A protecting-group-free synthesis of (+)-nephrosteranic, (+)-protolichesterinic, (+)-nephrosterinic, (+)-phaseolinic, (+)-rocellaric acids and (+)-methylenolactocin

Abstract

A collective synthesis of a γ-butyrolactone class of paraconic acids such as (+)-methylenolactocin, (+)-phaseolinic acid, (+)-nephrosteranic acid, (+)-nephrosterinic acid, (+)-rocellaric acid and (+)-protolichesterinic acid is described. The strategy adopted is protecting-group-free based on efficient Pd-catalyzed Suzuki-Miyaura coupling and Ru-catalyzed Sharpless oxidation to construct the core β-COH-γ-butyrolactone unit to accomplish the synthesis of various paraconic acids.

Evolution of Strategies in Paraconic Acids Synthesis

“…In 2017, we developed a catalytic protecting‐group‐free (PGF) synthesis of several paraconic acids including (+)‐methylenolactocin and (+)‐phaseolinic acid (Scheme ) . The Midland reduction of 98 to 85 (70%, 94% ee) and then Pd‐catalyzed hydrostannylation, lactonization and iodination delivered β‐iodobutenolide 99 .…”

“…In continuation to our interest in paraconic acids, we later in 2017 achieved a protecting‐group‐free synthesis of (+)‐nephrosterinic acid ( 2 a ) and (+)‐protolichesterinic acid ( 2 b ) (Scheme ). This strategy relied on efficient Pd‐catalyzed Suzuki–Miyaura coupling and Ru‐catalyzed Sharpless oxidation to construct the β‐CO 2 H‐γ‐butyrolactone core.…”

“…In 2017, we achieved a collective synthesis of several paraconic acids based on a protecting‐group‐free (PGF) approach involving Midland reduction and Suzuki−Miyaura coupling with ligand 100 developed by us (Schemes and ). The advanced intermediates 117 b and 117 a prepared in Scheme could also be diverted in the total synthesis of nephrosteranic acid and roccellaric acid (Scheme ).…”

Light on the Horizon: Current Research and Future Perspectives in Flow Photochemistry

“…84 γ-Butyrolactones are reported to be building blocks for the preparation of biologically relevant molecules and are present in many natural products, such as paraconic acids and trisubstituted γ-butyrolactones, which show antibiotic and antitumor properties. 85 With a simple methodology, this kind of heterocyclic compound could be synthesized using a lab-scale mesofluidic reactor with inline NMR spectroscopy, enabling fast optimization of the reaction parameters. Under optimized conditions, a family of γ- butyrolactones was obtained on a scale-up methodology to 12 g day −1 in a short time with moderate to high isolated yields (47−76%) (Scheme 20).…”

“…Monbaliu and co-workers have reported a photochemical radical addition of isopropanol-derived to maleic or fumaric acid to obtain γ-butyrolactone scaffolds under scalable continuous-flow conditions . γ-Butyrolactones are reported to be building blocks for the preparation of biologically relevant molecules and are present in many natural products, such as paraconic acids and trisubstituted γ-butyrolactones, which show antibiotic and antitumor properties . With a simple methodology, this kind of heterocyclic compound could be synthesized using a lab-scale mesofluidic reactor with inline NMR spectroscopy, enabling fast optimization of the reaction parameters.…”