title: Diversity through a branched reaction pathway: generation of multicyclic scaffolds and identification of antimigratory agents.
abstract: A library of 91 heterocyclic compounds composed of 16 distinct scaffolds has been synthesized through a sequence of phosphine-catalyzed ring-forming reactions, Tebbe reactions, Diels-Alder reactions, and, in some cases, hydrolysis. This effort in diversity-oriented synthesis produced a collection of compounds that exhibited high levels of structural variation both in terms of stereochemistry and the range of scaffolds represented. A simple but powerful sequence of reactions thus led to a high-diversity library of relatively modest size with which to explore biologically relevant regions of chemical space. From this library, several molecules were identified that inhibit the migration and invasion of breast cancer cells and may serve as leads for the development of antimetastatic agents.
authors.affiliation: Department of Chemistry and Biochemistry, University of California, Los Angeles, 607 Charles E. Young Drive East, Los Angeles, CA 90095-1569, USA.
authors.forename: Zhiming
authors.initials: Z
authors.lastname: Wang
authors.forename: Sabrina
authors.initials: S
authors.lastname: Castellano
authors.forename: Sape S
authors.initials: SS
authors.lastname: Kinderman
authors.forename: Christian E
authors.initials: CE
authors.lastname: Argueta
authors.forename: Anwar B
authors.initials: AB
authors.lastname: Beshir
authors.forename: Gabriel
authors.initials: G
authors.lastname: Fenteany
authors.forename: Ohyun
authors.initials: O
authors.lastname: Kwon
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D002384:Catalysis; D020650:Combinatorial Chemistry Techniques; D003500:Cyclization; D005260:Female; D006571:Heterocyclic Compounds / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D006801:Humans; D015394:Molecular Structure; D010720:Phosphines / Q000737:chemistry
chemical_list: D000970:Antineoplastic Agents; D006571:Heterocyclic Compounds; D010720:Phosphines; C044646:phosphine