Journal article

Synthesis and Biological Evaluation of (-) and ( )-Spiroleucettadine and Analogues

Michael P Badart, Emma M Barnes, Andrew P Cording, Selena CL Gilmer, Ian D Billinghurst, Veera V Shivaji R Edupuganti, Guillaume Lessene, Abigail R Bland, Rebekah L Bower, Zohaib Rana, Scott A Ferguson, Helen K Opel Reading, Gregory M Cook, Rhonda J Rosengren, Kurt L Krause, Allan B Gamble, John C Ashton, Bill C Hawkins

CHEMMEDCHEM | WILEY-V C H VERLAG GMBH | Published : 2021

Abstract

A second-generation enantiospecific synthesis of spiroleucettadine is described. The original reported antibacterial activity was not observed when the experiment was repeated on the synthetic samples; however, significant anti-proliferative activity was uncovered for both enantiomers of spiroleucettadine. Comparison of the optical rotational data and ORD-CD spectra of both enantiomers and the reported spectrum from the natural source have not provided a definitive answer regarding the absolute stereochemistry of naturally occurring spiroleucettadine. Efforts then focussed on alteration at the C-4 and C-5 positions of the slightly more active (-)-spiroleucettadine. Ten analogues were synthes..

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Grants

Funding Acknowledgements

We acknowledge the University of Otago for a Research grant (UORG). MPB and APC gratefully acknowledge the University of Otago for the provision of PhD scholarships. We thank the National Cancer Institute (NCI) for the preliminary testing of spiroleucettadine against the NCI-60 panel of cancer cells.