Synthesis
DOI: 10.1055/a-1695-1095
paper

A Convenient On-Site Oxidation Strategy for the N-hydroxylation of Melanostatin Neuropeptide using Cope Elimination

1  Chemistry and Biochemistry, University of Porto Faculty of Sciences, Porto, Portugal (Ringgold ID: RIN131674)
,
Sara C. Silva-Reis
1  Chemistry and Biochemistry, University of Porto Faculty of Sciences, Porto, Portugal (Ringgold ID: RIN131674)
,
1  Chemistry and Biochemistry, University of Porto Faculty of Sciences, Porto, Portugal (Ringgold ID: RIN131674)
,
Xavier C. Correia
1  Chemistry and Biochemistry, University of Porto Faculty of Sciences, Porto, Portugal (Ringgold ID: RIN131674)
,
Hugo F. Costa-Almeida
1  Chemistry and Biochemistry, University of Porto Faculty of Sciences, Porto, Portugal (Ringgold ID: RIN131674)
› Author Affiliations
Supported by: Fundação para a Ciência e a Tecnologia 2020.02311.CEECIND/CP1596/CT0004,SFRH/BD/147463/2019,UIDB/50006/2020

In this work, a convenient synthetic protocol for the unprecedented N-hydroxylation of proline residue in Melanostatin (MIF-1) neuropeptide is reported. This methodology is grounded on the incorporation of N-(cyanoethyl)prolyl residue followed by on-site oxidation by Cope elimination with m-chloroperbenzoic acid, exploring the unrecognized dual role of the cyanoethyl group as an effective N-protecting group under peptide synthesis conditions and as a suitable leaving group during the chemoselective on-site N-oxidation. Following this protocol N-hydroxy-MIF-1 is obtained with 78% global yield from N-(cyanoethyl)-L-proline. This synthetic approach opens a new avenue for access to N-hydroxylated Melanostatin analogs with direct application in neurochemistry and Parkinson’s research.



Publication History

Received: 26 October 2021

Accepted after revision: 11 November 2021

Publication Date:
11 November 2021 (online)

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