R.A. Klein Nijenhuis
- [2+2]-Photocycloaddition in natural product synthesis
- Formal synthesis of solanoeclepin A and total syntheses of aquatolide, wilfolide B and related terpenes
- Award date
- 17 May 2018
- Number of pages
- Document type
- PhD thesis
- Faculty of Science (FNWI)
[2+2]-Photocycloaddition is a powerful method to synthesise highly strained, complex and multicyclic compounds. The research described in this thesis focusses on using this reaction to pursue the total synthesis of a number of complex natural products. The main project focusses on the synthesis of solanoeclepin A, an extremely potent hatching agent of the potato cyst nematode. To reach this goal, the molecule was divided in two parts, the left- and the right-hand substructure.
With the left-hand substructure completed in previous research, the goal was now to synthesise the right-hand substructure, and to complete the total synthesis by connecting the two fragments. The key step is a [2+2]-photocycloaddition of 2-substituted 3-methyl-2-cyclohexenones, described in chapter 3. Using this reaction the highly strained bicyclo[2.1.1]cyclohexane core structure of the natural product was accessed from simple starting materials in a few steps. A racemic approach to the right-hand substructure of solanoeclepin A is described in chapter 2. Extensive research ultimately led to a short and efficient enantioselective formal synthesis of solanoeclepin A, as described in chapter 4. Finally, the efforts to combine both fragments are described in chapter 5.
The final chapter describes the first total syntheses of aquatolide and wilfolide B. Aquatolide was prepared using the [2+2]-photocycloaddition of an allene-substituted pentenolide, ultimately leading to the natural product. Retro-ene type rearrangement of the cycloaddition product led to a different carbon skeleton, leading to the successful total synthesis of wilfolide B.
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