Details

Autor(en) / Beteiligte

• Gerard, Baudouin
• Duvall, Jeremy R
• Lowe, Jason T
• Murillo, Tiffanie
• Wei, Jingqiang
• Akella, Lakshmi B
• Marcaurelle, Lisa A

Titel

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

Ist Teil von

• ACS combinatorial science, 2011-07, Vol.13 (4), p.365-374

Ort / Verlag

United States

Erscheinungsjahr

2011

Quelle

MEDLINE

Beschreibungen/Notizen

• 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).