Theoretical Study on the Biosynthesis of the Mandapamates: Mechanistic Insights Using Density Functional Theory

Wang, Di; Pattenden, Gerald; Fow, Kam Loon; Stocks, Michael J.; Hirst, Jonathan D.; Tang, Bencan

Abstract

Density functional theory (B3LYP-D3(BJ) and ωB97XD) calculations have been used to assess the stereochemical outcomes of the proposed transannular [4 + 2] cycloaddition pathway for the biosynthesis of mandapamate and isomandapamate from macrocyclic intermediates. Calculations reveal that the topological shift between macrocyclic conformers is vital in controlling the stereoselectivity of the downstream steps toward the isomeric mandapamates. A stepwise 4 + 2 type process is energetically favored over a concerted [4 + 2] pathway at room temperature, and is consistent with the stereochemistries found in the natural products.

Citation

Wang, D., Pattenden, G., Fow, K. L., Stocks, M. J., Hirst, J. D., & Tang, B. (2024). Theoretical Study on the Biosynthesis of the Mandapamates: Mechanistic Insights Using Density Functional Theory. Journal of Organic Chemistry, 89(18), 12946-12956. https://doi.org/10.1021/acs.joc.4c00859

• Journal Article Type: Article
• Acceptance Date: Aug 23, 2024
• Online Publication Date: Sep 9, 2024
• Publication Date: Sep 20, 2024
• Deposit Date: Sep 14, 2024
• Publicly Available Date: Sep 17, 2024
• Journal: Journal of Organic Chemistry
• Print ISSN: 0022-3263
• Electronic ISSN: 1520-6904
• Publisher: American Chemical Society
• Peer Reviewed: Peer Reviewed
• Volume: 89
• Issue: 18
• Pages: 12946-12956
• DOI: https://doi.org/10.1021/acs.joc.4c00859
• Public URL: https://nottingham-repository.worktribe.com/output/39465020
• Publisher URL: https://pubs.acs.org/doi/10.1021/acs.joc.4c00859