Microbiological Bioreduction of Bulky–Bulky Pyrimidine Derivatives as an Alternative to Asymmetric Chemical Synthesis

Heterocyclic scaffolds are often present in many natural and non-natural products with important biological activity, such as synthetic intermediates used to synthesise many drugs. Among others, heterocycles based on a pyrimidine ring may have antioxidant, antibacterial, antiviral, antifungal, antituberculosis, and anti-inflammatory properties. The present study investigated commercially available microbial biocatalysts in the enzymatic desymmetrization reaction of bulky–bulky ketones derived from pyrimidine bases. The influence of some parameters on the efficiency of biocatalysis, i.e., the substrate concentration and pH of the reaction medium, was evaluated. In the one-step bioreduction catalysed by Saccharomyces cerevisiae, secondary alcohols with a defined absolute configuration were obtained with high enantiomeric excess up to 99% ee and moderate conversion. Biocatalysis offers economic and environmental benefits as an alternative to conventional methods, becoming a powerful tool in the synthesis of crowded alcohols.