Efficient loading of primary alcohols onto a solid phase using a trityl bromide linker

TY - JOUR

T1 - Efficient loading of primary alcohols onto a solid phase using a trityl bromide linker

AU - Crestey, François

AU - Ottesen, Lars Korsgaard

AU - Jaroszewski, Jerzy Witold

AU - Franzyk, Henrik

PY - 2008

Y1 - 2008

N2 - The Letter describes an improved, rapid and mild strategy for the loading of primary alcohols onto a polystyrene trityl resin via a highly reactive trityl bromide linker. This protocol facilitates an efficient resin loading even of acid-sensitive or heat-labile alcohols, which otherwise require expensive or non-commercial resin types. Secondary alcohols were only attached in moderate to low yields, while attempts to load a tertiary alcohol expectedly failed. Importantly, selective attachment of diols via a primary alcohol group in the presence of more hindered alcohol groups proved possible. The effects of activation time and reagent excess as well as alcohol structure were investigated. This improved method provides a convenient access to O-linked resin-bound N-Fmoc-protected amino alcohols that may be employed in SPS of peptides with C-terminal alcohol functionalities. In the case of a sensitive alcohol containing an activated aziridine functionality, the use of the trityl bromide linker proved superior to a recently described silver triflate-assisted trityl chloride resin-based procedure.

AB - The Letter describes an improved, rapid and mild strategy for the loading of primary alcohols onto a polystyrene trityl resin via a highly reactive trityl bromide linker. This protocol facilitates an efficient resin loading even of acid-sensitive or heat-labile alcohols, which otherwise require expensive or non-commercial resin types. Secondary alcohols were only attached in moderate to low yields, while attempts to load a tertiary alcohol expectedly failed. Importantly, selective attachment of diols via a primary alcohol group in the presence of more hindered alcohol groups proved possible. The effects of activation time and reagent excess as well as alcohol structure were investigated. This improved method provides a convenient access to O-linked resin-bound N-Fmoc-protected amino alcohols that may be employed in SPS of peptides with C-terminal alcohol functionalities. In the case of a sensitive alcohol containing an activated aziridine functionality, the use of the trityl bromide linker proved superior to a recently described silver triflate-assisted trityl chloride resin-based procedure.

KW - Former Faculty of Pharmaceutical Sciences

U2 - 10.1016/j.tetlet.2008.07.130

DO - 10.1016/j.tetlet.2008.07.130

M3 - Journal article

SN - 0040-4039

VL - 49

SP - 5890

EP - 5893

JO - Tetrahedron Letters

JF - Tetrahedron Letters

IS - 41

ER -