Synthesis 2022; 54(08): 2031-2036
DOI: 10.1055/a-1695-1095
paper

A Convenient On-Site Oxidation Strategy for the N-Hydroxylation of Melanostatin Neuropeptide Using Cope Elimination

,
Sara C. Silva-Reis
,
,
Xavier Cruz Correia
,
Hugo F. Costa-Almeida
This research was funded by Fundação para a Ciência e a Tecnologia (FCT, Portugal), through grants UIDB/50006/2020 (to LAQV-REQUIMTE Research Unit). S.C.S.-R. and I.E.S.-D. thank FCT for the Ph.D. grant with reference SFRH/BD/147463/2019 and the Scientific Employment Stimulus contract 2020.02311.CEECIND/CP1596/CT0004, respectively.


Abstract

Abstract

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 in 78% global yield from N-(cyanoethyl)-l-proline. This synthetic approach opens a new avenue for access to N-hydroxylated Melanostatin analogues with direct application in neurochemistry and Parkinson’s research.

Supporting Information



Publikationsverlauf

Eingereicht: 26. Oktober 2021

Angenommen nach Revision: 11. November 2021

Publikationsdatum:
11. November 2021 (online)

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