Stereoselective synthesis of novel carbocyclic and heterocyclic scaffolds of medicinal importance from biocatalytically derived enantiopure α-substituted-β-hydroxy esters

Abstract

Biocatalytically derived enantiopure α-substituted-β-hydroxy esters can act as a potential precursor for the stereoselective synthesis of a diverse set of small organic molecules of medicinal importance. Chiral γ-Z-butenolides can be constructed through a “Pd–Cu” bimetallic cascade cyclization. Synthetic anti-viral compound 5′-methylaristeromycin was accessed through RCM (ring closing metathesis) and nucleophilic opening of epoxide with nucleobase adenine. Structurally novel enantiopure cyclitol analogs were synthesized efficiently through RCM reaction, enzymatic desymmetrization, and cyclopropanation reaction starting from the same precursor. Chiral cyclic γ-keto-ester was accessed by exploration of asymmetric Stetter reaction from the same starting material. Finally, novel bicyclic enones can also be synthesized through RCM/Robinson annulation sequence. All the synthesized compounds can be potentially useful in medicinal chemistry research.