Department or Administrative Unit
Chemistry
Document Type
Article
Creative Commons License
This work is licensed under a Creative Commons Attribution-Noncommercial 3.0 License
Author Copyright
© 2022 The Author(s). Published by the Royal Society of Chemistry
Publication Date
6-14-2022
Journal
RSC Advances
Abstract
C-fused γ-lactam-lactones are resident in several bioactive molecules, including anticancer agents such as omuralide. In this embodiment, we report mild conditions for the catalytic halolactonization of lactam-tethered 5-aryl-4(E)-pentenoic acids. The use of dichloromethane as the solvent and Ph3PS as the catalyst led to predominant 6-endo-trig cyclization and furnished the trans-fused-γ-lactam-δ-lactones. The transformation is modular, regioselective, chemoselective, and diastereoselective. The γ-lactam-δ-lactones bear angular quaternary benzylic stereocenters, which is noteworthy since the presence of a quaternary carbon in bioactive small molecules often promotes an element of conformational restriction that imparts potency, selectivity, and metabolic stability. The generated halogen and lactone motifs are important functional handles for late-stage diversification.
Recommended Citation
Beng, T. K., Rodriguez, M. J., & Borg, C. (2022). Stereocontrolled access to δ-lactone-fused-γ-lactams bearing angular benzylic quaternary stereocenters. RSC Advances, 12(27), 17617–17620. https://doi.org/10.1039/d2ra02167f
Included in
Medicinal and Pharmaceutical Chemistry Commons, Medicinal-Pharmaceutical Chemistry Commons
Comments
This article was originally published open access in RSC Advances. The full-text article and supplemental information from the publisher can be found here.