Urease: A highly biocompatible catalyst for switchable Biginelli reaction and synthesis of 1,4-dihydropyridines from the in situ formed ammonia

• Urea is a natural odorless source of nitrogen for synthesis of 1,4-dihydropyridines.
• Water-based reaction with urea and urease is highly biocompatible.
• Reactions give excellent yields of products without purification.
• Urease catalyzes Hantzsch reaction with urea in water more than NH4OAc.
• This enzymatic medium is reusable and inhibits by heavy metal cations.

Urease is a superior biocompatible catalyst for switching from the Biginelli reaction to urea-based synthesis of 1,4-dihydropyridines in water, where 100% switching occurs at 0.02 g/mL of enzyme. Hantzsch reaction with ammonium acetate (NH4OAc) is inefficiently catalyzed by urease (70%, 4 h), and heavy metal ions inhibit the urease-catalyzed reactions with urea or NH4OAc. Promotion of the urea-based Hantzsch reaction by urease and its inhibition with Hg2 + supports specificity of urease for in situ generation of ammonia, whereas the role of urease in further transformations is not so specific. The features of this enzymatic method are reusability, mild reaction conditions, biocompatibility, generality, and high yield of products.

Urease is a biocatalyst for switching of the Biginelli reaction to urea-based Hantzsch synthesis of 1,4-dihydropyridines in water, while urease-catalyzed Hantzsch reaction with either urea or ammonium salt inhibits by trace amounts of Hg2 + and Ag+.Figure optionsDownload as PowerPoint slide