American Chemical Society
jm960043j_si_001.pdf (1.33 MB)

Versatile Approach To Encoding Combinatorial Organic Syntheses Using Chemically Robust Secondary Amine Tags

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journal contribution
posted on 1996-04-12, 00:00 authored by Zhi-Jie Ni, Derek Maclean, Christopher P. Holmes, Martin M. Murphy, Beatrice Ruhland, Jeffrey W. Jacobs, Eric M. Gordon, Mark A. Gallop
Encoded combinatorial organic synthesis has recently emerged as a powerful tool for the discovery of biologically active compounds from complex chemical libraries. This report describes a new encoding methodology that uses chemically robust secondary amines as tags. These amines are incorporated into an N-[(dialkylcarbamoyl)methyl]glycine-coding oligomer through simple chemistry that is compatible with a wide range of polymer-supported transformations useful in combinatorial synthesis. In the decoding process acidic hydrolysis of the tagging polymer regenerates the secondary amines, which after dansylation are resolved and detected at sub-picomole levels by reversed-phase HPLC. The versatility of this strategy is demonstrated here by encoded syntheses of members of several representative heterocyclic compound classes, including β-lactams, 4-thiazolidinones, and pyrrolidines.