Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 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.

PubMed Disclaimer

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.
See this image and copyright information in PMC

References

    1. Rosenblatt DH, Burrows EP. In: Supplement F: The Chemistry of Amino, Nitroso, and Nitro Compounds and Their Derivatives. Part 2. Patai S, editor. Wiley and Sons; Chichester: 1982. pp. 1085–1149.
    1. Field JD, Kropp PJ. J. Org. Chem. 2000;65:5937–5941. - PubMed
    2. Wittman MD, Halcomb RL, Danishefsky SJ. J. Org. Chem. 1990;55:1981–1983.
    1. Fennell KA, Miller MJ. J. Org. Chem. 1999;64:7451–7458.
    2. John ORS, Killeen NM, Knowles DA, Yau SC, Bagley MC, Tomkinson NCO. Org. Lett. 2007;9:4009–4012. - PubMed
    1. Bode JW, Fox RM, Baucom KD. Angew. Chem. Int. Ed. 2006;45:1248–1252. - PubMed
    1. Hackenberger CPR, Schwarzer D. Angew. Chem. Int. Ed. 2008;47:10030–10074. - PubMed

Publication types