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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.

SUBMITTER: Fitzgerald ME

PROVIDER: S-EPMC3289975 | biostudies-literature | 2012 Feb

REPOSITORIES: biostudies-literature

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Build/couple/pair strategy for the synthesis of stereochemically diverse macrolactams via head-to-tail cyclization.

Fitzgerald Mark E ME Mulrooney Carol A CA Duvall Jeremy R JR Wei Jingqiang J Suh Byung-Chul BC Akella Lakshmi B LB Vrcic Anita A Marcaurelle Lisa A LA

ACS combinatorial science 20120117 2

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 us ...[more]

PMID: 22252910

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