Enantioselective Michael Reaction of Acetals with Nitroalkenes: An Improvement of the Oseltamivir Synthesis

Tisovský, Pavol; Mečiarová, Mária; Šebesta, Radovan

doi:10.1021/acssuschemeng.5b01172

Cited by 11 publications

(4 citation statements)

References 27 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…However, this is not easy because some of the single reactions take a long time, and several hours and days are usually necessary to carry out several reactions. For instance, there are more than 60 syntheses , of (−)-oseltamivir phosphate (Tamiflu), a neuraminidase inhibitor, which is one of the most effective drugs for the treatment of influenza, and the total reaction time for the previous syntheses are more than 30 h. This number only includes the reaction time, and a much longer time is needed, considering the postprocessing operations. It is a great challenge to synthesize a molecule within a short time period in current synthetic organic chemistry.…”

mentioning

confidence: 99%

Time Economical Total Synthesis of (−)-Oseltamivir

Hayashi

Ogasawara

2016

Org. Lett.

View full text Add to dashboard Cite

A time economical 60 min total synthesis of (-)-oseltamivir was accomplished in a single reaction vessel over five steps. One of the key issues is reduction in the number of steps by eliminating lengthy reaction steps with substitution of a rapid epimerization step. A catalytic system consisting of three reagents, namely, diphenylprolinol silyl ether, thiourea, and acid, was developed for a rapid asymmetric Michael reaction with excellent diastereo- and enantioselectivities. All reactions were optimized in terms of not only yield and selectivity but also reaction time.

show abstract

mentioning

confidence: 99%

Time Economical Total Synthesis of (−)-Oseltamivir

Hayashi

Ogasawara

2016

Org. Lett.

View full text Add to dashboard Cite

show abstract

“…Pavol Tisovsky and co‐authors [79] designed a handy one‐pot process consisting of a three‐step arrangement namely, acetal deprotection reaction, Michael addition, and cyclization affording Oseltamivir skeleton. Step 1 involves Acetal 196 deprotection utilizing acidic ionic liquid [bmim]HSO 4 .…”

Section: Organocatalytic Enantioselective Michael Addition Reactionsmentioning

confidence: 99%

Enantioselective Organocatalytic Michael Addition Reactions Catalyzed by Proline/Prolinol/Supported Proline based Organocatalysts: An Overview

Pasuparthy

Maiti

2022

ChemistrySelect

View full text Add to dashboard Cite

Ever since the discovery of enantioselective organocatalytic Michael addition reactions, it has emerged as a significant path for synthesizing a variety of stereochemical products under mild conditions, also a prominent C−X (X=C, O, N, S) bond formation reaction in organic chemistry. Over time, substantial progress has been accomplished in diversity‐ and target‐ oriented asymmetric Michael addition reactions. This review provides a brief overview of the results, scope, and limitations of several influential strategies involving enantio‐selective Michael addition reactions promoted by mono‐functional proline/prolinol/supported‐proline‐based chiral organocatalysts. Furthermore, we also sincerely believe that the various synthetic strategies documented in this review will pave a pathway to improve the status of Michael addition reactions for synthesizing various drug molecules involving complex intermediates.

show abstract

“…2015 Tisovský synthesis [127] * Enantioselective Michael addition * Used acidic ionic liquid * One-pot operation * Cyclisation via HWE reaction 78.…”

Section: Sharpless Asymmetric Epoxidation-assisted Tamiflu Synthesismentioning

confidence: 99%

“…Tamiflu synthesis using enantioselective Michael addition reaction and ionic liquid: An improved method of Tamiflu synthesis by enantioselective Michael reaction has established by Tisovský with group members (Scheme 83). [127] Demasking of alkyloxyacetaldehyde acetal 432 in acidic ionic liquid, 1butyl-3-methylimidazolium hydrogen sulfate ([bmim]HSO 4 ) under microwave irradiation contribute compound 222. Stereoselective Michael addition to (Z)-N-(2-nitrovinyl) acetamide in the presence of catalyst 334 set to get a cyclized adduct 368 in high yield with syn:anti ratio of 74 : 26.…”

Section: Conflict Of Interestmentioning

confidence: 99%

Synthetic Advancement of Neuraminidase Inhibitor “Tamiflu”

2020

View full text Add to dashboard Cite

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.

show abstract

Enantioselective Michael Reaction of Acetals with Nitroalkenes: An Improvement of the Oseltamivir Synthesis

Cited by 11 publications

References 27 publications

Time Economical Total Synthesis of (−)-Oseltamivir

Time Economical Total Synthesis of (−)-Oseltamivir

Enantioselective Organocatalytic Michael Addition Reactions Catalyzed by Proline/Prolinol/Supported Proline based Organocatalysts: An Overview

Synthetic Advancement of Neuraminidase Inhibitor “Tamiflu”

Contact Info

Product

Resources

About