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 af dette arbejde

Kemisk Institut

7 Citationer (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.

Originalsprog	Engelsk
Tidsskrift	Chemistry - A European Journal
Vol/bind	23
Udgave nummer	56
Sider (fra-til)	13869–13874
Antal sider	6
ISSN	0947-6539
DOI	https://doi.org/10.1002/chem.201702900
Status	Udgivet - 9 okt. 2017

Adgang til dokumentet

10.1002/chem.201702900

Citationsformater

@article{4091c612065c4a9493ac9e42355e5e08,

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.",

keywords = "Click chemistry, Conformational analysis, Diversity oriented synthesis, Peptide heterocycles, Pictet-Spengler",

author = "Yuanyuan Wang and Anders Madsen and Frederik Diness and Morten Meldal",

year = "2017",

month = oct,

day = "9",

doi = "10.1002/chem.201702900",

language = "English",

volume = "23",

pages = "13869–13874",

journal = "Chemistry - A European Journal",

issn = "0947-6539",

publisher = "Wiley - V C H Verlag GmbH & Co. KGaA",

number = "56",

}

TY - JOUR

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

Adgang til dokumentet

Fingeraftryk

Citationsformater