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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
Language(s) - English
Resource type - Journals
eISSN - 1521-3757
pISSN - 0044-8249
DOI - 10.1002/ange.201604652
Subject(s) - druggability , combinatorial chemistry , electrophile , chemistry , reagent , chemical space , drug discovery , negishi coupling , reactivity (psychology) , computer science , nanotechnology , materials science , organic chemistry , biochemistry , gene , catalysis , medicine , alternative medicine , pathology
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.