Diastereoselective Synthesis and Conformational Analysis of (2<i>R</i>)- and (2<i>S</i>)-Fluorostatines: An Approach Based on Organocatalytic Fluorination of a Chiral Aldehyde

Hu, Xiang; Lawer, Aggie; Peterson, Matthew B.; Iranmanesh, Hasti; Ball, Graham E.; Hunter, Luke

doi:10.1021/acs.orglett.5b03592

Cited by 21 publications

(5 citation statements)

References 43 publications

(38 reference statements)

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“…The vicinal fluorohydrine moiety is a relevant unit in a series of valuable biomolecules such as amino acids, heterocyclic natural products and nucleosides [ 29 – 36 ]. Therefore, the fluorinated β-amino acid derivative (±)- 5 , obtained through transformation of (±)- 4 with chemodiscrimination of the alcoholic groups, might represent a promising bioactive framework.…”

Section: Resultsmentioning

confidence: 99%

Fluorination of some highly functionalized cycloalkanes: chemoselectivity and substrate dependence

Remete¹,

Nonn²,

Fustero³

et al. 2017

Beilstein J. Org. Chem.

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A study exploring the chemical behavior of some dihydroxylated β-amino ester stereo- and regioisomers, derived from unsaturated cyclic β-amino acids is described. The nucleophilic fluorinations involving hydroxy–fluorine exchange of some highly functionalized alicyclic diol derivatives have been carried out in view of selective fluorination, investigating substrate dependence, neighboring group assistance and chemodifferentiation.

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Section: Resultsmentioning

confidence: 99%

Fluorination of some highly functionalized cycloalkanes: chemoselectivity and substrate dependence

Remete¹,

Nonn²,

Fustero³

et al. 2017

Beilstein J. Org. Chem.

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“…Hunter and coworkers 129 have designed a diastereoselective synthesis of 2-(R) and 2-(S) fluorostatines represented in Scheme 47. employing FP-T300 6 (1-fluoro-2,4,6-trimethyl pyridinium triflate)…”

Section: -Methods For Fluorination Of Sugars and Nucleobase Derivatmentioning

confidence: 99%

“…128 As a result, the synthesis of both natural statines and their analogues has been a subject of intense interest. Hunter and coworkers 129 The rationale behind the special treatment in fluorinating techniques for amines is the decrease in their basicity upon intro-ducing a vicinal fluorine atom, and modulation of physicochemical characteristics, such as log P. Incorporation of the fluorine substituent at a late stage of transformation is also desirable. 130 Chen and Liu have very recently presented a review article on the methods for accessing β-fluoroamines.…”

Section: Carbon Atoms By Photocatalysismentioning

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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“…Acyclic non-aromatic motifs are the most prevalent in naturally occurring amino acids. Therefore, the ability to access either fluorinated analogues or completely novel acyclic motifs is of utmost importance for applications such as biological probes and peptide therapeutics [ [133] , [134] , [135] , [136] , [137] , [138] , [139] ]. There have been many reports of the synthesis of singly fluorinated analogues of naturally occurring acyclic amino acids [ 12 ].…”

Section: Complex Fluorine-containing Non-aromatic Amino Acidsmentioning

confidence: 99%