Synthesis and biological evaluation of (-) and (+)-spiroleucettadine and analogues
- Author(s)
- Badart, M; Barnes, EM; Cording, AP; Gilmer, S; Billinghurst, ID; Edupuganti, V; Lessene, G; Bland, A; Bower, R; Rana, Z; Ferguson, S; Opel Reading, H; Cook, G; Rosengren, R; Krause, K; Gamble, A; Ashton, J; Hawkins, BC;
- Journal Title
- ChemMedChem
- Publication Type
- Journal epub ahead of print
- Abstract
- A second generation enantiospecific synthesis of spiroleucettadine is described. The original reported antibacterial activity was not observed when 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 has 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 position of the slightly more active (-)-spiroleucettadine. Ten analogues were synthesised, with three analogues ( 21 , 22 and 24 ) found to possess similar anti-proliferative profiles to spiroleucettadine ( 3 ) against the H522 lung cancer cell line (0.31 μM, 0.38 μM and 0.28 μM vs 0.28 μM, respectively).
- Publisher
- Wiley
- Keywords
- Hypervalent iodine; Medicinal Chemistry; alkaloids; oxidative spirocyclization; total synthesis
- Research Division(s)
- Chemical Biology
- PubMed ID
- 33320428
- Publisher's Version
- https://doi.org/10.1002/cmdc.202000954
- Terms of Use/Rights Notice
- Refer to copyright notice on published article.
Creation Date: 2021-02-01 12:08:36
Last Modified: 2021-03-02 03:03:50