title: Synthesis of complex and diverse compounds through ring distortion of abietic acid.
abstract: Many compound screening collections are populated by members that possess a low degree of structural complexity. In an effort to generate compounds that are both complex and diverse, we have developed a strategy that uses natural products as a starting point for complex molecule synthesis. Herein we apply this complexity-to-diversity approach to abietic acid, an abundant natural product used commercially in paints, varnishes, and lacquers. From abietic acid we synthesize a collection of complex (as assessed by fraction of sp(3) -hybridized carbons and number of stereogenic centers) and diverse (as assessed by Tanimoto analysis) small molecules. The 84 compounds constructed herein, and those created through similar efforts, should find utility in a variety of biological screens.
authors.affiliation: Department of Chemistry, University of Illinois at Urbana-Champaign, 261 RAL, Box 36-5, 600 S. Mathews, Urbana, IL 61801 (USA).
authors.forename: Ryan J
authors.initials: RJ
authors.lastname: Rafferty
authors.forename: Robert W
authors.initials: RW
authors.lastname: Hicklin
authors.forename: Katherine A
authors.initials: KA
authors.lastname: Maloof
authors.forename: Paul J
authors.initials: PJ
authors.lastname: Hergenrother
mesh_terms: D045784:Abietanes / Q000138:chemical synthesis* / Q000737:chemistry*; D001688:Biological Products / Q000737:chemistry*; D015195:Drug Design; D005343:Fibrinolytic Agents / Q000138:chemical synthesis* / Q000737:chemistry*; D015394:Molecular Structure
chemical_list: D045784:Abietanes; D001688:Biological Products; D005343:Fibrinolytic Agents; C023710:abietic acid
keywords: abietic acid; high-throughput screening; molecular diversity; natural products; ring distortion