- Azoacetylenes for the Synthesis of Arylazotriazole Photoswitches
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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.
- Anderl, Felix,Balkenhohl, Moritz,Carreira, Erick M.,Fink, Moritz,Pfaff, Patrick
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supporting information
p. 14495 - 14501
(2021/09/18)
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- FLOW SYNTHESIS PROCESS FOR THE PRODUCTION OF OSELTAMIVIR
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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.
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- Method for preparing oseltamivir phosphate by azide process
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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.
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- Modular click chemistry libraries for functional screens using a diazotizing reagent
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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.
- Meng, Genyi,Guo, Taijie,Ma, Tiancheng,Zhang, Jiong,Shen, Yucheng,Sharpless, Karl Barry,Dong, Jiajia
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- The hydrophobic side chain of oseltamivir influences type A subtype selectivity of neuraminidase inhibitors
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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.
- Lin, Xiong,Qin-Hua, Chen,Peng, Li,Chun-Lei, Li,Guang-De, Yang
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p. 105 - 115
(2017/10/06)
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- Novel compound, its synthetic method and therapeutic use (by machine translation)
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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.
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- A new and efficient asymmetric synthesis of oseltamivir phosphate (Tamiflu) from D-glucose
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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.
- Kongkathip, Boonsong,Akkarasamiyo, Sunisa,Kongkathip, Ngampong
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p. 2393 - 2399
(2015/03/30)
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- 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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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,
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Paragraph 0100
(2014/03/24)
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- PROCESS FOR THE PREPARATION OF OSELTAMIVIR AND METHYL 3-EPI-SHIKIMATE
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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.
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- Oseltamivir analogues bearing N-substituted guanidines as potent neuraminidase inhibitors
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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.
- Mooney, Caitlin A.,Johnson, Stuart A.,'T Hart, Peter,Quarles Van Ufford, Linda,De Haan, Cornelis A. M.,Moret, Ed E.,Martin, Nathaniel I.
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p. 3154 - 3160
(2014/05/06)
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- Facile method for the synthesis of oseltamivir phosphate
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A ten-step scheme for the preparation of an antiviral agent, ethyl (3R,4R,5S)-4-acetylamino-5-amino-3-(pent-3-yloxy)cyclohex-1-enecarboxylate phosphate, from (-)-shikimic acid was studied. The main parameters of the synthesis were determined and the optimal conditions for the preparation of the intermediate compounds were selected. The total yield of oseltamivir phosphate calculated based on (-)-shikimic acid was 27%.
- Kalashnikov,Sysolyatin,Sakovich,Sonina,Shchurova
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p. 163 - 170
(2013/11/19)
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- PROCESS FOR THE PREPARATION OF OSELTAMIVIR AND METHYL 3-EPI-SHIKIMATE
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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.
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- A new and efficient asymmetric synthesis of oseltamivir phosphate(Tamiflu) from D-mannose
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Oseltamivir phosphate (Tamiflu) was synthesized from D-mannose through a short and practical synthetic route. A unique feature of the route is that the bulky 3-pentyloxy group and adjacent acetamide of Tamiflu were introduced at an early stage of the synthesis by copper-catalyzed regioselective ringopening of the 2,3-pentylidene ketal of D-lyxofuranoside. The D-lyxofuranoside ethylphosphonate precursor was then cyclized via an intramolecular Horner-Wadsworth-Emmons reaction to furnish the Tamiflu skeleton.
- Chuanopparat, Nutthawat,Kongkathip, Ngampong,Kongkathip, Boonsong
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p. 6209 - 6211,3
(2012/12/11)
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- A novel and high-yielding asymmetric synthesis of oseltamivir phosphate (Tamiflu) starting from (-)-shikimic acid
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A novel and high-yielding asymmetric synthesis of oseltamivir phosphate 1 (Tamiflu) is described. The target compound 1 was obtained in 55% overall yield via an 11-step asymmetric synthesis starting from the naturally abundant (-)-shikimic acid. The present synthesis is characterized by some advantages such as the easy separation of intermediate 6 from triphenylphosphine oxide by using its large water-solubility, the use of inexpensive reagents throughout the synthesis, the lack of toxic heavy metals, mild reaction conditions and high yields for all steps. The stereochemical structure of the key intermediate 6 was unequivocally confirmed by X-ray crystallographic analysis.
- Nie, Liang-Deng,Ding, Wei,Shi, Xiao-Xin,Quan, Na,Lu, Xia
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p. 742 - 747
(2012/09/05)
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- Synthesis of the anti-influenza agent (-)-oseltamivir free base and (-)-methyl 3-epi-shikimate
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A new enantioselective synthesis of the anti-influenza agent (-)-oseltamivir free base (7.1% overall yield; 98% ee) and (-)-methyl 3-epi-shikimate (16% overall yield; 98% ee) has been described from readily available raw materials. Sharpless asymmetric epoxidation and diastereoselective Barbier allylation of an aldehyde are the key reactions employed in the incorporation of chirality, while the cyclohexene carboxylic ester core was constructed through a ring closing metathesis reaction.
- Rawat, Varun,Dey, Soumen,Sudalai, Arumugam
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p. 3988 - 3990
(2012/06/15)
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- Synthesis and in vitro study of novel neuraminidase inhibitors against avian influenza virus
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Evidences of oseltamivir resistant influenza patients raised the need of novel neuraminidase inhibitors. In this study, five oseltamivir analogs PMC-31-PMC-36, synthesised according to the outcomes of a rational design analysis aimed to investigate the effects of substitution at the 5-amino and 4-amido groups of oseltamivir on its antiviral activity, were screened for their inhibition against neuraminidase N1 and N3. The enzymes used as models were from the avian influenza A H7N1 and H7N3 viruses. The neuraminidase inhibition assay was carried out by using recombinant species obtained from a baculovirus expression system and the fluorogenic substrate MUNANA. The assay was validated by using oseltamivir carboxylate as a reference inhibitor. Among the tested compounds, PMC-36 showed the highest inhibition on N1 with an IC50 of 14.6 ± 3.0 nM (oseltamivir 25 ± 4 nM), while PMC-35 showed a significant inhibitory effect on N3 with an IC50 of 0.1 ± 0.03 nM (oseltamivir 0.2 ± 0.02 nM). The analysis of the inhibitory properties of this panel of compounds allowed a preliminary assessment of a structure-activity relationship for the modification of the 4-amido and 5-amino groups of oseltamivir carboxylate. The substitution of the acetamido group in the oseltamivir structure with a 2-butenylamido moiety reduced the observed activity, while the introduction of a propenylamido group was well tolerated. Substitution of the free 5-amino group of oseltamivir carboxylate with an azide, decreased the activity against both N1 and N3. When these structural changes were both introduced, a dramatic reduction of activity was observed for both N1 and N3. The alkylation of the free 5-amino group in oseltamivir carboxylate introducing an isopropyl group seemed to increase the inhibitory effect for both N1 and N3 neuraminidases, displaying a more pronounced effect against N1.
- Kongkamnerd, Jarinrat,Cappelletti, Luca,Prandi, Adolfo,Seneci, Pierfausto,Rungrotmongkol, Thanyada,Jongaroonngamsang, Nutthapon,Rojsitthisak, Pornchai,Frecer, Vladimir,Milani, Adelaide,Cattoli, Giovanni,Terregino, Calogero,Capua, Ilaria,Beneduce, Luca,Gallotta, Andrea,Pengo, Paolo,Fassina, Giorgio,Miertus, Stanislav,De-Eknamkul, Wanchai
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p. 2152 - 2157
(2012/05/05)
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- A new efficient synthesis of oseltamivir phosphate (Tamiflu) from (-)-shikimic acid
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New synthesis of oseltamivir phosphate was accomplished in 9 steps with a 27% overall yield from a readily available (-)-shikimic acid. Selective ring opening reaction of ketal and azide Mitsunobu reaction for facile replacement of a hydroxyl group by the N3 group at the C-3 position of (3R,4R,5R)-ethyl 4-hydroxy-5-(methoxymethoxy)-3-(pentan-3-yloxy)cyclohex-1-enecarboxylate 4 and at the C-4 position of (3R,4S,5R)-ethyl 4-acetamido-5-hydroxy-3-(pentan-3-yloxy) cyclohex-1-enecarboxylate 7 successfully served as the key steps.
- Kim, Hee-Kwon,Park, Kyoung-Joo Jenny
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p. 1561 - 1563
(2012/05/05)
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- Novel asymmetric synthesis of oseltamivir phosphate (Tamiflu) from (-)-shikimic acid via cyclic sulfite intermediates
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A novel asymmetric synthesis of oseltamivir phosphate 1 from the naturally abundant (-)-shikimic acid via 3,4-cyclic sulfite intermediate 3 (Scheme 1) is described. Target compound 1 was obtained in 39% overall yield from this nine-step synthesis, and the characteristic step of the synthesis is the regio- and stereospecific nucleophilic substitution with sodium azide at the allylic (C-3) position of 3,4-cyclic sulfite 3. Since the yield of the direct-aziridine-formation from the unprotected dihydroxyl azide 4 was not satisfactory, two improved preparations of the established compound 7 via protected 3,4-cyclic sulfites 10 and 13 (Scheme 2) have been developed. In these two improved preparations, compound 7 was obtained from 3,4-cyclic sulfite 3 in 7-steps in 64% or 62% overall yield, respectively. Copyright
- Nie, Liang-Deng,Shi, Xiao-Xin,Quan, Na,Wang, Fei-Feng,Lu, Xia
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experimental part
p. 1692 - 1699
(2012/01/02)
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- Sugar-based synthesis of tamiflu and its inhibitory effects on cell secretion
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Tamiflu is currently the most effective drug for the treatment of influenza, but the insufficient supply and side-effects of this drug demand urgent solutions. We present a practical synthesis of Tamiflu by using novel synthetic routes, cheap reagents, and the abundantly available starting material D-glucal. The strategy features a Claisen rearrangement of hexose to obtain the cyclohexene backbone and introduction of diamino groups through tandem intramolecular aziridination and ring opening. In addition, this synthetic protocol allows late-stage functionalization for the flexible synthesis of Tamiflu analogues. By using the synthesized Tamiflu and its active metabolite (oseltamivir carboxylate), we inves-tigated their influences on neuroendocrine PC12 cells in various aspects. It was discovered that oseltamivir carboxylate significantly inhibits the vesicular exocytosis (regulated secretion) of PC 12 cells, and suggests a mechanism underlying the Tamiflu side-effects, in particular its possible adverse influences on neurotransmitter release in the central nervous system.
- Ma, Jimei,Zhao, Yanying,Ng, Simon,Zhang, Jing,Zeng, Jing,Than, Aung,Chen, Peng,Liu, Xue-Wei
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supporting information; experimental part
p. 4533 - 4540
(2010/08/19)
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- SYNTHESIS OF OSELTAMIVIR CONTAINING PHOSPHONATE CONGENERS WITH ANTI-INFLUENZA ACTIVITY
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Novel phosphonate compounds are described. The compounds have activity as neuraminidase inhibitors against wild-type and H274Y mutant of H1N1 and H5N1 viruses. The present disclosure also provides an enantioselective synthetic route to known neuraminidase inhibitors oseltamivir and the anti-flu drug Tamiflu, as well as novel phosphonate compounds, via D-xylose. Another efficient and flexible synthesis of Tamiflu and the highly potent neuraminidase inhibitor Tamiphosphor was also achieved in 11 steps and > 20% overall yields from the readily available fermentation product (1S-cis)-3-bromo-3,5- cyclohexadiene-1,2-diol. Most of the reaction intermediates were obtained as crystals without tedious purification procedures. The key transformations include an initial regio- and stereoselective bromoamidation of a bromoarene cis- dihydrodiol, as well as the final palladium-catalyzed carbonylation and phosphonylation.
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Page/Page column 54-55
(2009/04/25)
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- METHOD OF FORMING OSELTAMIVIR AND DERIVATIVES THEREOF
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A process is provided for the synthesis of 4,5-diamino cyclohexene carboxylate ester (1): or a pharmaceutically acceptable salt thereof. R1 - R3 are a silyl-, an aliphatic, alicyclic, aromatic, arylaliphatic, or an arylalicyclic group. R4, R11 and R12 are H, a silyl-group, an aliphatic, alicyclic, aromatic, arylaliphatic, or an arylalicyclic group. 3,4-Dihydropyran compound (9): with R5 and R6 being suitable protecting groups, is reacted to form aldehyde (4): which is oxidized and converted to N-substituted carbamate (3): with R7 being a suitable protecting group. (3) is, via oxazolinidone (13): converted to azido carboxylate ester (2): and then to 4,5-diamino cyclohexene carboxylate ester (1).
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Page/Page column 44
(2009/07/18)
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- Preparation of oseltamivir phosphate
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The invention provides a new process for the conversion of shikimic acid to oseltamivir (I), and optionally to an acid addition salt, via the intermediate phosphoramide VII.
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Page/Page column 8-9
(2009/04/24)
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- PROCESS FOR OSELTAMIVIR PHOSPHATE
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The present invention provides an improved and commercially viable process for the preparation of oseltamivir phosphate. Thus, for example, ethyl (3R,4R,5S)-4-amino-5-azido-3-(1-ethylpropoxy)-1-cyclohexene-1-carboxylate is acetylated with acetic anhydride in methylene chloride in the presence of triethyl amine in the absence of water to give ethyl (3R,4R,5S)-4-(acetylamino)-5-azido-3-(1-ethylpropoxy)-1-cyclohexene-1-carboxylate.
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Page/Page column 3
(2009/07/02)
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- A short and practical synthesis of oseltamivir phosphate (tamiflu) from (-)-shikimic acid
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(Chemical Equation Presented) Oseltamivir phosphate (1) was synthesized from (-)-shikimic acid through a short and practical synthetic route via eight steps in 47% overall yield. In addition, the highly regioselective and stereoselective nucleophilic replacement of OMs by the N3 group in the third and seventh steps has been studied in detail, and the reaction conditions were optimized.
- Nie, Liang-Deng,Shi, Xiao-Xin,Kwang, Hyok Ko,Lu, Wei-Dong
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experimental part
p. 3970 - 3973
(2009/10/01)
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- A novel asymmetric synthesis of oseltamivir phosphate (Tamiflu) from (-)-shikimic acid
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Oseltamivir phosphate 1 was synthesized starting from a readily available acetonide, that is, ethyl (3R,4S,5R)-3,4-O-isopropylidene shikimate 2, through a new route via 11 steps and in 44% overall yield. The synthesis described in this article is characterized by two particular steps: the highly regioselective and stereoselective facile nucleophilic replacement of an OMs by an N3 group at the C-3 position of ethyl (3R,4S,5R)-3,4-O-bismethanesulfonyl-5-O-benzoyl shikimate 5, and the mild ring-opening of an aziridine with 3-pentanol at the C-1 position of ethyl (1S,5R,6S)-7-acetyl-5-benzoyloxy-7-azabicyclo[4,1,0]hept-2-ene-3-carboxylate 8.
- Nie, Liang-Deng,Shi, Xiao-Xin
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experimental part
p. 124 - 129
(2009/05/30)
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- A concise and flexible synthesis of the potent anti-influenza agents tamiflu and tamiphosphor
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(Chemical Equation Presented) Tamiflu and the highly potent neuraminidase inhibitor tamiphosphor have been synthesized in 11 steps and greater than 20% overall yields from an haloarene (1S,2S)-cis-diol. The key transformations include a regio- and stereoselective bromoamidation, and a palladium-catalyzed carbonylation or phosphonylation reaction (see scheme; tamiflu: A = CO 2Et, B = NH3+H2PO4 -, tamiphosphor: A = PO(ONH4)2, B = NH 2).
- Shie, Jiun-Jie,Fang, Jim-Min,Wong, Chi-Huey
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supporting information; experimental part
p. 5788 - 5791
(2009/03/11)
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- Preparation of oseltamivir phosphate (Tamiflu) and intermediates starting from D-glucose or D-xylose
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Novel processes for the preparation of the anti-viral agent, Oseltamivir Phosphate and novel intermediates prepared in such processes. The novel processes use as starting materials D-glucose or D-xylose in the preparation of Oseltamivir Phosphate.
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Page/Page column 10
(2010/11/29)
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- Synthesis of tamiflu and its phosphonate congeners possessing potent anti-influenza activity
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Using d-xylose as an appropriate chiral precursor, we have synthesized active neuraminidase inhibitor oseltamivir, antiflu drug Tamiflu, and novel phosphonate congeners that exhibit even stronger antiflu activities by inhibiting the neuraminidases of the wild-type and H274Y mutant of H1N1 and H5N1 viruses. Molecular modeling of the neuraminidase-phosphonate complex indicates a pertinent binding mode of the phosphonate with three arginine residues in the active site. Discovery of such potent neuraminidase inhibitors will offer an opportunity to the development of new anti-influenza drugs. Copyright
- Shie, Jiun-Jie,Fang, Jim-Min,Wang, Shi-Yun,Tsai, Keng-Chang,Cheng, Yih-Shyun E.,Yang, An-Suei,Hsiao, Shih-Chia,Su, Ching-Yao,Wong, Chi-Huey
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p. 11892 - 11893
(2008/03/27)
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- IMPROVED PROCESS FOR OSELTAMIVIR PHOSPHATE
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The present invention provides an improved and commercially viable process for the preparation of oseltamivir phosphate. Thus, for example, ethyl (3R,4R,5S)-4-amino-5-azido-3-(1-ethylpropoxy)-1-cyclohexene-1-carboxylate is acetylated with acetic anhydride in methylene chloride in the presence of triethyl amine in the absence of water to give ethyl (3R,4R,5S)-4-(acetylamino)-5-azido-3-(1-ethylpropoxy)-1-cyclohexene-1-carboxylate.
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Page/Page column 6-7
(2008/06/13)
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- Structure-activity relationship studies of novel carbocyclic influenza neuraminidase inhibitors
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A series of influenza neuraminidase inhibitors with the cyclohexene scaffold containing lipophilic side chains have been synthesized and evaluated for influenza A and B neuraminidase inhibitory activity. The size and geometry of side chains have been modified systematically in order to investigate structure-activity relationships of this class of compounds. The X-ray crystal structures of several analogues complexed with neuraminidase revealed that the lipophilic side chains bound to the hydrophobic pocket consisted of Glu276, Ala246, Arg224, and Ile222 of the enzyme active site. The structure-activity relationship studies of this series have also demonstrated remarkably different inhibitory potency between influenza A and B neuraminidase. This indicated that the lipophilic side chains had quite different hydrophobic interactions with influenza A and B neuraminidase despite their complete homology in the active site. Influenza B neuraminidase appeared to be much more sensitive toward the increased steric bulkiness of inhibitors compared to influenza A neuraminidase. From the extensive structure-activity relationship investigation reported in this article, GS 4071 emerged as one of the most potent influenza neuraminidase inhibitors against both influenza A and B strains.
- Kim, Choung U.,Lew, Willard,Williams, Matthew A.,Wu, Huiwei,Zhang, Lijun,Chen, Xiaowu,Escarpe, Paul A.,Mendel, Dirk B.,Laver, W. Graeme,Stevens, Raymond C.
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p. 2451 - 2460
(2007/10/03)
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