Synthesis of (–)‐Oseltamivir by Using a Microreactor in the Curtius Rearrangement

Ishikawa, Hayato; Bondžić, Bojan P.; Hayashi, Yujiro

doi:10.1002/ejoc.201100074

Cited by 51 publications

(38 citation statements)

References 71 publications

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“…The approach to 2 also uses a nitro group as an amine precursor, but flow methodology is not employed for that step. The procedure has been modified to use a flow reaction for the Curtius rearrangement starting from the acid chloride intermediate 3 (Scheme 18) (79).…”

Section: Scheme 15 Preparation Of Amines From Azidesmentioning

confidence: 99%

Managing Hazardous Reactions and Compounds in Process Chemistry

Ager¹

2014

ACS Symposium Series

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Section: Scheme 15 Preparation Of Amines From Azidesmentioning

confidence: 99%

Managing Hazardous Reactions and Compounds in Process Chemistry

Ager¹

2014

ACS Symposium Series

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“…Finally, acid/base extraction provided (À)-oseltamivir (119). The synthesis was completed by employing two one-pot reaction sequences with a total yield of 60% [83][84][85][86].…”

Section: Synthesis Of Oseltamivirmentioning

confidence: 99%

Diarylprolinol Silyl Ethers: Development and Application As Organocatalysts

Gotoh

Hayashi

2013

Sustainable Catalysis

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“…53 His team also utilized microflow reactor to perform the Curtius rearrangement, followed by trapping with acetic acid, as a safe manner for large-scale synthesis. 54 The one-pot strategy for oseltamivir synthesis was also accomplished by Ma and coworkers, 55 using (Z)-Nacetyl-2-nitroethanamine (75) in lieu of (E)-2-nitroacrylate as the acceptor in asymmetric Michael reaction with aldehyde 71 (Scheme VB). Lu and coworkers 56 have used an asymmetric aza-Henry reaction of sulfinyl aldimine 78, followed by a tandem Michael-Wittig reaction in oseltamivir synthesis (Scheme VC).…”

Section: Synthesis Of Oseltamivirmentioning

confidence: 99%

Phosphonate Congeners of Oseltamivir and Zanamivir as Effective Anti‐influenza Drugs: Design, Synthesis and Biological Activity

Shie

Fang

2013

J Chinese Chemical Soc

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Influenza is a long-standing health problem. We review here the recent development of neuraminidase inhibitors for influenza treatment. Tamiflu, the phosphate salt of oseltamivir, is an orally available neuraminidase inhibitor designed to have a cyclohexene scaffold to mimic the structure of the oxoniumlike intermediate in the enzymatic cleavage of the terminal sialoside from cell receptor. Many new synthetic procedures of oseltamivir without using shikimic acid have been explored because the current industrial manufacture of tamiflu may have problem in shortage of shikimic acid for global supply during influenza pandemics. In these shikimate-independent syntheses, six different approaches have been utilized to construct the multiple substituted cyclohexene ring: (i) using existing six-membered rings, (ii) construction by Diels-Alder reactions, (iii) construction by intramolecular aldol, Dieckmann and Wittig reactions, (iv) construction by tandem Michael-Wittig reactions, (v) construction by olefin metathesis, and (vi) construction by Claisen rearrangement. Phosphonate group is generally used as a bioisostere of carboxylate in drug design. The syntheses of tamiphosphor and zanaphosphor, which are the phosphonate congeners of oseltamivir and zanamivir, were recently accomplished and shown to possess potent inhibitory activities against avian and human influenza viruses, including the oseltamivir-resistant strain, according to the neuraminidase inhibition, cell-based assay and mice experiments. For the first time, phosphonate monoalkyl esters are proved to be real active drugs, but not prodrugs of the parental phosphonic acids. This review covers the design, synthesis and biological activity of phosphonate compounds as effective anti-influenza agents. Sinica, since 2003. His current interests are organic synthesis and chemical biology, including new synthetic methods, asymmetric catalysis, biomolecular recognition, natural products and drug discovery. Scheme I Outline of the current method for tamiflu manufacture Scheme II Outline of the methods using the existing six-membered rings for oseltamivir synthesis Shie and Fang Scheme V Outline of oseltamivir synthesis involving tandem Michael-Wittig reactions Scheme VI Outline of oseltamivir synthesis involving ring-closure metathesis reaction Scheme VII Outline of oseltamivir synthesis involving Claisen rearrangement Scheme VIII Synthesis of tamiphosphor from D-xylose Scheme IX Synthesis of tamiphosphor and guanidinotamiphosphor from bromobenzene Scheme X Synthesis of tamiphosphor from tamiflu or tamiflu precursor Scheme XI Synthesis of zanamivir from sialic acid Scheme XII Synthesis of zanamivir from D-gluconod-lactone Lipophilicity of oseltamivir phosphonate congenersLipophilicity is an important factor for the pharmacokinetics behavior of drugs. The partition coefficient (P) of Scheme XIII Synthesis of zanamivir via asymmetric nitroaldol reaction Scheme XIV Synthesis of amino-danaphosphor and zanaphosphor from sialic acid

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Synthesis of (–)‐Oseltamivir by Using a Microreactor in the Curtius Rearrangement

Cited by 51 publications

References 71 publications

Managing Hazardous Reactions and Compounds in Process Chemistry

Managing Hazardous Reactions and Compounds in Process Chemistry

Diarylprolinol Silyl Ethers: Development and Application As Organocatalysts

Phosphonate Congeners of Oseltamivir and Zanamivir as Effective Anti‐influenza Drugs: Design, Synthesis and Biological Activity

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