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Synthesis of Complex Druglike Molecules by the Use of Highly Functionalized Bench‐Stable Organozinc Reagents
Author(s) -
Greshock Thomas J.,
Moore Keith P.,
McClain Ray T.,
Bellomo Ana,
Chung Cheol K.,
Dreher Spencer D.,
Kutchukian Peter S.,
Peng Zhengwei,
Davies Ian W.,
Vachal Petr,
Ellwart Mario,
Manolikakes Sophia M.,
Knochel Paul,
Nantermet Philippe G.
Publication year - 2016
Publication title -
angewandte chemie international edition
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.831
H-Index - 550
eISSN - 1521-3773
pISSN - 1433-7851
DOI - 10.1002/anie.201604652
Subject(s) - druggability , combinatorial chemistry , electrophile , reagent , chemistry , chemical space , drug discovery , computer science , negishi coupling , computational biology , organic chemistry , biology , biochemistry , gene , catalysis
The reactivity of a representative set of 17 organozinc pivalates with 18 polyfunctional druglike electrophiles (informers) in Negishi cross‐coupling reactions was evaluated by high‐throughput experimentation protocols. The high‐fidelity scaleup of successful reactions in parallel enabled the isolation of sufficient material for biological testing, thus demonstrating the high value of these new solid zinc reagents in a drug‐discovery setting and potentially for many other applications in chemistry. Principal component analysis (PCA) clearly defined the independent roles of the zincates and the informers toward druggable‐space coverage.