Native chemical ligation at a base-labile 4-mercaptobutyrate Nα-auxiliary

doi:10.1016/j.bmcl.2016.01.060

Bioorganic & Medicinal Chemistry Letters

Volume 26, Issue 5, 1 March 2016, Pages 1434-1437

https://doi.org/10.1016/j.bmcl.2016.01.060 Get rights and content

Abstract

Native chemical ligation (NCL) proceeds via a S–N acyl shift and, therefore, requires N-terminal cysteine. N^α-auxiliaries have long been used to enable NCL beyond cysteine. However, the reversibility of the S–N acyl shift under the acidic conditions used to remove the commonly applied N-benzyl auxiliaries limits the scope of this reaction. Herein, we introduce a new class of N^α-auxiliary which is designed for removal under mild basic conditions. The 3-N-linked 4-mercaptobutyrate auxiliary is readily synthesized in a single step and enables introduction on solid phase by means of reductive amination. The usefulness of the new auxiliary was demonstrated in the synthesis of the anti-microbial C-terminal domain of Dermicidine-1L.

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Acknowledgments

This work was financially supported by the Deutsche Forschungsgemeinschaft (Se819-15-1, SPP 1623). We acknowledge Luxembourg Bio Technologies Ltd for providing OxymaPure.

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Native chemical ligation at a base-labile 4-mercaptobutyrate Nα-auxiliary

Abstract

Graphical abstract

Section snippets

Acknowledgments

Curr. Opin. Chem. Biol.

Annu. Rev. Biochem.

Org. Lett.

Tetrahedron Lett.

J. Am. Chem. Soc.

Eur. J. Org. Chem.

Angew. Chem., Int. Ed.

Science

J. Am. Chem. Soc.

Biopolymers

J. Am. Chem. Soc.

Chem. Commun.

J. Am. Chem. Soc.

Angew. Chem., Int. Ed.

J. Am. Chem. Soc.

Angew. Chem., Int. Ed.

Angew. Chem., Int. Ed.

J. Am. Chem. Soc.

ChemBioChem

Native chemical ligation at a base-labile 4-mercaptobutyrate N^α-auxiliary