The Properties of Resin Supports and Their Effects on Solid­ Phase Organic Synthesis

Abstract

Solvated resin supports are important carriers for solid-phase organic synthesis in combinatorial chemistry and high-throughput parallel synthesis. The physical properties of resin, resin swelling and dynamic solvation, effects of solvated supports on synthesis, kinetics, site interaction, and product purity are reviewed. Selective solvation of resin alters the local reactivity and accessibility of the bound substrate and the mobility of the entrapped reagent. Resin solvation changes during the course of the reaction when the attached substrate changes its polarity or other physicochemical properties. Selective adsorption determines the reaction kinetics and the action of a phase-transfer catalyst further improves the reaction on resin. Sites interact with each other in 1% DVB polystyrene resins to varying degrees depending on solvent, resin, and reactivity of the pendant groups. Total site isolation seems only achievable by controlling several factors simultaneously such as lower loading and steric hindrance. Through the proper selection of resin and solvent, alternating solvents to accommodate dynamic solvation of the resin, optimization of kinetics when changing solid supports and a careful control of resin impurities, solid-phase organic synthesis can lead to high quality combinatorial libraries.