Semi-automated high throughput combinatorial solid-phase organic synthesis

A semi-automated technique for massive parallel solid-phase organic synthes is based on a "split only" strategy is described. Two different types of pu rpose-oriented reaction vessels are used. The initial steps are performed i n domino blocks, and the resin-bound intermediates then split into wells of a micro plate for the last combinatorial step. The domino block is a react ion block for manual and semi-automatic parallel solid-phase organic synthe sis that simplifies liquid exchange and integrates common synthetic steps. The synthesis in micro plates does not use any filter for separation of res in beads from the supernatant liquid, and allows high throughput parallel s ynthesis on solid phase to be performed. This technique, documented on exam ples of diverse disubstituted benzenes, includes the use of gaseous cleavag e in the last synthetic step and allows the synthesis of thousands of compo unds per day in mg quantities. (C) 1999 John Wiley & Sons, Inc.