report another reaction to add to the click reaction family: the formation of azides from primary amines, one of the most abundant functional groups5. The reaction uses just one equivalent of a simple diazotizing species, fluorosulfuryl azide6–11 (FSO2N3), and enables the preparation of over 1,200 azides on 96-well plates in a safe and practical manner. This reliable transformation is a powerful tool for the CuAAC triazole annulation, the most widely used click reaction at present. This method greatly expands the number of accessible azides and 1,2,3-triazoles and, given the ubiquity of the CuAAC reaction, it should find application in organic synthesis, medicinal chemistry, chemical biology and materials science.
The hydrophobic side chain of oseltamivir influences type A subtype selectivity of neuraminidase inhibitors
Lin, Xiong,Qin-Hua, Chen,Peng, Li,Chun-Lei, Li,Guang-De, Yang
, p. 105 - 115 (2017/10/06)
Neuraminidase, which plays a critical role in the influenza virus life cycle, is a target for new therapeutic agents. The study of structure–activity relationships revealed that the C-5 position amino group of oseltamivir was pointed to 150-cavity of the neuraminidase in group 1. This cavity is important for selectivity of inhibitors against N1 versus N2 NA. A serial of influenza neuraminidase inhibitors with the oseltamivir scaffold containing lipophilic side chains at the C-5 position have been synthesized and evaluated for their influenza neuraminidase inhibitory activity and selectivity. The results indicated that compound 13o (H5N1 IC50?=?0.1?±?0.04?μm, H3N2 IC50?=?0.26?±?0.18?μm) showed better inhibitory activity and selectivity against the group 1 neuraminidase. This study may provide a clue to design of better group 1 neuraminidase inhibitors.
Novel compound, its synthetic method and therapeutic use (by machine translation)
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, (2016/10/07)
Novel compounds are described. The compounds generally comprise an acidic group, a basic group, a substituted amino or N-acyl and a group having an optionally hydroxylated alkane moiety. Pharmaceutical compositions comprising the inhibitors of the invention are also described. Methods of inhibiting neuraminidase in samples suspected of containing neuraminidase are also described. Antigenic materials, polymers, antibodies, conjugates of the compounds of the invention with labels, and assay methods for detecting neuraminidase activity are also described.
A new and efficient asymmetric synthesis of oseltamivir phosphate (Tamiflu) from D-glucose
Kongkathip, Boonsong,Akkarasamiyo, Sunisa,Kongkathip, Ngampong
, p. 2393 - 2399 (2015/03/30)
Abstract The anti-influenza drug, oseltamivir phosphate (Tamiflu) was synthesized from d-glucose via a novel and efficient synthetic route. A unique feature of the synthesis is that the key intermediate aziridine cyclohexene was synthesized as a mixture of diastereomers, via a metal-mediated domino reaction and ring closing metathesis (RCM). The iodoxylose compound was prepared in 9 steps from d-glucose. Both isomers of aziridine cyclohexene intermediate could be converted into Tamiflu via two pathways. First, both isomers of aziridine cyclohexene underwent aziridine-ring opening yielded diastereomeric of 1,2-amino mesylate cyclohexene esters. The trans-1,2-amino mesylate isomer could be transformed to tamiflu by formation of aziridine then regio- and stereoselective nucleophilic substitution of the azide to afford 1,2-amino azido compound whereas the cis-isomer could be transformed directly by SN2 substitution of azide to give the same azido product, which then converted into oseltamivir phosphate.
Oseltamivir analogues bearing N-substituted guanidines as potent neuraminidase inhibitors
Mooney, Caitlin A.,Johnson, Stuart A.,'T Hart, Peter,Quarles Van Ufford, Linda,De Haan, Cornelis A. M.,Moret, Ed E.,Martin, Nathaniel I.
, p. 3154 - 3160 (2014/05/06)
A series of oseltamivir analogues bearing an N-substituted guanidine unit were prepared and evaluated as inhibitors of neuraminidases from four strains of influenza the two most potent analogues identified contain relatively small N-guanidine substituents (N-methyl and N-hydroxyl) and display enhanced inhibition with IC50 values in the low nanomolar range against neuraminidases from wild-type and oseltamivir-resistant strains. Potential advantages of including the N-hydroxyguanidine moiety in neuraminidase inhibitors are also discussed.
PROCESS FOR THE PREPARATION OF OSELTAMIVIR AND METHYL 3-EPI-SHIKIMATE
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, (2014/09/03)
The present invention discloses high yielding enantioselective process for synthesis of Oseltamivir from readily available starting material, cis-1,4-butene diol. The process features incorporation of chirality using sharpless asymmetric epoxidation (AE) and diastereoselective Barbier allylation and construction of cyclohexene carboxylic acid ester core through a ring closing metathesis (RCM) reaction. Further also disclosed herein is synthesis of (?)-methyl 3-epi-shikimate.
METHOD FOR PREVENTING OR TREATING ARRHYTHMIA, METHOD FOR PREVENTING OR TREATING ATRIAL FIBRILLATION, MODEL OF SUSTAINED ATRIAL FIBRILLATION, METHOD FOR PRODUCING THE MODEL, AND METHOD FOR SCREENING FOR ATRIAL FIBRILLATION INHIBITOR
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, (2014/03/24)
A method for preventing or treating atrial fibrillation, including: administering, to an individual, an atrial fibrillation inhibitor containing a compound expressed by one of the following Structural Formulas (I) to (VI) or a pharmacologically acceptable salt thereof: where in the Structural Formula (III), Gluc refers to glucuronic acid,
