Target molecule, structural assessment

When the target molecule is similar to known structures, or when a sound synthetic scheme is drawn, the assessment of the best experimental conditions in solution is straightforward, while the transfer of a reaction sequence onto SP requires more theoretical (selection of the best support and linker) and experimental work to find appropriate reaction conditions. 

This approach suffers from problems related to the influence of the support on reaction chemistries and the optimization of solid-supported chemistries, which may have completely different kinetics from their solution-phase analogues. Difficulties exist in assessing product purity or structure of compounds in the solid phase, often leading to expensive spectroscopic solutions. Working in the solid phase also limits the range of chemistry, which can be applied to a synthetic problem, not least because many solid phase approaches are so dependent upon amide bond formation. A further issue arises from the need for the perfect linker uncleaved in normal reaction conditions but perfectly cleaved when desired, preferably without a footprint in the target molecule. 

Fauman EB, Rai BK, Huang ES (2011) Structure-based druggability assessment-identifying suitable targets for small molecule therapeutics. Curr Opin Chem Biol 15 463 68... 

---