Solid-phase organic chemistry SPOC

Solid-phase organic chemistry (SPOC) has undergone a resurgence in recent years, largely brought on by its application to combinatorial chemistry. The solution-phase chemist has had for some time a number of excellent collections on available reactions. The solid-phase chemist has not had access to a similar comprehensive collection, although a few excellent reviews have been published (see the Reviews section). 

This review covers recent literature, and literature going back to the 1960s. It is intended as a resource for the chemist when planning a solid-phase synthesis. Through the references given, the chemist can gain an appreciation as to how a reaction may be performed on the solid phase. The conditions previously described may not be ideal for combinatorial chemistry. However, they may provide the chemist with a useful starting point. 

An important difference between solution-phase and solid-phase chemistry is the new variable the polymer support. The polymer has significant influence on the reaction. There have been many solid supports used over the years with variation in polymer type, degree of cross-linking, and even quality. These factors have significant influence on solvation properties and reaction kinetics, and hence on synthesis characteristics. Various grafted polymers may have characteristics that differ from other supports. Consequently, the optimal conditions for a reaction on one polymer may be different from those for the same reaction on a different polymer. This should not dishearten the chemist. A reported reaction may be used as the basis for optimization studies of the reaction on a different support. Variables such as solvent, temperature, and reaction time may all be investigated to optimize the reaction on the new surface. 

This compilation, although extensive, is not exhaustive. Apologies to any who find then-papers omitted Comments to improve the next edition are welcome. 

The following issues are devoted to combinatorial chemistry and contain some interesting SPOC reviews Acc. Chem. Res., 29 (3) (1996) Chemtracts-Org. Chem., 8 (1) (1995). For a historical perspective, see Merrifield s original paper Mer63. 

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P White. Combinatorial Chemistry Catalog Solid Phase Organic Chemistry (SPOC) Handbook. 2nd ed. Laufelfingen Calbiochem-Novabiochem, 1997. 

Such a procedure is well established in the case of peptides, but solid-phase organic chemistry (SPOC) is more difficult. Optimization of the chemistry is required prior to library generation most of the time. Compound identification is complicated by the insolubility of the support. Release of the anchored structure in solution followed by standard spectroscopic analyses may impart delay and/or affect product integrity (9). A direct monitoring of supported organic reactions is thus preferable to the cleave and analyze methodology. Nevertheless, it presents several constraints. A common resin bead loaded at 0.8 mmol/g commonly produces nanomole quantities of the desired compound, and only 1% of the molecules are located at the outer surface of the bead (10). Very few materials, covalently bound to the insoluble support, are thus available for the analysis, which should ideally be nondestructive. 

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