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

• Published in: Journal of medicinal chemistry Vol. 39; no. 8; pp. 1601 - 1608
• Main Authors: Ni, Zhi-Jie, Maclean, Derek, Holmes, Christopher P, Murphy, Martin M, Ruhland, Beatrice, Jacobs, Jeffrey W, Gordon, Eric M, Gallop, Mark A
• Format: Journal Article
• Language: English
• Published: WASHINGTON American Chemical Society 12.04.1996; Amer Chemical Soc
• Subjects: Anti-Bacterial Agents - chemical synthesis; Biological and medical sciences; Chemistry; Chemistry, Medicinal; Exact sciences and technology; General pharmacology; Lactams; Life Sciences & Biomedicine; Medical sciences; Organic chemistry; Pharmacology & Pharmacy; Pharmacology. Drug treatments; Physicochemical properties. Structure-activity relationships; Pyrrolidines - chemical synthesis; Science & Technology; Thiazoles - chemical synthesis; LIBRARIES; Sulfur nitrogen heterocycle; Automation; Five membered ring; Four membered ring; Nitrogen heterocycle; Lactam; Pyrrolidine derivatives; α-Aminoacid; Combinatorial method; Tagging; Carboxamide; Solid phase; Chemical synthesis; Secondary amine
• ISSN: 0022-2623; 1520-4804
• DOI: 10.1021/jm960043j

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.