Fluorodehydroxylation, a novel method for synthesis of fluoroamines and fluoroamino acids

Kollonitsch, J.; Marburg, Stephen; Perkins, Leroy M.

doi:10.1021/jo01319a023

Cited by 78 publications

(40 citation statements)

References 3 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…The configuration of 1 (and, there-fore, that of 2, its ester), as the diastereoisomer of 6 is described in Ref. 7. As the + and ,J(HF) values are very close together for 1 and 6, the assignment of configuration by other methods than x-ray analysis is very difficult.…”

Section: ~~~~~~ ~mentioning

confidence: 99%

Fluoro‐α‐amino acids. 1—use of ¹⁹F NMR spectroscopy for the configurational determination of β‐fluoro‐α‐amino acids through complexation by 18‐crown‐6 ether

Hamman¹,

Salon²,

Béguin³

1982

Org. Magn. Reson.

View full text Add to dashboard Cite

Erythro and threo configurational assignments have been made for 11 p-fluoro-a-amino acids or esters using the effect of complexation of the ammonium group by 18-crown-6 ether on the '9 NMR parameters. For the erythro con6gurations, 'J(tFF) increases and a high-field ' % chemical shift is generally observed; these phenomena are accompanied by a decrease in 'J(J3H) and 3J(CF). The opposite effects are observed for the threo configurations. These observations can be explained by a change in the relative population of the conformers around the C,-C, bond on complexation of the ammonium group. This complexation impairs the interactions between the ammonium and fluorine groups and, concomitantly, the steric hindrance between the ammonium and R (methyl, phenyl or carboxylate) groups is increased.

show abstract

Section: ~~~~~~ ~mentioning

confidence: 99%

Fluoro‐α‐amino acids. 1—use of ¹⁹F NMR spectroscopy for the configurational determination of β‐fluoro‐α‐amino acids through complexation by 18‐crown‐6 ether

Hamman¹,

Salon²,

Béguin³

1982

Org. Magn. Reson.

View full text Add to dashboard Cite

show abstract

“…[13,15,16] We therefore set out to adapt the methods that were used by Charvillon and Amouroux to synthesize the two d-isomers of 3-fluoroaspartate for synthesis of the corresponding l-erythroand l-threo isomers, that is, (2R,3R)-and (2R,3S)-3-fluoroaspartic acid (4 and 8, respectively). [17] First, we used l-diethyl tartrate (l-DET) instead of d-DET as a starting material in the synthesis of both isomers, so as to effect the required change in chirality at the a carbon.…”

Section: Resultsmentioning

confidence: 99%

3‐Fluoroaspartate and Pyruvoyl‐Dependant Aspartate Decarboxylase: Exploiting the Unique Characteristics of Fluorine To Probe Reactivity and Binding

Villiers¹,

Koekemoer²,

Strauss³

2010

Chemistry A European J

View full text Add to dashboard Cite

Fluorine-containing amino acids have been used with great success as mechanism-based inhibitors of pyridoxal phosphate (PLP)-dependent enzymes, and the influence of fluorine on the conformation of molecules has also been extensively studied and practically exploited. In this study, we sought to use these unique characteristics to probe the reactivity and binding of aspartate decarboxylase (ADC) enzymes, which are members of the small class of pyruvoyl-dependant decarboxylases. Since ADC activity has been shown to be essential to the virulence of Mycobacterium tuberculosis, information gained in this manner could be used for the development of inhibitors that selectively target pyruvoyl-dependent enzymes such as ADC, without affecting PLP-dependent enzymes in the host. For this purpose, we synthesized the L-erythro and L-threo isomers of 3-fluoroaspartate and tested their ability to act as substrates and/or inhibitors of the M. tuberculosis and Escherichia coli ADC enzymes. Trapping and MS-based binding analysis was additionally used to confirm that both isomers enter the enzymes' active sites. Our studies show that both isomers undergo single turnover decarboxylation and fluorine elimination reactions to give enamine products that can be trapped within the active site. Interestingly, the enamine/ADC complex that forms from the L-erythro (but not the L-threo) isomer is sufficiently stable that it can be observed even without any trapping. This finding suggests that the two 3-fluoroaspartates maintain different conformations within the ADC active site, which leads to the enamine products with configurations of different stabilities. Taken together, our results provide new insights for the development of cofactor-specific inhibitors, and confirm the utility of fluorine as a unique tool for probing reactivity and binding profiles within enzymes.

show abstract

“…Scheme 4. Fluorodehydroxyation in the side chain of serine could be effected with little racemization through treatment with SF 4 in liquid HF at low temperature. [25,26] In view of the extremely corrosive natures of SF 4 and HF, it was necessary and important to develop a new methodology to access chiral 3-fluoroalanine. Hoveyda's group [27] …”

Section: Monofluorinated α-Amino Acidsmentioning

confidence: 99%

Recent Advances in the Synthesis of Fluorinated Amino Acids

2011

View full text Add to dashboard Cite

Introduction of fluorine atoms or fluorine‐containing groups into amino acids has attracted much attention from bioorganic and medicinal chemists because the resulting fluorinated amino acids have found wide application as potential enzyme inhibitors and antitumor (antibacterial) agents. Additionally, it is well known that replacement of naturally occurring amino acid(s) in some peptide chains with their fluorinated counterparts can significantly increase specific protein–ligand or protein–protein interactions, leading to increases in the proteolytic and thermal stabilities of peptide compounds and, as a result, promote their therapeutic properties. This microreview summarizes important advances in the synthesis of fluorinated amino acids since 2005. The contents are simply divided into three groups on the basis of amino acid types: fluorinated α‐amino acids (F‐αAAs), fluorinated β‐amino acids (F‐βAAs), and fluorinated cyclic amino acids (F‐CAAs).

show abstract

Fluorodehydroxylation, a novel method for synthesis of fluoroamines and fluoroamino acids

Cited by 78 publications

References 3 publications

Fluoro‐α‐amino acids. 1—use of ¹⁹F NMR spectroscopy for the configurational determination of β‐fluoro‐α‐amino acids through complexation by 18‐crown‐6 ether

Fluoro‐α‐amino acids. 1—use of ¹⁹F NMR spectroscopy for the configurational determination of β‐fluoro‐α‐amino acids through complexation by 18‐crown‐6 ether

3‐Fluoroaspartate and Pyruvoyl‐Dependant Aspartate Decarboxylase: Exploiting the Unique Characteristics of Fluorine To Probe Reactivity and Binding

Recent Advances in the Synthesis of Fluorinated Amino Acids

Contact Info

Product

Resources

About

Fluorodehydroxylation, a novel method for synthesis of fluoroamines and fluoroamino acids

Cited by 78 publications

References 3 publications

Fluoro‐α‐amino acids. 1—use of 19F NMR spectroscopy for the configurational determination of β‐fluoro‐α‐amino acids through complexation by 18‐crown‐6 ether

Fluoro‐α‐amino acids. 1—use of 19F NMR spectroscopy for the configurational determination of β‐fluoro‐α‐amino acids through complexation by 18‐crown‐6 ether

3‐Fluoroaspartate and Pyruvoyl‐Dependant Aspartate Decarboxylase: Exploiting the Unique Characteristics of Fluorine To Probe Reactivity and Binding

Recent Advances in the Synthesis of Fluorinated Amino Acids

Contact Info

Product

Resources

About

Fluoro‐α‐amino acids. 1—use of ¹⁹F NMR spectroscopy for the configurational determination of β‐fluoro‐α‐amino acids through complexation by 18‐crown‐6 ether

Fluoro‐α‐amino acids. 1—use of ¹⁹F NMR spectroscopy for the configurational determination of β‐fluoro‐α‐amino acids through complexation by 18‐crown‐6 ether