Traceless linkers, library synthesis using

Nowadays, solid-phase synthesis has been used as a powerful tool in organic chemistry, especially to prepare small molecule libraries. New linkers to obtain different functionalities after cleavage have been developed. There are different linkers strategies (Fig. 3.2), for example traceless linkers, multifunctional linkers, safety catch linkers, fragmentation/ cycloreversion cleavage linkers, cyclization cleavage linkers, which are useful methods for combinatorial solid-phase chemistry. 

The first traceless linkers for arenes were silyl linkers. This linker type was used in the synthesis of a benzodiazepine library, a milestone in the solid-phase synthesis of small organic molecules (Scheme 6.1.9). Synthesis of the linker involves lithium-halogen exchange and, after chlorosilane attachment, coupling with an... 

Different polyethylene glycol polymers were used in various papers and proved to be very reliable and useful for different classes of molecules their use for the synthesis of peptides [180, 181], of peptidomimetics [182] and of oligosaccharide libraries [183] was reported as the development and the use of a new PEG-linked traceless linker [184, 185], the selection of ligands for asymmetric Sharpless dihydroxylation [186-188], the use of PEG-linked triarylphosphines for LPCS requiring Mitsunobu or Staudinger conditions [189], the use of PEG-based supports to prepare a library of [l,4]oxazepine-7-ones [190] and the use of PEG-supported Schiff bases for the synthesis of a-substituted amino acids [191], Other examples of soluble polymers used for LPCS may include cellulose[192], polyacrylamide [193] polyvinyl alcohol [194, 195], various copolymers [196, 197] and NCPS [198-200]. Three excellent reviews [201-203] summarized the properties of PEG and other soluble polymers and their applications to the synthesis of peptides, oligonucleotides,... 

SCHEME 10.6 Strategy for the solid-phase synthesis of a trisaccharide library using a phenylsulfonate traceless linker. 

Takahashi, T. et al.. Synthesis of a trisaccharide library by using a phenylsulfonate traceless linker on Synphase Crowns, Angew. Chem., Int. Ed. Engl, 40, 3230, 2001. 

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