An Efficient Stereoselective Total Synthesis of All Stereoisomers of the Antibiotic Thiamphenicol through Ruthenium‐Catalyzed Asymmetric Reduction by Dynamic Kinetic Resolution

Perez, Marc; Echeverria, Pierre‐Georges; Martinez-Arripe, Elsa; Zoubir, Mehdi Ez; Touati, Ridha; Zhang, Zhaoguo; Genêt, Jean‐Pierre; Phansavath, Phannarath; Ayad, Tahar; Ratovelomanana‐Vidal, Virginie

doi:10.1002/ejoc.201500661

Cited by 36 publications

(26 citation statements)

References 97 publications

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“…Unsurprisingly, the rational of semi-synthesis, that of chemically manipulating a scaffold, applies to a fully synthetic antibiotic like chloramphenicol. In fact, replacing the nitro group with methanesulfonyl resulted in thiamphenicol in 1952, which overcame the most concerning toxicity issues and had greater antimicrobial effect, thereby improving its clinical application [66]. The discovery in 1953 of the natural product azomycin found little clinical application but introduced the nitroimidazole class.…”

Section: From the Ground Up: Fully Synthetic Antibioticsmentioning

confidence: 99%

Antibiotic Discovery: Where Have We Come from, Where Do We Go?

2019

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Given the increase in antibiotic-resistant bacteria, alongside the alarmingly low rate of newly approved antibiotics for clinical usage, we are on the verge of not having effective treatments for many common infectious diseases. Historically, antibiotic discovery has been crucial in outpacing resistance and success is closely related to systematic procedures—platforms—that have catalyzed the antibiotic golden age, namely the Waksman platform, followed by the platforms of semi-synthesis and fully synthetic antibiotics. Said platforms resulted in the major antibiotic classes: aminoglycosides, amphenicols, ansamycins, beta-lactams, lipopeptides, diaminopyrimidines, fosfomycins, imidazoles, macrolides, oxazolidinones, streptogramins, polymyxins, sulphonamides, glycopeptides, quinolones and tetracyclines. During the genomics era came the target-based platform, mostly considered a failure due to limitations in translating drugs to the clinic. Therefore, cell-based platforms were re-instituted, and are still of the utmost importance in the fight against infectious diseases. Although the antibiotic pipeline is still lackluster, especially of new classes and novel mechanisms of action, in the post-genomic era, there is an increasingly large set of information available on microbial metabolism. The translation of such knowledge into novel platforms will hopefully result in the discovery of new and better therapeutics, which can sway the war on infectious diseases back in our favor.

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Section: From the Ground Up: Fully Synthetic Antibioticsmentioning

confidence: 99%

Antibiotic Discovery: Where Have We Come from, Where Do We Go?

2019

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“…All four stereoisomers of the antibiotic thiamphenicol [112] that exhibits activity on numerous Gram‐positive and Gram‐negative pathogens, were readily prepared by using as the key step Ru‐catalyzed asymmetric hydrogenation (Scheme 41) or hydrogen transfer reactions (not shown) of an α‐amido β‐keto ester through DKR [113] …”

Section: Synthetic Applicationsmentioning

confidence: 99%

Asymmetric Hydrogenation: Design of Chiral Ligands and Transition Metal Complexes. Synthetic and Industrial Applications.

Genêt

Phansavath

Ratovelomanana‐Vidal

2021

Israel Journal of Chemistry

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This personal account focuses on the development of atropisomeric ligands and chiral transition metal complexes and their applications to the asymmetric hydrogenation of alkenes, ketones and heteroaromatics using Ru(II) and Ir(III) catalysts in‐house developed. Particularly, effective scaled‐up development syntheses of SYNPHOS and DIFLUORPHOS have been successfully achieved and their steric and electronic profiling established. Going further, we demonstrated the utility of such homogeneous catalytic process highlighted with examples of industrial applications and total syntheses of biorelevant targets. Asymmetric hydrogenation provides a powerful tool for performing precise stereocontrolled transformations on valuable complex molecules.

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“…In 2015, we developed the total synthesis of all four stereoisomers of thiamphenicol 47 ; a broad‐spectrum bacteriostatic antibiotic industrially prepared by chemical resolution that is commonly used in veterinary or aquacultural practice 31. The key step of our synthesis involved Ru‐catalyzed AH and asymmetric transfer hydrogenation (ATH) of an easily accessible racemic α‐amido β‐ketoester derivative 45 through a DKR process to establish the essential syn or anti relationship of compounds (2 S ,3 R )‐ 46 /(2 R ,3 S )‐ 46 and (2 R ,3 R )‐ 46 /(2 S ,3 S )‐ 46 , respectively (Scheme ) 32…”

Section: Asymmetric Hydrogenation (Ah)mentioning

confidence: 99%

Transition‐Metal‐Catalyzed Asymmetric Hydrogenation and Transfer Hydrogenation: Sustainable Chemistry to Access Bioactive Molecules

Ayad

Phansavath

Ratovelomanana‐Vidal

2016

The Chemical Record

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Over the last few decades, the development of new and highly efficient synthetic methods to obtain chiral compounds has become an increasingly important and challenging research area in modern synthetic organic chemistry. In this account, we review recent work from our laboratory toward the synthesis of valuable chiral building blocks through transition-metal-catalyzed asymmetric hydrogenation and transfer hydrogenation of C=O, C=N and C=C bonds. Application to the synthesis of biologically relevant products is also described.

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An Efficient Stereoselective Total Synthesis of All Stereoisomers of the Antibiotic Thiamphenicol through Ruthenium‐Catalyzed Asymmetric Reduction by Dynamic Kinetic Resolution

Cited by 36 publications

References 97 publications

Antibiotic Discovery: Where Have We Come from, Where Do We Go?

Antibiotic Discovery: Where Have We Come from, Where Do We Go?

Asymmetric Hydrogenation: Design of Chiral Ligands and Transition Metal Complexes. Synthetic and Industrial Applications.

Transition‐Metal‐Catalyzed Asymmetric Hydrogenation and Transfer Hydrogenation: Sustainable Chemistry to Access Bioactive Molecules

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