Improved enantioselective gram scale synthesis route to N-Fmoc-protected monofluoroethylglycine

Leppkes, Jakob; Hohmann, Thomas; Koksch, Beate

doi:10.1016/j.jfluchem.2020.109453

Cited by 14 publications

(14 citation statements)

References 25 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…34 Thus, we have recently reported an improved synthetic strategy to obtain the fluorinated amino acid (2S)-4-monofluoroethylglycine (MfeGly) at the gram scale. 35 Moreover, Soloshonok et al developed a general and practical synthetic process to obtain enantiomerically pure Fmoc-protected fluorinated amino acid through an asymmetric and Ni(II)-complex mediated stereoselective synthesis (see scheme S1 in the supporting information). [36][37][38][39] In current attempts, we have extended this strategy to the synthesis of a diverse range of aliphatic fluorinated amino acids with different side chain patterns.…”

Section: Introductionmentioning

confidence: 99%

Rational design of amphiphilic fluorinated peptides: evaluation of self-assembly properties and hydrogel formation

et al. 2022

Self Cite

View full text Add to dashboard Cite

show abstract

Section: Introductionmentioning

confidence: 99%

Rational design of amphiphilic fluorinated peptides: evaluation of self-assembly properties and hydrogel formation

et al. 2022

Self Cite

View full text Add to dashboard Cite

show abstract

“…With respect to the amount of the amino acids employed, this result was found to be highly advantageous, since the fluorinated aliphatic amino acids are not commercially available and require extensive efforts in organic synthesis. 20,34,35 [a] Yields represent obtained purified lyophilized protein.…”

Section: Full-length Synthesis and Refolding Of Bpti Variantsmentioning

confidence: 99%

Fluorine-induced polarity increases inhibitory activity of BPTI towards chymotrypsin

Leppkes

Dimos

Loll

et al. 2022

Preprint

Self Cite

View full text Add to dashboard Cite

Substituting the P1 position in bovine pancreatic trypsin inhibitor (BPTI) is known to heavily influence its inhibitory activity towards serine proteases. Side-chain fluorinated aliphatic amino acids have been shown to alter numerous properties of peptides and proteins and thus are of interest in the context of BPTI. In our study, we systematically investigated the site-specific incorporation of non-canonical amino acids into BPTI by microwave-assisted solid-phase peptide synthesis (SPPS). Inhibitor activity of the variants was tested towards the serine protease α-chymotrypsin. We observed enhanced inhibition of two fluorinated BPTIs compared to wild type and hydrocarbon variants. To further investigate the complexes, we performed x-ray structure analysis. Our findings underline the power fluorine offers as a tool in protein engineering to beneficially alter the effects on phenomena as protein-protein interactions.

show abstract

“…[MfeGly], and difluoroethylglycine 3 [DfeGly] ( Different synthetic methods were published in the last years to obtain the described compounds. [15][16][17][18][19][20][21][22][23][24][25][26][27][28] However, the described approaches are multi-step syntheses that require several chromatographic purification steps and follow different synthetic strategies. In addition, most of these amino acids could only be isolated on a milligram-scale.…”

Section: Introductionmentioning

confidence: 99%

Gram-scale asymmetric synthesis of fluorinated amino acids using a chiral nickel(II) complex

Hohmann

Dyrks

Chowdhary

et al. 2022

Preprint

Self Cite

View full text Add to dashboard Cite

Fluorinated amino acids play an important role in the field of peptide and protein engineering. Although several different syntheses have been published in recent decades, obtaining fluorinated amino acids on a gram-scale still poses a challenge. Furthermore, the described pathways to obtain fluorinated amino acids are based on different synthetic strategies, making a uniform approach from similar starting materials highly interesting. Chiral Ni(II) complexes were introduced as powerful tools in the synthesis of non-canonical amino acids. In this work, we present a strategy for the synthesis of a diverse range of fluorinated amino acids from the corresponding Ni(II) complex on a gram-scale from which the products can be obtained in enantiopure form (>94%ee). In addition, we describe syntheses for alkyl iodide building blocks which are required for the alkylation reactions with the corresponding Ni(II) complex. Finally, we characterized the synthesized fluorinated amino acids with regard to their hydrophobicity and α-helix propensity.

show abstract

Improved enantioselective gram scale synthesis route to N-Fmoc-protected monofluoroethylglycine

Cited by 14 publications

References 25 publications

Rational design of amphiphilic fluorinated peptides: evaluation of self-assembly properties and hydrogel formation

Rational design of amphiphilic fluorinated peptides: evaluation of self-assembly properties and hydrogel formation

Fluorine-induced polarity increases inhibitory activity of BPTI towards chymotrypsin

Gram-scale asymmetric synthesis of fluorinated amino acids using a chiral nickel(II) complex

Contact Info

Product

Resources

About