Model Studies on the Enzyme-Regulated Stereodivergent Cascade Passerini Reaction

The synthesis of chiral alpha-acyloxy carboxamides containing two stereogenic centers continues to be a challenging field of organic chemistry. Herein, we have proposed and proved the feasibility of an enzyme regulated-cascade reaction, which using the same substrates enables the formation of individual stereoisomers of alpha-acyloxy carboxamides with up to 99 % ee. The access to the individual stereoisomeric products has been achieved by a combination of the enzymatic kinetic resolution of racemic vinyl esters, subsequent Passerini reaction, and enzymatic kinetic resolution of formed alpha-acyloxy carboxamides. The presented studies are promising in exploratory proof-of-concept of enzyme-controlled stereodivergent cascade to form an important class of chiral compounds for medicinal chemistry.

Automated summary

The study introduces and validates an enzyme-regulated cascade reaction for efficient synthesis of chiral compounds with two stereogenic centers. Through enzymatic kinetic resolution, high-purity individual stereoisomeric products are successfully synthesized.