Application of the Palladium(0)-Catalyzed Ullmann Cross-Coupling Reaction in a Total Synthesis of (±)-Aspidospermidine and thus Representing an Approach to the Lower Hemisphere of the Binary Indole–Indoline Alkaloid Vinblastine*

Martin G. Banwell; David W. Lupton; Anthony C. Willis

doi:10.1071/CH05181

RESEARCH ARTICLE

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Application of the Palladium(0)-Catalyzed Ullmann Cross-Coupling Reaction in a Total Synthesis of (±)-Aspidospermidine and thus Representing an Approach to the Lower Hemisphere of the Binary Indole–Indoline Alkaloid Vinblastine*

Martin G. Banwell ^A ^B , David W. Lupton ^A and Anthony C. Willis ^A

+ Author Affiliations

- Author Affiliations

^A Research School of Chemistry, Institute of Advanced Studies, Australian National University, Canberra ACT 0200, Australia.

^B Corresponding author. Email: mgb@rsc.anu.edu.au

Australian Journal of Chemistry 58(10) 722-737 https://doi.org/10.1071/CH05181
Submitted: 1 August 2005 Accepted: 22 September 2005 Published: 8 November 2005

Abstract

As part of ongoing studies directed towards the construction of the anti-cancer agent vinblastine (1), the related but structurally less complex natural product aspidospermidine (3) has been synthesized. Two approaches to target 3 were pursued. In the first, which was unsuccessful, the amine-tethered enone 6 was prepared but this failed to engage in the pivotal intramolecular conjugate addition reaction to give the bicyclic system 5. In contrast, the related compound 46, incorporating tethered enone and azide moieties, engaged in an intramolecular 1,3-dipolar cycloaddition reaction to give, presumably via an intermediate triazoline, the isolable and ring-fused aziridine 47. This was then converted, over two steps, into the previously reported tetrahydrocarbazole 4. Application of established protocols to this last compound allowed for the installation of the E-ring of the title alkaloid 3 and completion of the total synthesis.

Acknowledgements

We thank the Institute of Advanced Studies as well as the Australian Research Council Discovery Program for generous financial support. D.W.L. would like to thank Drs Regan J. Thomson, Jens Renner, and Oliver E. Hutt, as well as Dr Darragh O’Neil for helpful discussions.

References

^* Aspects of this work have been presented in preliminary form: M. G. Banwell, D. W. Lupton, Org. Biomol. Chem. 2005, 3, 213. doi:10.1039/B415977B

^† The S-enantiomer of compound 18 has been reported: see ref. [14].

Application of the Palladium(0)-Catalyzed Ullmann Cross-Coupling Reaction in a Total Synthesis of (±)-Aspidospermidine and thus Representing an Approach to the Lower Hemisphere of the Binary Indole–Indoline Alkaloid Vinblastine*

Abstract

Acknowledgements

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