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Updated: Nov 19, 2025
14:44
Structure and Coordination Determination of Peptide-metal Complexes Using 1D and 2D 1H NMR
Published on: December 16, 2013
9.9K
Metric-Based Analysis of Convergence in Complex Molecule Synthesis
Ian Tingyung Hsu1, Martin Tomanik1, Seth B Herzon1,2
1Department of Chemistry, Yale University, New Haven, Connecticut 06520, United States.
Accounts of Chemical Research
|February 1, 2021
Summary
This study details the synthesis of complex natural products, including alkaloids and diterpenes, using convergent strategies. It also introduces quantitative parameters to assess the efficiency of these synthetic routes.
Area of Science:
- Organic Chemistry
- Synthetic Chemistry
- Natural Product Synthesis
Background:
- Convergent synthesis involves coupling complex intermediates late in a synthetic pathway.
- Assessing the degree of convergence quantitatively is crucial for synthetic design.
- Alkaloids, polyketides, and diterpenes are important classes of natural products with diverse biological activities.
Purpose of the Study:
- To provide an overview of alkaloid, polyketide, and diterpene metabolites synthesized in the laboratory.
- To present quantitative parameters for assessing the degree of convergence in chemical syntheses.
- To highlight the strengths and weaknesses of different convergent synthetic strategies.
Main Methods:
- Synthesis of (-)-kinamycin F, (-)-lomaiviticin aglycon, (-)-huperzine A, hasubanan alkaloids, (+)-batzelladine B, (+)-pleuromutilin, and (-)-myrocin G.
- Utilized key reactions such as oxidative dimerization, three-component coupling, intramolecular α-arylation, acetylide addition, cascade reactions, and nickel-catalyzed reductive cyclization.
- Developed and applied quantitative parameters to evaluate synthetic convergence.
Main Results:
- Successfully synthesized a range of complex natural products, including alkaloids and diterpenes, employing convergent strategies.
- Demonstrated the utility of specific reactions for constructing intricate molecular architectures.
- Established parameters for quantitatively assessing synthetic convergence, including steps post-convergence, fragment preparation time difference, atom percentage at convergence, and coupling step complexity.
Conclusions:
- Convergent synthesis is a powerful strategy for accessing complex natural products.
- Quantitative assessment of convergence provides valuable insights into synthetic efficiency.
- The developed parameters aid in optimizing synthetic routes and understanding the nuances of convergent strategies.
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