Solid-phase synthesis multiple reaction systems

The repetitive nature of oligomeric synthesis has enabled the rapid implementation of solid-phase and automated methods for DNA [20,21,85,86] and peptide combinatorial libraries. Using these systems for the synthesis of single compounds or mixtures of compounds, multiple reaction vessels numbering 8 [45], 15 [80], 20 [59], 24 [50], 25 [57,58], 36 [53-55,77-79], 48 [26,39-41], or 96 [42-44] can be manipulated. Only a few of these systems enable automated resin mixing and splitting within the instrument to generate mixtures of compounds [53,59,78,87,88],... 

An automated solid-phase instrument requires systems to deliver the reagents, solvents, and activated monomers to the reaction vessel. The size and number of the reagent reservoirs are dependent on the chemistry, sequence, and scale of synthesis. The capacity of the reagents and solvent reservoirs should be sufficient to accommodate the desired scale range and multiple syntheses without refilling. The number of reagent reservoirs should be greater than required for the standard chemistries to allow the flexibility to perform specialized reactions. 

As these reagent systems are anchored on a solid, they also allow the simultaneous use of multiple reagents to achieve one-pot transformations where, because of incompatibility of the reagents, no solution-phase equivalent exists or would require intermediate isolation. Many examples of this are illustrated in the following sections where it can be seen that these concepts add a new dimension to how one can think about organic synthesis and will certainly have important ramifications on the design and implementation of new chemical reactions and processes in the future. 

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