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Synthesis of a stereochemically diverse library of medium-sized lactams and sultams via S(N)Ar cycloetherification.

ABSTRACT: We have implemented an aldol-based "build/couple/pair" (B/C/P) strategy for the synthesis of stereochemically diverse 8-membered lactam and sultam scaffolds via S(N)Ar cycloetherification. Each scaffold contains two handles, an amine and aryl bromide, for solid-phase diversification via N-capping and Pd-mediated cross coupling. A sparse matrix design strategy that achieves the dual objective of controlling physicochemical properties and selecting diverse library members was implemented. The production of two 8000-membered libraries is discussed including a full analysis of library purity and property distribution. Library diversity was evaluated in comparison to the Molecular Library Small Molecule Repository (MLSMR) through the use of a multifusion similarity (MFS) map and principal component analysis (PCA).

SUBMITTER: Gerard B

PROVIDER: S-EPMC3134123 | biostudies-literature | 2011 Jul

REPOSITORIES: biostudies-literature

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Synthesis of a stereochemically diverse library of medium-sized lactams and sultams via S(N)Ar cycloetherification.

Gerard Baudouin B Duvall Jeremy R JR Lowe Jason T JT Murillo Tiffanie T Wei Jingqiang J Akella Lakshmi B LB Marcaurelle Lisa A LA

ACS combinatorial science 20110428 4

We have implemented an aldol-based "build/couple/pair" (B/C/P) strategy for the synthesis of stereochemically diverse 8-membered lactam and sultam scaffolds via S(N)Ar cycloetherification. Each scaffold contains two handles, an amine and aryl bromide, for solid-phase diversification via N-capping and Pd-mediated cross coupling. A sparse matrix design strategy that achieves the dual objective of controlling physicochemical properties and selecting diverse library members was implemented. The prod ...[more]

PMID: 21526820

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