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Synthesis of Structurally Diverse N‐Substituted Quaternary‐Carbon‐Containing Small Molecules from α,α‐Disubstituted Propargyl Amino Esters
Author(s) -
Mateu Natalia,
Kidd Sarah L.,
Kalash Leen,
Sore Hannah F.,
Madin Andrew,
Bender Andreas,
Spring David R.
Publication year - 2018
Publication title -
chemistry – a european journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.687
H-Index - 242
eISSN - 1521-3765
pISSN - 0947-6539
DOI - 10.1002/chem.201803143
Subject(s) - stereocenter , small molecule , combinatorial chemistry , propargyl , steric effects , drug discovery , molecule , chemistry , stereoselectivity , scaffold , stereochemistry , computational biology , nanotechnology , enantioselective synthesis , biology , organic chemistry , materials science , computer science , biochemistry , catalysis , database
Abstract N‐containing quaternary stereocenters represent important motifs in medicinal chemistry. However, due to their inherently sterically hindered nature, they remain underrepresented in small molecule screening collections. As such, the development of synthetic routes to generate small molecules that incorporate this particular feature are highly desirable. Herein, we describe the diversity‐oriented synthesis (DOS) of a diverse collection of structurally distinct small molecules featuring this three‐dimensional (3D) motif. The subsequent derivatisation and the stereoselective synthesis exemplified the versatility of this strategy for drug discovery and library enrichment. Chemoinformatic analysis revealed the enhanced sp 3 character of the target library and demonstrated that it represents an attractive collection of biologically diverse small molecules with high scaffold diversity.