| Summary: | <p>Cycloisomerization is a powerful strategy and a highly efficient approach in the rapid construction of polycyclic ring systems of complex natural products from acyclic polyunsaturated precursors. This thesis aims to employ palladium-catalyzed ynamide cycloisomerization strategy as a key step towards the synthesis of natural products alkaloids gelsemine and peduncularine. Two individual projects have been completed.</p>
<p>In the course of synthesis of the gelsemine core, we first designed and tested the three separate model systems (model fused ring synthesis, model N-tosyl spiro ring synthesis and model carbamate spiro ring synthesis) to develop the individual ynamide cycloisomerization and based on the kinetic studies between these model systems, we demonstrated the timeresolved, one-pot, palladium-catalyzed double cycloisomerization cascades where two discrete ring-forming event was occurred in a sequential manner.</p>
<p>In the second project, to further apply the ynamide cycloisomerization as a synthetic tool towards the synthesis of peduncularine, we were able to generate the unusual 6-azabicyclo[3.2.1]oct-3-ene framework of peduncularine, together with the generation of its (indol-3-yl)methylene motif in a single step on the gram scale, differing from other reports which reply on the Fisher indole synthesis. We subsequently completed the total synthesis of pseudo-peduncualrine and 7-epi-pseudo-peduncularine in the longest linear sequence of 14 and 12 steps respectively from commercially available cyclohexa-1,3-diene in a scalable manner.</p>
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