Combinatorial synthesis on macroscopic solid support units

The quality of our every day life is strongly affected by the new compounds and new materials introduced as a result of scientific research. In the last decade of the last century the traditional approach of research, that is, making and testing one new substance at a time, was replaced by the more efficient combinatorial methods. The philosophy staying behind these methods requires preparing a large array of compounds instead a single one. Two such methods are extensively used: the parallel synthesis and the split-mix procedure.In the parallel synthesis each compound is synthesized in a separate vessel. The number of operations used in the synthesis like the delivery of reagents and solvents is practically the same as in the conventional approach. The gain is in the reaction time. The time used for the synthesis of an array of 100 compounds essentially the same, as that needed for preparation of a single compound in the conventional approach.Following the split-mix procedure the gain is not only in the reaction time. The number of the reaction vessels in each reaction step is reduced to a minimum, that is, to the number of the executable reactions and, as a consequence, the number of operations needed in the synthesis is also substantially reduced. This explains the huge efficiency of the method. Although the split-mix synthesis leads to individual compounds, the quantity of the substance formed in a microscopic bead is very low. In order to overcome this problem while preserving the exceptionally high efficiency, the split-mix method was modified to use macroscopic solid support units instead of the microscopic beads. In one of the methods the resin was enclosed into a permeable capsule together with a transponder that carried the code of the capsule. Before each reaction step the capsules coming out from a reaction vessel were redistributed among the vessels of the next step according to their code. The other method, the string synthesis, used no label of any kind on the support units. The paper will compare the efficiency of redistribution in the two methods and describes a new version of string synthesis that makes possible to prepare selected parts of combinatorial libraries.