Uses and production of chiral 3-hydroxy-γ-butyrolactones and structurally related chemicals

Abstract

Enantiopure (S)-3-hydroxy-gamma-butyrolactone (HGB) and its structurally related C3-C4 chemicals are an important target for chiral building blocks in synthetic organic chemistry. For the production of these compounds, more economical and practical synthetic routes are required. To date, chiral HGBs have been produced from petrochemicals and biomass, especially malic acids and carbohydrates. This report provides a short review on the production and application of enantiopure HGBs and their related compounds. Emphasis is focused mainly on synthetic routes using biocatalysis (microbial and chemoenzymatic) and application of these compounds. Biological methods have concentrated on devising different kinds of enzymes for the synthesis of the same compound as shown in the case of hydroxynitrile, a key intermediate of synthetic statins, and integrating unit processes for the optically active HGBs and 4-chloro-3-hydroxybutyrate with recombinant microorganisms expressing multiple enzymes. Chemical methods involve selective hydrogenation of carbohydrate-based starting materials. Both types of pathways will require further improvement to serve as a basis for a scalable route to HGBs and related compounds. Several of their synthetic applications are also introduced.