A multifunctional catalyst that stereoselectively assembles prodrugs

• DOI: 10.1126/science.aam7936
• Publication Date: 2017-04-27T17:55:54Z
• Authors: Daniel A. DiRocco; Yining Ji; Edward C. Sherer; Artis Klapars; Mikhail Reibarkh; James Dropinski; Rose Mathew; Peter Maligres; Alan M. Hyde; John Limanto; Andrew Brunskill; Rebecca T. Ruck; Louis-Charles Cam...; Ian W. Davies
• Keywords: Rational design; Nucleoside analogue

Getting phosphorus into healthy shape ProTide therapeutics play a trick on the body, getting nucleoside analogs where they need to be by decorating them with unnatural phosphoramidates in place of ordinary phosphates. These compounds pose an unusual synthetic challenge because their configuration must controlled at phosphorus; most methods have been refined manipulate geometry carbon. DiRocco et al. report metal-free, small-molecule catalyst that attains high selectivity for phosphoramidation activating both reaction partners. Kinetic studies early prototype revealed double role inspired rational design more active and selective dimeric structure. Science , this issue p. 426