Reduction carves path to chiral compounds

Abstract

Many pharmaceuticals need to be a certain shape to fit into the binding pocket of the enzyme they target. Synthesizing molecules with the desired chirality requires controlled addition of functional groups, which is challenging. Now Pengwei Xu and Zhongxing Huang from the University of Hong Kong have made this process a little easier. They found a way to transform malonic esters into chiral compounds with four different carbon substituents ( Nat. Chem . 2021, DOI: 10.1038/s41557-021-00715-0 ) . The chemists created six classes of molecules containing a variety of functional groups, which wasn’t possible with prior methods. Previously, researchers used pig liver esterases to transform malonic esters into chiral compounds. But these enzymes don’t work well when the esters have bulky side groups or multiple side groups similar in size, which limits the enzymes’ utility. The team used cheap starting materials to make a library of malonic esters of different