Short Chemoenzymatic Azide‐Free Synthesis of Oseltamivir (Tamiflu): Approaching the Potential for Process Efficiency

Werner, Lukáš; Machara, Aleš; Hudlický, Tomáš

doi:10.1002/adsc.200900844

Cited by 66 publications

(21 citation statements)

References 41 publications

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“…Optically active 1,2-diols are valuable compounds as they can be transformed into several interesting molecules [ 1 , 2 , 3 ]. Due to their importance as building blocks in organic synthesis, a number of synthetic methodologies have been developed for their preparation [ 4 , 5 ].…”

Section: Introductionmentioning

confidence: 99%

Lipase Catalysed Kinetic Resolution of Racemic 1,2-Diols Containing a Chiral Quaternary Center

Gonzalo

2018

Molecules

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Optically active 1,2-diols are valuable buildings blocks in organic synthesis. In the present paper, a set of racemic 1,2-diols with an ester functional group are prepared, starting from α-ketoesters in a three-step procedure with moderate yields. The racemic 1,2-diols, containing a chiral quaternary center in their structure, are subjected to selective acylation in order to perform their kinetic resolution catalysed by a set of commercially available lipases. Under optimized reaction conditions, good conversions and enantioselectivities are achieved by using the lipase PSL-C from Pseudomonas cepacia in tert-butyl methyl ether. This biocatalyst could be reused up to five times without losing its properties.

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Section: Introductionmentioning

confidence: 99%

Lipase Catalysed Kinetic Resolution of Racemic 1,2-Diols Containing a Chiral Quaternary Center

Gonzalo

2018

Molecules

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“…20 These enantiopure cis-dihydrodiols are ideal synthetic precursors for cyclohexane based natural products, as every carbon in the ring is fully functionalised and the biotransformations can be easily scaled up. Therefore it is not surprising that these new chiral pool derivatives are being extensively used in the synthesis of natural products, 21 carbasugars, 22 active pharmaceutical ingredients 23 and as ligands in asymmetric catalysis. 24 Starting from dihydrodiol 1 our chemoenzymatic route to (−)-epibatidine is outlined (Scheme 1).…”

Section: Resultsmentioning

confidence: 99%

Chemoenzymatic formal synthesis of (−)- and (+)-epibatidine

Boyd¹,

Sharma²,

Kaik³

et al. 2012

Org. Biomol. Chem.

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“…Chemoenzymatic azide‐free synthesis of Tamiflu : Hudlicky and group published a third‐generation route to Tamiflu synthesis based on latent symmetry axis concept (Scheme ) . Allylic alcohol 245 was synthesised as per the previous strategy which underwent an [3,3] oxidative rearrangement in the presence of chromium oxide to afford enone 246 by Dauben–Michno oxidative transposition.…”

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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Short Chemoenzymatic Azide‐Free Synthesis of Oseltamivir (Tamiflu): Approaching the Potential for Process Efficiency

Abstract: A short chemoenzymatic and azide-free synthesis of oseltamivir was attained with the key steps consisting of a one-pot Dauben-Michno oxidative transposition and amination and a reductive transposition of an acrylate.

Cited by 66 publications

References 41 publications

Lipase Catalysed Kinetic Resolution of Racemic 1,2-Diols Containing a Chiral Quaternary Center

Lipase Catalysed Kinetic Resolution of Racemic 1,2-Diols Containing a Chiral Quaternary Center

Chemoenzymatic formal synthesis of (−)- and (+)-epibatidine

Synthetic Advancement of Neuraminidase Inhibitor “Tamiflu”

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