Stereoselective synthesis of novel carbocyclic and heterocyclic scaffolds of medicinal importance from biocatalytically derived enantiopure α-substituted-β-hydroxy esters. (13th August 2021)

• Record Type: Journal Article
• Authors: Barik, Rasmita; Halder, Joydev; Jana, Palas; Nanda, Samik
• Is Part Of: Tetrahedron. Volume 94(2021)
• Publication Date: 2021-08-13
• Subjects: Biocatalytic RDKR -- Asymmetric synthesis -- Synthetic antiviral compounds -- Novel γ-Z-butenolides -- Novel carbocyclic scaffolds; Chemistry, Organic -- Periodicals; 547.005
• DOI: 10.1016/j.tet.2021.132356
• Languages: English
• ISSNs: 0040-4020

Abstract

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. Graphical abstract: Structurally unique enantiopure small ring carbocyclic and heterocyclic scaffolds with medicinal importance have been synthesized starting from biocatalytically derived α-substituted-β-hydroxy esters. Bimetallic cascade cyclization, Stetter reaction, Robinson annulation/RCM (ring-closing metathesis) reactions are few key transformations employed to access skeletally diverse chiral organic molecules. Image 1