Biobased Route To Chiral Reagents

To construct the statins Lipitor and Crestor, the antibiotic Zyvox, and several other drugs, chemists use the chiral building block 3-hydroxy-γ-butyrolactone (3HBL). But making this specialty chemical requires hazardous processing conditions and an expensive catalyst, which is why it costs about $450 per kg. To remedy that situation, MIT’s Kristala Jones Prather and colleagues created a biosynthetic route to 3HBL and its hydrolyzed form, 3,4-dihydroxybutyric acid, starting from glucose and glycolate or glucose alone (Nat. Commun., DOI: 10.1038/ncomms2418). Prather’s team took an existing enzymatic pathway used to make 3-hydroxybutyrate and 3-hydroxyvalerate and reengineered it to make the more structurally diverse 3-hydroxyacids. The key enzyme is a thiolase that catalyzes a C–C bond-forming Claisen condensation. The researchers acknowledge the pathway will need to be optimized if it’s going to compete with the current industrial process for making these building blocks. Even so, they note that it’s a promising demonstration of an engineered pathway that relies on C–C bond-forming reactions.