New linkers for solid phase synthesis 

Evaluation of a new linker system cleaved using samarium(II) iodide. Application in the solid phase synthesis of carbonyl compounds

Fiona McKerlie, Iain M. Rudkin, Graham Wynne and David J. Procter

A family of new linkers for use in solid phase organic synthesis has been reported by David Proctor and colleagues at the universities of Glasgow and Manchester. 

Solid phase organic synthesis has emerged as an invaluable tool for the preparation of collections of organic compounds.   The approach is based on the use of solid surfaces to facilitate the generation of a specific molecule.   Substrates are attached to solid supports via linker molecules, which upon completion of the reaction must be cleaved from the products.   A problem however lies in being able to remove the linker without damaging the products or leaving a piece of the linker, named a trace, attached.

The strategy of Proctor et al. was to construct a linker based on the mild, neutral reduction of alpha-heteroatom substituted carbonyl compounds using samarium iodide. Applying an oxygen substituted version of this linker to the solid phase synthesis of ketones and amides allowed the formation of the required products and their complete removal from the linker molecule.

The team are working to develop this new class of linkers for use in the synthesis of biologically important molecules, where the linker not only tethers the substrate to a polymer support but also plays a key role in the formation of the product. It is hoped that this technology can be used in combinatorial chemistry to provide large libraries of compounds for biological evaluation.