title: Build/couple/pair strategy for the synthesis of stereochemically diverse macrolactams via head-to-tail cyclization.
abstract: A build/couple/pair (B/C/P) strategy was employed to generate a library of 7936 stereochemically diverse 12-membered macrolactams. All 8 stereoisomers of a common linear amine precursor were elaborated to form the corresponding 8 stereoisomers of two regioisomeric macrocyclic scaffolds via head-to-tail cyclization. Subsequently, these 16 scaffolds were further diversified via capping of two amine functionalities on SynPhase Lanterns. Reagents used for solid-phase diversification were selected using a sparse matrix design strategy with the aim of maximizing coverage of chemical space while adhering to a preset range of physicochemical properties.
authors.affiliation: Chemical Biology Platform, Broad Institute of MIT and Harvard, Cambridge, Massachusetts 02142, United States.
authors.forename: Mark E
authors.initials: ME
authors.lastname: Fitzgerald
authors.forename: Carol A
authors.initials: CA
authors.lastname: Mulrooney
authors.forename: Jeremy R
authors.initials: JR
authors.lastname: Duvall
authors.forename: Jingqiang
authors.initials: J
authors.lastname: Wei
authors.forename: Byung-Chul
authors.initials: BC
authors.lastname: Suh
authors.forename: Lakshmi B
authors.initials: LB
authors.lastname: Akella
authors.forename: Anita
authors.initials: A
authors.lastname: Vrcic
authors.forename: Lisa A
authors.initials: LA
authors.lastname: Marcaurelle
mesh_terms: D003500:Cyclization; D047029:Lactams, Macrocyclic / Q000138:chemical synthesis* / Q000737:chemistry; D060327:Solid-Phase Synthesis Techniques / Q000379:methods; D013237:Stereoisomerism
chemical_list: D047029:Lactams, Macrocyclic