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. 2009 Mar 25;131(11):3864-5.
doi: 10.1021/ja900601c.

A reagent for the convenient, solid-phase synthesis of N-terminal peptide hydroxylamines for chemoselective ligations

Takeo Fukuzumi  1 , Jeffrey W Bode
Affiliations

A reagent for the convenient, solid-phase synthesis of N-terminal peptide hydroxylamines for chemoselective ligations

Takeo Fukuzumi et al. J Am Chem Soc. .

Abstract

A new N-sulfonyloxaziridine reagent for the conversion of N-terminal peptide amines to the corresponding hydroxylamines without overoxidation or erosion of stereochemistry is described. The products are N-terminal hydroxylamines, which are substrates for chemoselective amide-bond forming reactions with alpha-ketoacids. The success of this reagent arises from covalent precomplexation with the substrate via imine bond formation followed by an intramolecular oxygen-atom transfer to the amine. An unexpected stereochemical mismatch between the racemic reagent and the chiral peptide substrates was addressed by the preparation of an enantipure version of this reagent and provides further support for the proposed mechanism.

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Figures

Scheme 1
Scheme 1
Preparation of N-terminal peptide hydroxylamines with sulfonyloxaziridine reagent 1.
Scheme 2
Scheme 2
Synthesis of (±)–1.
Scheme 3
Scheme 3
Selective oxidation of tripeptide model 7 with 1.
Figure 1
Figure 1
Postulated directed oxidation of amines by 1.
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