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DOI: 10.1055/s-0037-1611635
Synthesis and Evaluation of Cyclic Acetals of Serine Hydroxylamine for Amide-Forming KAHA Ligations
This work was supported by the Swiss National Science Foundation (169451).Publication History
Received: 21 November 2018
Accepted: 27 November 2018
Publication Date:
07 January 2019 (online)
Abstract
The α-ketoacid–hydroxylamine (KAHA) ligation allows the coupling of unprotected peptide segments. The most widely used variant employs a 5-membered cyclic hydroxylamine that forms a homoserine ester as the primary ligation product. While very effective, monomers that give canonical amino acid residues are in high demand. In order to preserve the stability and reactivity of cyclic hydroxylamines, but form a canonical amino acid residue upon ligation, we sought to prepare cyclic derivatives of serine hydroxylamine. An evaluation of several cyclization strategies led to cyclobutanone ketals as the leading structures. The preparation, stability, and amide-forming ligation of these serine-derived ketals are described.
Supporting Information
- Supporting information for this article is available online at https://doi.org/10.1055/s-0037-1611635.
- Supporting Information
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Other amide-forming ligations include the traceless Staudinger and the serine/threonine ligation: