title: Versatile approach to encoding combinatorial organic syntheses using chemically robust secondary amine tags.
abstract: 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 beta-lactams, 4-thiazolidinones, and pyrrolidines.
authors.affiliation: Affymax Research Institute, Palo Alto, California 94304, USA.
authors.forename: Z J
authors.initials: ZJ
authors.lastname: Ni
authors.forename: D
authors.initials: D
authors.lastname: Maclean
authors.forename: C P
authors.initials: CP
authors.lastname: Holmes
authors.forename: M M
authors.initials: MM
authors.lastname: Murphy
authors.forename: B
authors.initials: B
authors.lastname: Ruhland
authors.forename: J W
authors.initials: JW
authors.lastname: Jacobs
authors.forename: E M
authors.initials: EM
authors.lastname: Gordon
authors.forename: M A
authors.initials: MA
authors.lastname: Gallop
mesh_terms: D000900:Anti-Bacterial Agents / Q000138:chemical synthesis*; D007769:Lactams; D011759:Pyrrolidines / Q000138:chemical synthesis*; D013844:Thiazoles / Q000138:chemical synthesis*
chemical_list: D000900:Anti-Bacterial Agents; D007769:Lactams; D011759:Pyrrolidines; D013844:Thiazoles