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Synthesis 2022; 54(16): 3558-3567
DOI: 10.1055/s-0041-1737411
DOI: 10.1055/s-0041-1737411
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Synthesis of Peptide N-Acylpyrroles via Anodically Generated N,O-Acetals
This work was supported by the Australian Research Council Centre of Excellence for Innovations in Peptide and Protein Science (CE200100012) and the Westpac Foundation (Research Fellowship to L.R.M.).
Abstract
An electrochemical approach to peptide C-terminal N-acylpyrroles is described from readily accessible C-terminal hydroxyproline-containing peptides, prepared via standard Fmoc solid-phase peptide synthesis (Fmoc-SPPS). Following electrochemical decarboxylation, the reactive hydroxyproline-derived N,O-acetal intermediate is aromatized under mild acidic conditions, which enable concomitant deprotection of amino acid side-chain protecting groups. The resulting peptide N-acylpyrrole is amenable to late-stage peptide modifications, including reduction with NaBH4 to deliver a valuable C-terminal peptide aldehyde motif.
Key words
decarboxylation - electrochemistry - anodic oxidation - aromatization - peptide N-acylpyrroles - late-stage modification - C-terminal modificationSupporting Information
- Supporting information for this article is available online at https://doi.org/10.1055/s-0041-1737411.
- Supporting Information
Publication History
Received: 21 January 2022
Accepted after revision: 23 February 2022
Article published online:
09 May 2022
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An earlier term, amidity, has also been used to quantify amide bond strength; see:
For selected examples, see:
To simplify the peptide synthesis, side-chain unprotected Hyp was incorporated and capping steps were omitted to avoid the formation of O-acetylated Hyp. The incorporation of Fmoc-Hyp(Ac)-OH was avoided due to the tendency of this amino acid to aggregate; see:
For selected examples, see:
For selected examples, see: