Whipping phosphorus into chiral shape

Abstract

Carbon isn’t the only type of chiral center found in organic compounds. Phosphorus can be chiral too. Many catalytic synthetic techniques do a great job at making carbon chiral centers. Comparable catalytic methods that synthesize chiral phosphates and phosphoramidates (phosphates with an NR2 instead of OH group) and do so with high stereoselectivity have been largely missing. But Daniel A. DiRocco and coworkers at Merck & Co. have now developed one (Science 2017, DOI: 10.1126/science.aam7936). The method could ease access to nucleoside phosphoramidates, also called pronucleotides—prodrugs with chiral phosphorus centers. Nucleoside analogs such as the anti-HIV drug AZT constitute nearly half of approved antiviral and anticancer drugs, and pronucleotides have even better drug properties, making them a growing focus of drug discovery efforts. For nucleoside analogs to do their jobs—blocking nucleic acid synthesis or inducing cell death—cells must shepherd them inside through membrane transporter proteins. T...