Ring opening of a resin-bound chiral aziridine with phenol nucleophiles

TY - JOUR

T1 - Ring opening of a resin-bound chiral aziridine with phenol nucleophiles

AU - Ottesen, Lars Korsgaard

AU - Jaroszewski, Jerzy W

AU - Franzyk, Henrik

PY - 2010/8/6

Y1 - 2010/8/6

N2 - (Figure presented) 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.

AB - (Figure presented) 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.

KW - Former Faculty of Pharmaceutical Sciences

U2 - 10.1021/jo100505c

DO - 10.1021/jo100505c

M3 - Journal article

C2 - 20617832

SN - 0022-3263

VL - 75

SP - 4983

EP - 4991

JO - Journal of Organic Chemistry

JF - Journal of Organic Chemistry

IS - 15

ER -