Solid phase synthesis is widely used mainly because it is simple to operate compared with traditional technology. Reactions for solid-phase synthesis can be completed in three steps: reagent addition, filtration, and resin washing, which enables the development of numerous simple automated procedures. In solid-phase synthesis, standard, inexpensive, readily available equipment is typically utilized to perform a range of synthetic manipulations. For each step of the multi-step synthesis, the only purification required is the resin washing, and only the final product of the cleavage needs to be purified. In addition, in solid phase synthesis, high concentrations of reagents can be used to drive the reaction to completion.
Resins for solid-phase organic synthesis are insoluble supports with gel-type structures that readily allow penetration of reagents and solvents into the beads to sites where chemistry is taking place. Typical resins used for solid-phase synthesis consist of polystyrene cross-linked with 1-2% divinylbenzene (DVB). Three predominant polystyrene supports are chloromethyl polystyrene resins, which are widely employed for ether-based linker attachment, aminomethyl polystyrene resins (Merrifield resins), which allow a multitude of spacers/ linkers to be appended to the resin by amide bonds with stability under strongly acidic conditions, and hydroxymethyl polystyrene resins, which are ideal for the attachment of acids by esterification.
Solid phase synthesis requires a covalent linker group to attach the small molecule onto the polymeric resin. The selection of supports and linkers, as well as the evaluation of the proposed site of attachment to the target molecules are key to the development of solid phase synthesis. The physicochemical compatibility between resins, linkers, and reagents is a strong determining factor for successful solid-phase routes. The linkers bear many similarities to protecting groups in solution phase synthesis, requiring stability under reaction conditions yet selective cleavage upon synthesis completion to release products into solution. Additional desirable properties of a linker include reusability, reaction monitoring capability, sequential/partial release, and asymmetric induction.
A major limitation of solid-phase chemistry is the restricted commercial availability of specialized supports. Amerigo Scientific offers a wide range of solid-phase synthesis resins featuring hydroxyl, halogen, amino, and carboxyl functionalities, as well as a variety of specialized linkers to meet the various needs of solid phase synthesis.
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