A multifunctional catalyst that stereoselectively assembles prodrugs
2017; American Association for the Advancement of Science; Volume: 356; Issue: 6336 Linguagem: Inglês
10.1126/science.aam7936
ISSN1095-9203
AutoresDaniel A. DiRocco, Yining Ji, Edward C. Sherer, Artis Klapars, Mikhail Reibarkh, James F. Dropinski, Rose Mathew, Peter E. Maligres, Alan M. Hyde, John Limanto, Andrew P. J. Brunskill, Rebecca T. Ruck, Louis‐Charles Campeau, Ian W. Davies,
Tópico(s)Click Chemistry and Applications
ResumoGetting 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 be controlled at phosphorus; most methods have been refined to manipulate the geometry of carbon. DiRocco et al. report a metal-free, small-molecule catalyst that attains high selectivity for nucleoside phosphoramidation by activating both reaction partners. Kinetic studies with an early prototype revealed a double role for the catalyst that inspired the rational design of a more active and selective dimeric structure. Science , this issue p. 426
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