A Short and Practical Synthesis of Oseltamivir Phosphate (Tamiflu) from (−)-Shikimic Acid†

2009 ◽  
Vol 74 (10) ◽  
pp. 3970-3973 ◽  
Author(s):  
Liang-Deng Nie ◽  
Xiao-Xin Shi ◽  
Kwang Hyok Ko ◽  
Wei-Dong Lu
Keyword(s):  
Shikimic Acid ◽  
Practical Synthesis ◽  
Oseltamivir Phosphate

Continuous-Flow Synthesis of (–)-Oseltamivir Phosphate (Tamiflu)

Synlett ◽  
2020 ◽  
Vol 31 (19) ◽  
pp. 1925-1929 ◽  
Author(s):  
Paul Watts ◽  
Cloudius R. Sagandira
Keyword(s):  
Residence Time ◽  
Continuous Flow ◽  
Shikimic Acid ◽  
Flow Process ◽  
Flow Synthesis ◽  
Continuous Flow Process ◽  
The Individual ◽  
Total Residence Time ◽  
Oseltamivir Phosphate

Herein the anti-influenza drug (–)-oseltamivir phosphate is prepared in continuous flow from ethyl shikimate with 54% overall yield over nine steps and total residence time of 3.5 min from the individual steps. Although the procedure involved intermediate isolation, the dangerous azide chemistry and intermediates involved were elegantly handled in situ. It is the first continuous-flow process for (–)-oseltamivir phosphate involving azide chemistry and (–)-shikimic acid as precursor.

scholarly journals Cryptomeria japonica (L. F.) D. Don as source of shikimic acid

Revista Fitos ◽  
2020 ◽  
Vol 14 (4) ◽  
pp. 462-468
Author(s):  
Antonio Luiz Cerdeira ◽  
Sonia Claudia Nascimento Queiroz ◽  
Marcus Barifouse Matallo
Keyword(s):  
Influenza Virus ◽  
Glycoside Hydrolase ◽  
Cryptomeria Japonica ◽  
Potent Inhibitor ◽  
Shikimic Acid ◽  
Commercial Production ◽  
Virus H1n1 ◽  
Brand Name ◽  
Reliable Source ◽  
Oseltamivir Phosphate

Oseltamivir phosphate (OSP), marketed under the brand name of Tamiflu®, is a potent inhibitor of viral neuraminidase, a glycoside hydrolase enzyme essential for viral replication. OSP is also important to control influenza virus (H1N1) and is produced mainly from shikimic acid (SA) extracted from plants. The main source of SA is from seeds of I. verum. Alternatives to meet the worldwide demand are necessary. One of this is Cryptomeria japonica. In this study, we found a content of 56.36 mg.kg-1 of SA in dried biomass for C. japonica, while for I.verum, the traditional source, was 96.57 mg.kg-1. Due to the fact of C. japonica is a tree, exploited for commercial production, it can be a renewable and reliable source SA for OSP production.

Streamlined process for the esterification and ketalization of shikimic acid en route to the key precursor for oseltamivir phosphate (Tamiflu™)

2008 ◽  
Vol 10 (7) ◽  
pp. 743 ◽  
Author(s):  
Robert Carr ◽  
Frank Ciccone ◽  
Richard Gabel ◽  
Martin Guinn ◽  
David Johnston ◽  
...  
Keyword(s):  
Shikimic Acid ◽  
Oseltamivir Phosphate

Novel asymmetric synthesis of oseltamivir phosphate (Tamiflu) from (−)-shikimic acid via cyclic sulfite intermediates

2011 ◽  
Vol 22 (16-17) ◽  
pp. 1692-1699 ◽  
Author(s):  
Liang-Deng Nie ◽  
Xiao-Xin Shi ◽  
Na Quan ◽  
Fei-Feng Wang ◽  
Xia Lu
Keyword(s):  
Asymmetric Synthesis ◽  
Shikimic Acid ◽  
Cyclic Sulfite ◽  
Oseltamivir Phosphate

A novel and high-yielding asymmetric synthesis of oseltamivir phosphate (Tamiflu) starting from (−)-shikimic acid

2012 ◽  
Vol 23 (10) ◽  
pp. 742-747 ◽  
Author(s):  
Liang-Deng Nie ◽  
Wei Ding ◽  
Xiao-Xin Shi ◽  
Na Quan ◽  
Xia Lu
Keyword(s):  
Asymmetric Synthesis ◽  
Shikimic Acid ◽  
Oseltamivir Phosphate

scholarly journals Glyphosate on shikimic acid on Urochloa plantaginea

2020 ◽  
Vol 50 (9) ◽  
Author(s):  
Sydnei Dionisio Batista de Almeida ◽  
Daniel Andrade de Siqueira Franco ◽  
Antonio Luiz Cerdeira ◽  
Sonia Claudia do Nascimento de Queiroz ◽  
Marcus Barifouse Matallo
Keyword(s):  
Shikimic Acid ◽  
Strong Increase ◽  
Alternative Source ◽  
Limited Availability ◽  
Cosmetic Industry ◽  
Viral Inhibitor ◽  
Illicium Verum ◽  
Increasing Demand ◽  
Oseltamivir Phosphate

ABSTRACT: Shikimic acid (SA) has witnessed a strong increase in recent years due to the increasing demand of the pharmaceutical and cosmetic industry. The SA is used as a precursor for the synthesis of oseltamivir phosphate (Tamiflu®), a potent viral inhibitor and is extracted from the plant Illicium verum Hook which has a limited availability. This article proposed the use of Urochloa plantaginea (Link.) webster and glyphosate, as an alternative source of SA. U. plantaginea plants with 3 - 4 tillers and 4 - 6 leaves were harvest at 3, 6, 9 and 12 days after application (DAT) of low rates of glyphosate. Samples were dried, extracted, analyzed by HPLC and LC-MS/MS. The maximum SA concentrations were observed at 6 days after glyphosate at 36 g.a.e.ha-1 was applied in plants of U. plantaginea with 4 to 6 leaves. The capability of this annual gramineae to produce elevated SA levels throughout the entire biomass affords its potential for a greater yield on a per hectare basis.

scholarly journals Glyphosate as a tool to produce shikimic acid in plants

2014 ◽  
Vol 32 (3) ◽  
pp. 601-608 ◽  
Author(s):  
M.B. Matallo ◽  
S.D.B. Almeida ◽  
D.A.S. Franco ◽  
A.L. Cerdeira ◽  
D.L.P. Gazzeiro
Keyword(s):  
Shikimic Acid ◽  
Dry Mass ◽  
Climatic Conditions ◽  
Acid Biosynthesis ◽  
Acid Accumulation ◽  
Site Of Action ◽  
Soybean Plants ◽  
Alternative Sources ◽  
Oseltamivir Phosphate ◽  
Shikimic Acid Production

Oseltamivir phosphate is a potent viral inhibitor produced from shikimic acid extracted from seeds of Ilicium verum, the most important natural source. With the site of action 5-enolpyruvylshikimate-3-phosphate synthase (EPSP), glyphosate is the only compound capable of inhibiting its activity with the consequent accumulation of shikimic acid in plants. Corn and soybean plants were sprayed with reduced rates of glyphosate (0.0 to 230.4 g a.i. ha¹) and shikimic acid content in the dry mass was determined by HPLC 3, 7 and 10 days after application. Results showed shikimic acid accumulation in dry mass with increases of up to 969% in corn and 33,000% on soybeans, with peak concentrations 3 days after treatment (DAT). Industrial feasibility for shikimic acid production, combined with favorable climatic conditions for growing corn and soybean in virtually all over Brazil, favor the use of reduced rates of glyphosate in shikimic acid biosynthesis, with potential for use as an inducer in exploration of alternative sources for production of oseltamivir phosphate with low environmental impact.

A concise and practical synthesis of oseltamivir phosphate(Tamiflu) from d-mannose

Tetrahedron ◽  
2012 ◽  
Vol 68 (34) ◽  
pp. 6803-6809 ◽  
Author(s):  
Nutthawat Chuanopparat ◽  
Ngampong Kongkathip ◽  
Boonsong Kongkathip
Keyword(s):  
Practical Synthesis ◽  
Oseltamivir Phosphate
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