Theoretical Study on the Biosynthesis of the Mandapamates: Mechanistic Insights Using Density Functional Theory
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.
Authors
- Kam Loon Fow (ORCID: https://orcid.org/0000-0002-8165-9477)
- Gerald Pattenden
- Jonathan D. Hirst (ORCID: https://orcid.org/0000-0002-2726-0983)
- Michael J. Stocks (ORCID: https://orcid.org/0000-0003-3046-137X)
- Bencan Tang (ORCID: https://orcid.org/0000-0002-4301-2496)
- Di Wang (ORCID: https://orcid.org/0000-0001-9817-7047)
Institutions
- University of Nottingham Ningbo China (CN)
- University of Nottingham (GB)
Publication Details
- Journal
- The Journal of Organic Chemistry
- Published
- 2024-09-09
- DOI
- https://doi.org/10.1021/acs.joc.4c00859
- Citations
- 1
- Primary Topic
- Plant biochemistry and biosynthesis
- Type
- article
- Field-Weighted Citation Impact
- 0.23
Funders
- Royal Academy of Engineering
- University of Nottingham
- National Natural Science Foundation of China
- Ministry of Science and Technology of the People's Republic of China
- Ningbo Municipal Bureau of Science and Technology
- Natural Science Foundation of Ningbo
- School of Chemistry, University of Nottingham
- National Key Research and Development Program of China
- University of Nottingham Ningbo China
- Science and Technology Department of Zhejiang Province