Synthesis of Complex Druglike Molecules by the Use of Highly Functionalized Bench‐Stable Organozinc Reagents. Issue 44 (30th September 2016)

• Record Type: Journal Article
• Authors: 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.
• Is Part Of: Angewandte Chemie international edition. Volume 55:Issue 44(2016)
• Page Start: 13714
• Page End: 13718
• Publication Date: 2016-09-30
• Subjects: druglike molecules -- high-throughput screening -- late-stage functionalization -- medicinal chemistry -- organozinc reagents; Chemistry -- Periodicals; 540
• DOI: 10.1002/anie.201604652
• Languages: English
• ISSNs: 1433-7851

Abstract

Abstract: 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. Abstract : A solid foundation for drug discovery : The reactivity of a set of 17 organozinc pivalates with 18 polyfunctional, druglike electrophiles (informers) in Negishi cross‐coupling reactions was evaluated by high‐throughput experimentation (see scheme). The high‐fidelity scaleup of successful reactions in parallel gave sufficient material for biological testing, thus demonstrating the high value of these solid zinc reagents in a drug‐discovery setting.