Synthesis of the anti-influenza agent (−)-oseltamivir free base and (−)-methyl 3-epi-shikimate

Rawat, Varun; Dey, Soumen; Sudalai, Arumugam

doi:10.1039/c2ob25635e

Cited by 19 publications

(8 citation statements)

References 36 publications

(2 reference statements)

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“…After that, compound 13j reacted with different amine, and K 2 CO 3 was used to neutralize hydrochloric acid, DMF as solvent. Finally, we got compound 13k~13t in yield from 61% to 78% …”

Section: Methodsmentioning

confidence: 99%

“…Finally, we got compound 13k~13t in yield from 61% to 78%. [31][32][33][34][35][36] 3 | RESULTS All 20 target compounds were evaluated for their NA inhibitory activities and selectivity using 2′-(4-methylumbellifery l)-α-D-acetylneuraminic acid (MUNANA) as the substrate. Then, crossed out N1 (H5N1) from group 1 and N2 (H3N2) from group 2 were selected as representatives for testing, and the results are summarized in Table 1.…”

Section: Chemistrymentioning

confidence: 99%

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The hydrophobic side chain of oseltamivir influences type A subtype selectivity of neuraminidase inhibitors

Xiong

Chen

et al. 2017

Chem Biol Drug Des

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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 IC = 0.1 ± 0.04 μm, H3N2 IC = 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.

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“…After that, compound 13j reacted with different amine, and K 2 CO 3 was used to neutralize hydrochloric acid, DMF as solvent. Finally, we got compound 13k~13t in yield from 61% to 78% …”

Section: Methodsmentioning

confidence: 99%

Section: Chemistrymentioning

confidence: 99%

The hydrophobic side chain of oseltamivir influences type A subtype selectivity of neuraminidase inhibitors

Xiong

Chen

et al. 2017

Chem Biol Drug Des

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“…Sharpless asymmetric epoxidation‐assisted Tamiflu synthesis : Rawat and the group members reported explored Sharpless asymmetric epoxidation (Scheme ) of 338 and oxidation of 339 followed by Barbier allylation with ethyl 2‐(bromomethyl)acrylate ( 341 ) to accomplish homoallylic alcohol 342 . Next target was hydroxy protection and removal of silyl ether and then oxidation (IBX/DMSO) to acquire labile aldehyde 343 .…”

Section: Common Synthetic Approachesmentioning

confidence: 99%

Synthetic Advancement of Neuraminidase Inhibitor “Tamiflu”

2020

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Tamiflu (oseltamivir phosphate), clinically working antiviral chiral drug, is most effective against the infectious disease caused by both influenza A and B. It is also the last resort drug for the treatment of N1H1 virus infection at a high cost with minimal global availability. The current industrial method uses natural (‐)‐shikimic acid obtained from Chinese star anise and coffee beans, hence the limited natural resource and scarcity restricted the Tamiflu production. While most of the synthetic methods reported were composed of natural chiral pools and relatively low‐cost reagents, however, the industrial process is fundamentally limited to the use of hazardous azide or tedious purification methods. In case of an influenza outbreak, producing the Tamiflu according to its demand may be difficult. This document detailed the synthetic progress of chemistry over the last two decades emphasizing the starting materials, hazards of reagents, time needed, number of steps, and overall yields etc. for the interest in academia as well as industrial research.

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“…Another approach to the synthesis of oseltamivir is based on a ring formation by a metatesis reaction. This strategy was applied by Sudalai and coworkers using cis -1,4-butene diol ( 147 ) as the starting material (Scheme 19) [101]. 147 was monosilylated with TBSCl and then treated with tert-butyl hydroperoxide (TBHP) in presence of (−)-DET to give the epoxide 148 .…”

Section: Oseltamivirmentioning

confidence: 99%

Influenza Neuraminidase Inhibitors: Synthetic Approaches, Derivatives and Biological Activity

2016

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Despite being a common viral disease, influenza has very negative consequences, causing the death of around half a million people each year. A neuraminidase located on the surface of the virus plays an important role in viral reproduction by contributing to the release of viruses from infected host cells. The treatment of influenza is mainly based on the administration of neuraminidase inhibitors. The neuraminidase inhibitors zanamivir, laninamivir, oseltamivir and peramivir have been commercialized and have been demonstrated to be potent influenza viral neuraminidase inhibitors against most influenza strains. In order to create more potent neuraminidase inhibitors and fight against the surge in resistance resulting from naturally-occurring mutations, these anti-influenza drugs have been used as templates for the development of new neuraminidase inhibitors through structure-activity relationship studies. Here, we review the synthetic routes to these commercial drugs, the modifications which have been performed on these structures and the effects of these modifications on their inhibitory activity.

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Synthesis of the anti-influenza agent (−)-oseltamivir free base and (−)-methyl 3-epi-shikimate

Cited by 19 publications

References 36 publications

The hydrophobic side chain of oseltamivir influences type A subtype selectivity of neuraminidase inhibitors

The hydrophobic side chain of oseltamivir influences type A subtype selectivity of neuraminidase inhibitors

Synthetic Advancement of Neuraminidase Inhibitor “Tamiflu”

Influenza Neuraminidase Inhibitors: Synthetic Approaches, Derivatives and Biological Activity

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