3.1 Resins For the preparation of m

3.1 Resins For the preparation of more than 50 umol of peptide, synthesis is normally carried out on beaded resins. Two practical procedures are in common usage,known as batchwise and continuous-flow, which differ principally in the method employed for washing of the resin between synthetic steps (Figure 4). In the batchwise process, the peptidyl resin is contained within a fritted reaction vessel, and reagents are added portionwise through the top of the vessel and removed by the appropriate application of positive nitrogen pressure or vacuum (Chapter 13, Section 2). In continuous-flow synthesis, the resin is packed into a column and washing is achieved by pumping solvent through the resin bed (see Chapter 13, Section 3). For batchwise synthesis, the base matrix used is almost invariably 1% divinylbenzene cross-linked polystyrene (PS). It is relatively inexpensive to produce, swells in the solvents most commonly used in peptide synthesis, namely DCM, DMF, and NMP, and can be readily functionalized using the Friedel-Crafts reaction with chloromethyl, aminomethyl, and benzhydrylamino groups. Polystyrene-based resins can also be used in continuous-flow synthesis, provided the beads are co-packed with glass beads and/or low flow rates are used. However, this arrangement is not entirely satisfactory, and the use of one of the supports especially manufactured for this purpose is preferred as they are designed to withstand the pressures generated in pumped-flow systems. The first commercially available continuous-flow supports consisted of a dimethylacrylamide carrier polymer contained within the pores of a rigid kieselguhr (Macrosorb®, NovaSyn K®) or polystyrene (Polyhipe®) matrix. These materials were somewhat friable and had a tendency to degrade over the course of long assemblies. Furthermore, being prepared from irregularshaped particles, the beads did not always pack evenly, which led to problems