Synthesis and Biological Evaluation of Some Enantiomerically Pure C8c–C15 Monoseco Analogues of the Phenanthroquinolizidine-Type Alkaloids Cryptopleurine and Julandine*

Magne O. Sydnes; Anna Bezos; Christopher Burns; Irma Kruszelnicki; Christopher R. Parish; Stephen Su; A. David Rae; Anthony C. Willis; Martin G. Banwell

doi:10.1071/CH08190

RESEARCH ARTICLE

Synthesis and Biological Evaluation of Some Enantiomerically Pure C8c–C15 Monoseco Analogues of the Phenanthroquinolizidine-Type Alkaloids Cryptopleurine and Julandine^*

Magne O. Sydnes ^A , Anna Bezos ^B , Christopher Burns ^C , Irma Kruszelnicki ^C , Christopher R. Parish ^B , Stephen Su ^C , A. David Rae ^A , Anthony C. Willis ^A and Martin G. Banwell ^A ^D

+ Author Affiliations

- Author Affiliations

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

^B John Curtin School of Medical Research, Institute of Advanced Studies, Australian National University, Canberra, ACT 0200, Australia.

^C Cytopia Pty Ltd, 576 Swan Street, Richmond, VIC 3121, Australia.

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

Australian Journal of Chemistry 61(7) 506-520 https://doi.org/10.1071/CH08190
Submitted: 5 May 2008 Accepted: 26 May 2008 Published: 16 July 2008

Abstract

A series of enantiomerically pure C8c–C15 monoseco analogues, 23–30, of the alkaloids cryptopleurine (1) and julandine (2) have been prepared using cinnamyl chloride 37 and (S)- or (R)-2-methylpiperidine as key building blocks. Two related compounds, 31 and 32, have also been synthesized. Each of these analogues has been subjected to various biological evaluations and most of them show dramatically reduced cytotoxicity compared with parent system 1. Nevertheless, they are potent anti-angiogenic agents. The formation and single-crystal X-ray analysis of the spirocyclic dienone 54, a by-product arising from attempts to prepare analogue 32, is also described.

Acknowledgements

We thank the Institute of Advanced Studies for financial support including the provision of a PhD Scholarship to MOS. Dr Paul Savage of CSIRO Molecular Science (Melbourne) is thanked for providing an authentic sample of the alkaloid cryptopleurine (1). CRP and AB are supported by an NHMRC Program grant.

References

^* Aspects of this work have been reported in preliminary form: M. G. Banwell, A. Bezos, C. Burns, I. Kruszelnicki, C. R. Parish, S. Su, M. O. Sydnes, Bioorg. Med. Chem. Lett. 2006, 16, 181.

Synthesis and Biological Evaluation of Some Enantiomerically Pure C8c–C15 Monoseco Analogues of the Phenanthroquinolizidine-Type Alkaloids Cryptopleurine and Julandine*

Abstract

Acknowledgements

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Synthesis and Biological Evaluation of Some Enantiomerically Pure C8c–C15 Monoseco Analogues of the Phenanthroquinolizidine-Type Alkaloids Cryptopleurine and Julandine^*