1. Synthesis and Biological Evaluation of (−) and (+)‐Spiroleucettadine and Analogues
- Author
-
Andrew P. Cording, Guillaume Lessene, Rebekah L. Bower, Ian D. Billinghurst, Emma M. Barnes, Bill C. Hawkins, Michael P. Badart, Veera V. Shivaji R. Edupuganti, Kurt L. Krause, Rhonda J. Rosengren, Zohaib Rana, Abigail R. Bland, Helen K. Opel Reading, Gregory M. Cook, Selena C. L. Gilmer, John C. Ashton, Allan B. Gamble, and Scott A. Ferguson
- Subjects
Pharmacology ,010405 organic chemistry ,Chemistry ,Stereochemistry ,Spiroleucettadine ,Organic Chemistry ,Imidazoles ,Lung cancer cell line ,Total synthesis ,Antineoplastic Agents ,Stereoisomerism ,01 natural sciences ,Biochemistry ,0104 chemical sciences ,010404 medicinal & biomolecular chemistry ,Cell Line, Tumor ,Drug Discovery ,Natural source ,Humans ,Molecular Medicine ,Spiro Compounds ,General Pharmacology, Toxicology and Pharmaceutics ,Enantiomer ,Antibacterial activity ,Biological evaluation - 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 synthesised, with three analogues found to possess similar anti-proliferative profiles to spiroleucettadine against the H522 lung cancer cell line.
- Published
- 2021