ABSTRACT
It is truly interesting to follow the undulating development of the field of smallmolecule solid-phase organic synthesis (SPOS) since the seminal work of Leznoff in the early 1970s (1). It has traversed the gamut of intellectual scrutiny as being “ innovative,” “ esoteric,” and, more recently, “ powerful” with its application in high throughput synthesis (HTPS). In fact, from 1994 to 1998 the pharmaceuti cal and agrochemical industries were polarized toward the use of SPOS for the rapid preparation of diverse molecular libraries. This led to the development of start-up companies whose synthetic strategies (e.g., Affymax) or equipment line (e.g., Irori) were based primarily or exclusively on SPOS. More recently, the pendulum has again swung with respect to SPOS, only this time the movement is not necessarily away from it. Rather, solution-phase synthesis is being used increasingly to prepare molecular libraries because of adaptations of SPOS to facilitate reactions in the solution phase.
