Abstract
Spirooxindole alkaloids and their derivatives exhibit excellent biological activities in different aspects bearing a potential of pharmaceutical application. Many synthetic chemists were attracted to synthesize this type of compounds efficiently. In the past 50 years, many elegant synthetic approaches towards the construction of spirooxindole skeletons have been published. However, challenges on the functional group tolerance, synthetic efficiency and the environmental impact on the waste generated are still observed. This thesis is to address the above issues by developing an efficient approach to the construction of spirooxindole skeleton with wide functional group tolerance (Chapter one), demonstrating its application in total syntheses of spirooxindole alkaloid natural products (Chapter two) and developing a green approach to the transformation of spirooxindole by electrochemical oxidation (Chapter three).Chapter one describes a [3+2] cycloaddition of oxindoles and 1-piperideines for the construction of spirooxindole skeleton (SIO). This protocol enables the ease of derivative synthesis by dividing the spirooxindole into two fragments, oxindoles and 1-piperideines. Wide functional groups tolerance allows the introduction of well functionalized 1-piperideine for direct synthesis of desired alkaloids or other late-stage transformation. Chapter two demonstrates the synthetic ability of the developed [3+2] cycloaddition. Two total syntheses of spirooxindole alkaloids, isoformosanine and spirophylline D, are described. The corresponding 1-piperideines are synthesized by piperidinone from a green protocol of aza-Achmatowicz rearrangement of furfurylamine developed by our group.
Chapter three describes an electrochemical approach towards the construction of spirooxindole by the oxidative rearrangement of tetrahydro-β-carboline. Based on our two developed green protocols of oxidative rearrangement by Oxone-KBr and Fenton reaction, electricity is utilized to further reduce the waste generated by traditional chemical oxidants. Presence of LiBr in a zero-gap flow cell setup enable the desired transformation in high yield efficiently which could be applied in drug synthesis in the future.
| Date of Award | 2024 |
|---|---|
| Original language | English |
| Awarding Institution |
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| Supervisor | Rongbiao TONG (Supervisor) |
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