Recent synthetic approaches to oseltamivir phosphate (Tamiflu™) for the treatment of influenza

Magano, Javier

doi:10.1016/j.tet.2011.07.010

Cited by 65 publications

(49 citation statements)

References 173 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…These resulting O‐ and N‐containing cyclohexane frameworks are found in bioactive molecules of various families as exemplified by the species III – VI (Figure 1), and their stereoselective synthesis inevitably requires long procedures 11–15. Some 1,2‐diaminocyclitols ( III )12 are potent glucocerebrosidase activators and promising pharmacological chaperones for Gaucher disease.…”

Section: Conditions For the Oxidative Dimerizations Of 5 Amentioning

confidence: 99%

Copper‐Catalyzed Oxidative Dimerizations of 3‐N‐Hydroxy‐aminoprop‐1‐enes to form 1,4‐Dihydroxy‐2,3‐diaminocyclohexanes with C₂ Symmetry

Ghorpade¹,

Liu²

2014

Angewandte Chemie

View full text Add to dashboard Cite

This work describes the one‐step construction of complex and important molecular frameworks through copper‐catalyzed oxidations of cheap tertiary amines. Copper‐catalyzed aerobic oxidations of N‐hydroxyaminopropenes to form C2‐symmetric N‐ and O‐functionalized cyclohexanes are described. Such catalytic oxidations proceed with remarkable stereocontrol and high efficiency. Reductive cleavage of the two NO bonds of these products delivers 1,4‐dihydroxy‐2,3‐diaminocyclohexanes, which are important skeletons of several bioactive molecules.

show abstract

Section: Conditions For the Oxidative Dimerizations Of 5 Amentioning

confidence: 99%

Copper‐Catalyzed Oxidative Dimerizations of 3‐N‐Hydroxy‐aminoprop‐1‐enes to form 1,4‐Dihydroxy‐2,3‐diaminocyclohexanes with C₂ Symmetry

Ghorpade¹,

Liu²

2014

Angewandte Chemie

View full text Add to dashboard Cite

show abstract

“…The main issue is to construct the cyclohexene ring with multiple functional groups from cost-effective starting materials. As several comprehensive reviews [29][30][31][32][33][34] of these synthetic methods are available, we just discuss herein the various strategies applied in oseltamivir synthesis. The synthetic methods can be illustrated in six different approaches: (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.…”

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

View full text Add to dashboard Cite

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

show abstract

“…For example, several vicinal diamine-containing pharmaceuticals contain an additional contiguous oxygen-bearing chiral center (Figure 1). 4 In order to employ standard olefin oxidation protocols to accomplish the construction of these stereotriads, the substrates are required to bear a suitably protected substituent at the allylic position. This can inhibit the reactivity of the olefin or lead to mixtures of regioisomers when two different heteroatoms are introduced.…”

Section: Introductionmentioning

confidence: 99%

1,4-Diazaspiro[2.2]pentanes as a Flexible Platform for the Synthesis of Diamine-Bearing Stereotriads

et al. 2012

View full text Add to dashboard Cite

Nitrogen-containing stereotriads occur in a number of biologically active compounds, but general and flexible methods to access these compounds are limited mainly to the manipulation of chiral olefins. An alternative approach is to employ a highly chemo-, regio-, and stereocontrolled allene oxidation that can install a new carbon–heteroatom bond at each of the three original allene carbons. In this paper, an intramolecular/intermolecular allene bis-aziridination is described that offers the potential to serve as a key step for the construction of stereotriads containing vicinal diaminated motifs. The resultant 1,4-diazaspiro[2.2]pentane (DASP) scaffolds contain two electronically differentiated aziridines that undergo highly regioselective ring-openings at C1 with a variety of heteroatom nucleophiles to give chiral N,N-aminals. Alternatively, the same DASP intermediate can be induced to undergo a double ring opening reaction at both C1 and C3 to yield vicinal diaminated products corresponding to formal ring opening at C3. The chirality of a propargyl alcohol is easily transferred to the DASP with good fidelity, providing a new paradigm for the construction of enantioenriched nitrogen-containing stereotriads.

show abstract

Recent synthetic approaches to oseltamivir phosphate (Tamiflu™) for the treatment of influenza

Cited by 65 publications

References 173 publications

Copper‐Catalyzed Oxidative Dimerizations of 3‐N‐Hydroxy‐aminoprop‐1‐enes to form 1,4‐Dihydroxy‐2,3‐diaminocyclohexanes with C₂ Symmetry

Copper‐Catalyzed Oxidative Dimerizations of 3‐N‐Hydroxy‐aminoprop‐1‐enes to form 1,4‐Dihydroxy‐2,3‐diaminocyclohexanes with C₂ Symmetry

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

1,4-Diazaspiro[2.2]pentanes as a Flexible Platform for the Synthesis of Diamine-Bearing Stereotriads

Contact Info

Product

Resources

About

Recent synthetic approaches to oseltamivir phosphate (Tamiflu™) for the treatment of influenza

Cited by 65 publications

References 173 publications

Copper‐Catalyzed Oxidative Dimerizations of 3‐N‐Hydroxy‐aminoprop‐1‐enes to form 1,4‐Dihydroxy‐2,3‐diaminocyclohexanes with C2 Symmetry

Copper‐Catalyzed Oxidative Dimerizations of 3‐N‐Hydroxy‐aminoprop‐1‐enes to form 1,4‐Dihydroxy‐2,3‐diaminocyclohexanes with C2 Symmetry

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

1,4-Diazaspiro[2.2]pentanes as a Flexible Platform for the Synthesis of Diamine-Bearing Stereotriads

Contact Info

Product

Resources

About

Copper‐Catalyzed Oxidative Dimerizations of 3‐N‐Hydroxy‐aminoprop‐1‐enes to form 1,4‐Dihydroxy‐2,3‐diaminocyclohexanes with C₂ Symmetry

Copper‐Catalyzed Oxidative Dimerizations of 3‐N‐Hydroxy‐aminoprop‐1‐enes to form 1,4‐Dihydroxy‐2,3‐diaminocyclohexanes with C₂ Symmetry