Ring opening of a resin-bound chiral aziridine with phenol nucleophiles.
An efficient and versatile solid-phase route for the preparation of aryl-alkyl ethers is described. Regioselective ring opening of a resin-bound chiral aziridine with phenolic nucleophiles constitutes the key feature of the present protocol that allows incorporation of fluorescent moieties and subsequent on-resin protecting group interconversion. Initial experiments demonstrated that a competing oligomerization may occur by concomitant attacks of transient nosylamide anions on neighboring aziridines, resulting in formation of dimeric and trimeric byproduct. Expectedly, the significance of this alternative reaction pathway was strongly dependent on resin loading, and a low loading (<0.4 mmol g(-1)) was required for obtaining high yields of the desired aryl-alkyl ethers. The developed methodology allowed preparation of novel N-Fmoc-protected coumaryl amino acid building blocks, which were incorporated into peptides by solid-phase peptide synthesis.
Ottesen
Lars K
LK
Department of Medicinal Chemistry, Faculty of Pharmaceutical Sciences, University of Copenhagen, Universitetsparken 2, DK-2100 Copenhagen, Denmark.
Jaroszewski
Jerzy W
JW
Franzyk
Henrik
H
D001388:Aziridines / Q000737:chemistry*; D002851:Chromatography, High Pressure Liquid; D003500:Cyclization; D005456:Fluorescent Dyes / Q000737:chemistry; D009682:Magnetic Resonance Spectroscopy; D010636:Phenols / Q000737:chemistry*; D013237:Stereoisomerism
D001388:Aziridines; D005456:Fluorescent Dyes; D010636:Phenols; C033132:aziridine