title: Application of a catalytic asymmetric Povarov reaction using chiral ureas to the synthesis of a tetrahydroquinoline library.
abstract: A 2328-membered library of 2,3,4-trisubstituted tetrahydroquinolines was produced using a combination of solution- and solid-phase synthesis techniques. A tetrahydroquinoline (THQ) scaffold was prepared via an asymmetric Povarov reaction using cooperative catalysis to generate three contiguous stereogenic centers. A matrix of 4 stereoisomers of the THQ scaffold was prepared to enable the development of stereo/structure-activity relationships (SSAR) upon biological testing. A sparse matrix design strategy was employed to select library members to be synthesized with the goal of generating a diverse collection of tetrahydroquinolines with physicochemical properties suitable for downstream discovery.
authors.affiliation: Chemical Biology Platform, The Broad Institute of Harvard and MIT , 7 Cambridge Center, Cambridge, Massachusetts 02142, United States.
authors.forename: Baudouin
authors.initials: B
authors.lastname: Gerard
authors.forename: Morgan Welzel
authors.initials: MW
authors.lastname: O'Shea
authors.forename: Etienne
authors.initials: E
authors.lastname: Donckele
authors.forename: Sarathy
authors.initials: S
authors.lastname: Kesavan
authors.forename: Lakshmi B
authors.initials: LB
authors.lastname: Akella
authors.forename: Hao
authors.initials: H
authors.lastname: Xu
authors.forename: Eric N
authors.initials: EN
authors.lastname: Jacobsen
authors.forename: Lisa A
authors.initials: LA
authors.lastname: Marcaurelle
mesh_terms: D002384:Catalysis; D005240:Feasibility Studies; D015363:Quinolones / Q000737:chemistry*; D013237:Stereoisomerism; D013329:Structure-Activity Relationship; D014508:Urea / Q000737:chemistry*
chemical_list: D015363:Quinolones; D014508:Urea