Work

Total Synthesis of Small Molecule Natural Product: 7-Hydroxy-6-methoxyquinolin-2(1 H )-one, Its Variants, and Quinolin-2-yl Esters

Year: 2025

Type: article

Abstract: High Resolution Image Download MS PowerPoint Slide 7-Hydroxy-6-methoxyquinolin-2(1 H )-one (HMQ) is one of the active components of the natural product, Spondias pinnata, reported to have very high antioxidant and anti-inflammatory activities. Low bioavailability and scalability limit its bioapplications. Herein, a simple and elegant synthetic route has been developed to form HMQ and its variants. Anilines were coupled with cinnamoyl chloride/3,4,5-trimethoxycinnamoyl chloride to form cinnamanilides. They were then cycloeliminated in the presence of TfOH at RT-110 °C, to form quinolin-2(1 H )-ones in 62–97% yield. In addition to spectroscopic characterization, the structures of the natural product and its regioisomer were unambiguously established by a single-crystal XRD study. The developed protocol can be adopted for the gram-scale synthesis of HMQ. Furthermore, a series of HMQ variants were synthesized, offering SAR evaluation for bioactivity studies. The scope of the process is demonstrated with the synthesis of 21 quinolin-2-yl esters from the corresponding quinolin-2(1 H )-ones.

Source: ACS Omega

DOI: 10.1021/acsomega.5c09228

Authors: Kunj Talati, Saravanakumar Rajendran

Institution: Vellore Institute of Technology University

Language: English

Topic: Advanced Synthetic Organic Chemistry

Subfield: Organic Chemistry

Field: Chemistry

Domain: Physical Sciences

Open Access status: gold

Estimated APC paid: $1,935

Funder: Department of Science and Technology, Ministry of Science and Technology, India