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