1. Partial Synthesis of Heliotridane
Brady Barron, Dr. Zercher
Department of Chemistry, University of New Hampshire, Durham, New Hampshire 03824
12/09/16
The crude, methylated product from the final completed reaction could be purified via column chromatography so that it may be subjected to enolate-mediated ring-cleavage conditions to yield the ring-opened product 5. A zinc-mediated chain-extension reaction could then be used to yield 6. The extended chain could then be reduced and undergo a reductive amination when introduced to harsh basic conditions, thus creating a pyrrolizidine nucleus and yielding the desired product, heliotridane 1.
Scheme 3. Possible Future Work to Complete the Synthesis of Heliotridane
The synthesis of the target compound was not successfully completed. Only the first two steps of the synthesis were completed to yield 1-(carbo-t-butoxy)-3-methyl-2-oxopyrrolidone 4. Improved lab techniques and further experimental work could be done to complete the synthesis.
I would like to thank Dr. Zercher and his research group, Bill Butler, and the University of New Hampshire Chemistry Department.
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Keck, G.E., Cressman, E.N.K., and Enholm, E.J. Intramolecular allylstannane cyclizations in alkaloid synthesis: applications to pyrrolizidine alkaloids. The Journal of Organic Chemistry., (18),
Kennedy, D.P., Studies Directed Toward the Total Synthesis of (±)-Heliotridane. B.S Dissertation, University of New Hampshire, 2002.
Future Work:
Pyrrolizidine alkaloids are a type of toxin found in plants known to cause toxic reactions in humans, but some of these toxins have health benefits including antitumor properties and uses in treatment of conditions such as skin ailments1. The simplest and most useful pyrrolizidine alkaloid, (±)-heliotridane, has been synthesized for over 50 years and is recognized for its simple structure and use as a synthetic precursor to other, more complex pyrrolizidine alkaloids2. The zinc-mediated chain-extension reaction proposed by the Zercher group is crucial in the syntheses of heliotridane and other medically useful pyrrolizidine alkaloids3. This project explores one of the many possible synthetic pathways for compound 1, heliotridane. 1
Figure 1. Heliotridane
The starting material, 2-pyrrolidone 2, was protected with dicarboxy di-tert-butyl anhydride to yield 1-(tert-butoxycarbonyl)-2-pyrrolidone 3. The Boc–protected lactam was then methylated via treatment with methyl iodide in to form 1-(carbo-t-butoxy)-3-methyl-2-oxopyrrolidone 4. The methylated product is an intermediate in the overall synthesis of compound 1, heliotridane. All intermediates were analyzed and identified via 1H NMR and TLC.
Introduction:
Scheme 1. Pathway to the Target Compound, Heliotridane.
The Boc protection of the starting material was performed successfully with a yield of 83%. The crude methylated product was obtained in a moderate yield of 63%. Due to lack of time, the remaining reactions in the synthesis could not be performed.
Scheme 2. Experimental Progress Towards the Synthesis of Heliotridane
Figure 2. 1H NMR Spectra of Purified 3.
Figure 3. 1H NMR Spectra of Crude 4.
Results and Discussion: 1 6
Conclusions:
Acknowledgements:
Experimental Design:
References: