Abstract
The perfluoroheteroaromatic reagent pentafluoropyridine has proved to be a highly reactive electrophile, undergoing SNAr arylation reactions in the presence of a range of nucleophilic peptide side chains (i.e. cysteine, tyrosine, serine and lysine) under mild conditions. Moreover, we have shown how one-step peptide-modification using perfluoroheteroaromatics can deliver enhanced proteolytic stability in pharmaceutically-relevant peptides such as oxytocin.
Highlights
Perfluoroheteroaromatic derivatives such as pentafluoropyridine [1], tetrafluoro-pyrimidine [2] and tetrafluoropyridazine [3] are highly useful building blocks for organic synthesis because, in principle, all fluorine atoms may be displaced by nucleophiles via regioselective, sequential nucleophilic aromatic substitution reactions (SNAr)
As part of an ongoing wider research programme in perfluoroheterocyclic chemistry, we previously reported that orthogonally protected serine derivatives can be successfully arylated with pentafluoropyridine [1] to afford novel amino acids such as 4, which could be utilised as a building block in peptide synthesis8a (Fig. 2)
Pentafluoropyridine [1] has proven to be a highly reactive electrophile, allowing SNAr mediated arylations to proceed in the presence of a range of nucleophilic side chains including cysteine, tyrosine, and lysine under mild reaction conditions
Summary
Perfluoroheteroaromatic derivatives such as pentafluoropyridine [1], tetrafluoro-pyrimidine [2] and tetrafluoropyridazine [3] are highly useful building blocks for organic synthesis because, in principle, all fluorine atoms may be displaced by nucleophiles via regioselective, sequential nucleophilic aromatic substitution reactions (SNAr). Despite this it should be noted that recently Pentelute et al demonstrated an elegant route through which arylation at lysine could be achieved if a perfluorosulfone derivative of hexafluorobenzene is utilised.17 In comparison to 7, the more reactive pentafluoropyridine [1] was able to react with the lysine residues and the aromatic alcohol of the tyrosine residue under the same conditions (compounds 14 and 15, Table 2, entries 8 and 9 and ESI Fig. SI15, 16‡).
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
