Production of biorenewable, enantiopure (S)-3-hydroxy-γ-butyrolactone for pharmaceutical applications

Abstract

The high price of pharmaceuticals is driven, in part, by the cost of materials and production. Some of the most expensive drugs contain chiral centers that are introduced during synthesis using a small number of chemical building blocks. These building blocks are both costly to produce and can lead to significant greenhouse gas emissions, both due to difficult recovery from low-concentration mixtures of chemical species and challenging reaction pathways. This work reports on a new approach for synthesizing pharmaceutical precursors that allows for the production of chiral species at high concentrations and yields, in water, and at room temperature. The reaction pathway starts with renewable glucose that is chemically pruned using biological catalysis to produce a highly reactive intermediate that is then converted by acid/ base catalysis to the key chiral building block used to make statin drugs, (S)-3-hydroxy-γ-butyrolactone (HBL). This pathway reduces the cost of HBL by more than 60% relative to the state of the art that uses non-renewable, petroleum-derived feedstocks.

Citation

Waters, Justin O.P.; Jamalzade, Elnaz; Abdulrazzaq, Hussein T.; Kuch, Nathaniel; Gunukula, Sampath R.; Dumesic, James A.; Kersten, Philip J.; Schwartz, Thomas J. 2025. Production of biorenewable, enantiopure (S)-3-hydroxy-γ-butyrolactone for pharmaceutical applications. Chem. 11: 102665. 12 p. https://doi.org/10.1016/j.chempr.2025.102665.