Solid-phase linkers

A class of photolabile linkers has been developed to circumvent the use of silyl ethers as linkers and allow for the use of temporary silyl protecting groups.34,35 Photolabile linkers, such as 2, often involve the use of o-nitrobenzyl ether groups. This functional group is stable to a variety of conditions however, cleavage from the polymer support is often slow and 

Cleavage Methods for Solid-Phase Oligosaccharide Synthesis 

More recently, linkers similar to 4, making use of alkene metathesis as the cleavage method, have been developed.37,38 Alkene-type linkers are stable to acidic and basic reaction conditions, and the double bond acts as a handle for the final cleavage event. This is an attractive option because the linker 

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Scheme 27. Synthesis of bis(pyrazol-l-yl)acetic acids with solid phase linkers (68).

Considering all these features and limitations, it is understandable that currently there is no general procedure available, such as the Fmoc or Boc protocols that are available for nonfunctionalized peptides. However, several approaches have been developed in the last two decades to make lipidated peptides accessible. This chapter describes both the corresponding solution-phase approaches and solid-support approaches for the synthesis of lipidated peptides. In line with the framework sketched above, both the different protecting groups and solid-phase linker systems that have been developed will be reviewed. 

In reviewing the chemical diversity systems outlined in the previous chapter, the utility of applying a variety of different reaction types productively on solid phase has become apparent. Combinatorial chemists must develop the skills to maintain a high level of flexibility, with respect to the pathways accessible in the solid-phase mode of operation. The diversity of building blocks, available in principle to everyone, needs to be complemented by a diversity of methods on how to link them. This skill base is available only to the advanced laboratories in the field. Furthermore, the know-how in the area of protecting group chemistry needs extension into the issues concerning solid phase linkers and the actual solid-phase matrices. 

FIGURE 6.1 Some commonly used solid-phase linkers and their cleavage conditions. 

Keywords Radicals Solid phase Linkers Supported reagents... 

Floreancig [42] has described a new solid-phase linker system cleaved by oxidative electron transfer. The cleavage process is based on the oxidative fragmentation of homobenzylic ethers. Acetal 230, immobilized on a soluble oligonorbornene scaffold prepared by ROMP polymerization, was efficiently... 

S.4 Cope elimination for the cleavage of solid-phase linkers... 

Figure 33 Use of enzyme-labile solid phase linker in the synthesis of tetrahydro-P-carbolines.

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