Diversity-Oriented Syntheses by Combining CuAAC and Stereoselective INCIC Reactions with Peptides

Yuanyuan Wang; Anders Madsen; Frederik Diness; Morten Meldal

doi:10.1002/chem.201702900

Diversity-Oriented Syntheses by Combining CuAAC and Stereoselective INCIC Reactions with Peptides

Yuanyuan Wang, Anders Madsen, Frederik Diness^*, Morten Meldal

^*Corresponding author for this work

Department of Chemistry

7 Citations (Scopus)

Abstract

Cascade reactions proceeding through peptide-derived N-carbamoyl iminium ions are reported. Two new reactions of N-carbamoyl iminium ions are described, including a stereoselective double cyclization generating N,N′-aminals and an acid-promoted auto-oxidation. Mechanistic investigations revealed that the N,N′-aminal formation is reversible under strongly acidic conditions. Both of these new reactions proved to be completely orthogonal to subsequent CuAAC chemistry. The reactions were performed in solution and on solid support. The robustness and high stereoselectivity of the methodology holds great promise for applications in parallel diversity-oriented synthesis and in combinatorial synthesis for drug screening.

Original language	English
Journal	Chemistry - A European Journal
Volume	23
Issue number	56
Pages (from-to)	13869–13874
Number of pages	6
ISSN	0947-6539
DOIs	https://doi.org/10.1002/chem.201702900
Publication status	Published - 9 Oct 2017

Keywords

Click chemistry
Conformational analysis
Diversity oriented synthesis
Peptide heterocycles
Pictet-Spengler

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title = "Diversity-Oriented Syntheses by Combining CuAAC and Stereoselective INCIC Reactions with Peptides",

abstract = "Cascade reactions proceeding through peptide-derived N-carbamoyl iminium ions are reported. Two new reactions of N-carbamoyl iminium ions are described, including a stereoselective double cyclization generating N,N′-aminals and an acid-promoted auto-oxidation. Mechanistic investigations revealed that the N,N′-aminal formation is reversible under strongly acidic conditions. Both of these new reactions proved to be completely orthogonal to subsequent CuAAC chemistry. The reactions were performed in solution and on solid support. The robustness and high stereoselectivity of the methodology holds great promise for applications in parallel diversity-oriented synthesis and in combinatorial synthesis for drug screening.",

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T1 - Diversity-Oriented Syntheses by Combining CuAAC and Stereoselective INCIC Reactions with Peptides

AU - Wang, Yuanyuan

AU - Madsen, Anders

AU - Diness, Frederik

AU - Meldal, Morten

PY - 2017/10/9

Y1 - 2017/10/9

N2 - Cascade reactions proceeding through peptide-derived N-carbamoyl iminium ions are reported. Two new reactions of N-carbamoyl iminium ions are described, including a stereoselective double cyclization generating N,N′-aminals and an acid-promoted auto-oxidation. Mechanistic investigations revealed that the N,N′-aminal formation is reversible under strongly acidic conditions. Both of these new reactions proved to be completely orthogonal to subsequent CuAAC chemistry. The reactions were performed in solution and on solid support. The robustness and high stereoselectivity of the methodology holds great promise for applications in parallel diversity-oriented synthesis and in combinatorial synthesis for drug screening.

AB - Cascade reactions proceeding through peptide-derived N-carbamoyl iminium ions are reported. Two new reactions of N-carbamoyl iminium ions are described, including a stereoselective double cyclization generating N,N′-aminals and an acid-promoted auto-oxidation. Mechanistic investigations revealed that the N,N′-aminal formation is reversible under strongly acidic conditions. Both of these new reactions proved to be completely orthogonal to subsequent CuAAC chemistry. The reactions were performed in solution and on solid support. The robustness and high stereoselectivity of the methodology holds great promise for applications in parallel diversity-oriented synthesis and in combinatorial synthesis for drug screening.

KW - Click chemistry

KW - Conformational analysis

KW - Diversity oriented synthesis

KW - Peptide heterocycles

KW - Pictet-Spengler

U2 - 10.1002/chem.201702900

DO - 10.1002/chem.201702900

M3 - Journal article

C2 - 28833706

AN - SCOPUS:85029307123

SN - 0947-6539

VL - 23

SP - 13869

EP - 13874

JO - Chemistry: A European Journal

JF - Chemistry: A European Journal

IS - 56

ER -

Diversity-Oriented Syntheses by Combining CuAAC and Stereoselective INCIC Reactions with Peptides

Abstract

Keywords

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