Synthesis of Complex Druglike Molecules by the Use of Highly Functionalized Bench‐Stable Organozinc Reagents. (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. Volume 128:Number 44(2016)
• Page Start: 13918
• Page End: 13922
• Publication Date: 2016-09-30
• Subjects: Hochdurchsatz-Screening -- Medizinische Chemie -- Organozinkreagentien -- Späte Funktionalisierung -- Wirkstoffartige Moleküle; Chemistry -- Periodicals; 540
• DOI: 10.1002/ange.201604652
• Languages: English
• ISSNs: 0044-8249

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.