Aminodifluorosulfinium Salts: Selective Fluorination Reagents with Enhanced Thermal Stability and Ease of Handling<sup>,</sup>

L’Heureux, Alexandre; Beaulieu, Françis; Bennett, C. W.; Bill, David R.; Clayton, Simon; LaFlamme, François; Mirmehrabi, Mahmoud; Tadayon, Sam; Tovell, David J.; Couturier, Michel

doi:10.1021/jo100504x

Cited by 270 publications

(187 citation statements)

References 49 publications

(96 reference statements)

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“…They are used to convert alcohols to alkyl fluorides and carbonyl groups into gem-difluorides, being more selective than DAST and leading to fewer elimination side products [16]. Recently, several studies have been carried out to look for improved methods and substrates for nucleophilic fluorination reactions.…”

Section: Nucleophilic Methodsmentioning

confidence: 99%

Fluorinated Nucleosides as an Important Class of Anticancer and Antiviral Agents

et al. 2017

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Fluorine-containing nucleoside analogues represent a significant class of FDA approved chemotherapeutics widely used in the clinic. The incorporation of fluorine into drug-like agents modulates lipophilic, electronic and steric parameters thus influencing pharmacodynamic and pharmacokinetic properties of drugs. Fluorine can block oxidative metabolism of drugs and the formation of undesired metabolites by changing H-bonding interactions. In this review, we focus our attention on chemical fluorination reagents and methods used in the nucleoside analogues field, including PET radiochemistry. We briefly discuss both the cellular biology and clinical properties of FDA-approved and fluorine-containing nucleoside/nucleotide analogues in development as well as common resistance mechanisms associated with their use. Finally, we emphasize pro-nucleotide strategies used to improve therapeutic outcome of nucleoside analogues in the clinic.

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Section: Nucleophilic Methodsmentioning

confidence: 99%

Fluorinated Nucleosides as an Important Class of Anticancer and Antiviral Agents

et al. 2017

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“…It is not our aim Phenofluor 15 31 , PyFluor 16 32 and nickel-fluorido complexes 17a and 17b 33 together with (diethylamino)difluorosulfonium tetrafluoroborate 18 (XtalFluor-E). 34 . would be beneficial to the syntheses.…”

Section: Figure 1 Structures Of Atorvastatin Fluoxetin and Ciproflomentioning

confidence: 99%

Fluorination methods in drug discovery

2016

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Fluorination reactions of medicinal and biologically-active compounds will be discussed. Late stage fluorination strategies of medicinal targets have recently attracted considerable attention on account of the influence that the fluorine atom can impart to targets of medicinal importance, such as a modulation of lipophilicity, electronegativity, basicity and bioavailability, this latter as a consequence of membrane permeability. Therefore, the recourse to late-stage fluorine substitution on compounds with already known and relevant biological activity can provide the pharmaceutical industry with new leads with improved medicinal properties. The fluorination strategies will take into account different fluorinating reagents, nucleophilic, electrophilic and of radical nature. Diverse families of organic compounds such as (hetero)aromatic rings, and aliphatic substrates (sp 3 , sp 2 , and sp carbon atoms) will be studied in late-stage fluorination reaction strategies. The omniphobicity/lipophilicity and electrostatic interactions can be considered among the most prominent effects. Thus, introducing fluorine into an organic compound can significantly alter its biological properties.One other subtle but important effect of introducing fluorine into the backbone of a medicinal target is the inflection of acidity and basicity of the parent compound 4 , which can change, inter alia, the binding affinity, and bioavailability. Highly basic groups can have a detrimental effect on the bioavailability of a drug. Thus introducing a fluorine atom next to a basic group can reduce its basicity, enhancing its membrane permeability, and increasing bioavailability. Although the replacement of hydrogen for fluorine does not have a profound steric influence, electrostatic interactions with other groups can change conformations significantly. The replacement of hydrogen for fluorine on aromatic rings is a well-known strategy to decelerate oxidative metabolic processes by Cytochrome P450 monooxygenases. In this respect, the electron-withdrawing properties of fluorine on aromatic rings, which can slow down hydrolytic metabolism, alter reaction rates and stability of intermediates. Fluorine substitution on aromatic rings is also known to increase binding affinity, as a result of enhancing electrostatic interactions.However, it is difficult to predict the influence of fluorine substitution on the overall profile in a given situation.As numerous reports attest 1 , the number of marketed drugs that contain a fluorine atom has increased rapidly. As of 2009, the FDA-had approved >140 fluorine-containing drugs. This review article is intended to present new synthetic methodologies 9 for accomplishing fluorination reactions on molecules (drugs/prodrugs) with pharmacological activity. It is not our aim (Figure 3). would be beneficial to the syntheses. 3a.-Conversion of C Ar -H into C Ar -F BondsXu and co-workers 38 have developed an ortho C-H bond fluorination of 2-phenoxyl pyridine derivatives through a palladium-catalyzed reaction v...

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“…A Wittig-Horner reaction with ethyl diethylphosphoryl methanesulfonate afforded vinylsulfonate ester 6, which was cleaved by Bu4NI. The most efficient conversion of the resulting sulfonate salt (7) into the corresponding vinylsulfonyl fluoride (8) was achieved by using talFluor-M ® [14] in the presence of a catalytic amount of triethylamine trihydrofluoride acting as both a proton and fluoride source. [15] Two PVSF proteasome inhibitors (10 and 11, respectively) were obtained after cleavage of the Cbz-group from 8 followed by a coupling reaction with Cbz-Leu2-OH and Cbz-Leu3-OH using BOP.…”

Section: Chemistrymentioning

confidence: 99%

Proteasome inhibition by new dual warhead containing peptido vinyl sulfonyl fluorides

Brouwer

Álvarez

Ciaffoni

et al. 2016

Bioorganic & Medicinal Chemistry

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Aminodifluorosulfinium Salts: Selective Fluorination Reagents with Enhanced Thermal Stability and Ease of Handling^,

Cited by 270 publications

References 49 publications

Fluorinated Nucleosides as an Important Class of Anticancer and Antiviral Agents

Fluorinated Nucleosides as an Important Class of Anticancer and Antiviral Agents

Fluorination methods in drug discovery

Proteasome inhibition by new dual warhead containing peptido vinyl sulfonyl fluorides

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Aminodifluorosulfinium Salts: Selective Fluorination Reagents with Enhanced Thermal Stability and Ease of Handling,

Cited by 270 publications

References 49 publications

Fluorinated Nucleosides as an Important Class of Anticancer and Antiviral Agents

Fluorinated Nucleosides as an Important Class of Anticancer and Antiviral Agents

Fluorination methods in drug discovery

Proteasome inhibition by new dual warhead containing peptido vinyl sulfonyl fluorides

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Product

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Aminodifluorosulfinium Salts: Selective Fluorination Reagents with Enhanced Thermal Stability and Ease of Handling^,