Purification of combinatorial libraries

Harold N. Weller
Bristol-Myers Squibb Pharmaceutical Research Institute, P.O. Box 4000, Princeton, NJ 08543, U.S.A.

Abstract
In the early days of combinatorial chemistry, much attention focused on preparation of large libraries for lead discovery. Recently, though, the focus has shifted toward smaller, more focused libraries for lead optimization. These focused libraries generally consist of individual discrete compounds. Biological assay requirements often require compounds of high purity, thus development of automated high throughput purification methods has received new attention in the past several years. This paper covers automated high throughput purification methods that have been applied to libraries of discrete compounds. Literature published through February 1998 is included. Purification methods discussed include extraction methods, scavenger methods, solid phase extraction, and preparative HPLC.

Keywords
chromatography, HPLC, library, purification, SPE