Combinatorial Chemistry Review

Traceless Linkers

In some case, the starting materials are loaded onto the resin in one form, such as carboxylic acid, and cleaved in another form; a carboxamide for example. This is perfectly acceptable if the target compound requires the released function. (Peptides invariably contain a carboxylic acid or carboxamide.) However, the growth in interest in combinatorial libraries of low molecular weight non-peptides has elicited a need in new types of linker. These linkers show non-specific function after cleavage. Traceless linkers are so called because an examination of the final compound reveals no trace of the point of linkage to the solid phase.

Structure of Veber silyl traceless linker

The first and most widely explored of this traceless linker is the silyl linker. Silicon attached to a phenyl group can undergo a protodesilylation reaction cleaving the silicon aryl bond when treated with acid.