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ACS combinatorial science DOI:10.1021/co2000218

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

Publication TypeJournal Article
Year of Publication2011
AuthorsGerard, B, Duvall, JR, Lowe, JT, Murillo, T, Wei, J, Akella, LB, Marcaurelle, LA
JournalACS combinatorial science
Date Published2011/07/11

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).