Total synthesis of the linear and angular 3-methylated regioisomers of the marine natural product Kealiiquinone and biological evaluation of related Leucetta sp. alkaloids on human breast cancer
- 237 Downloads
A straightforward, concise, and building block-scalable, seven-step total synthesis of the unnatural 3-methylated regioisomer analog of the marine alkaloid kealiiquinone is described. The construction by a regioselective way of the 4-anisyl-3-methylbenzimidazolone core of this analog, as well as the homologation of the aromatic π-system through a 4π ring opening/6π ring closure sequence for the 1,4-quinoid ring construction by using the squaric acid chemistry, are the key features of this procedure. In light that only one total synthesis of this 3-methyl-iso-kealiiquinone has been described by using a Friedel−Crafts reaction as the key step, herein, we present our pericyclic-based strategy which was successfully concluded with the aforementioned alkaloid synthesis. The biological evaluation of these unnatural derivatives was carried out on MDA-MB231 human cancer cell lines of breast. The cis-platin (CDDP) was used as a positive control of activity.
KeywordsTotal synthesis Kealiiquinone Structural analogs Marine alkaloids Marine sponges Leucetta sp
We are grateful to CONACyT (CB-2013/220836) for financial support. We acknowledge the facilities of the DCNyE, the Chemistry Department, and the National Laboratory UGCONACyT (LACAPFEM) of the University of Guanajuato for full characterization. We also thank CONACyT for fellowships to V.R.
Compliance with ethical standards
Conflict of interest
The authors declare that they have no conflict of interest.
- Bergmann W, Stempien MF (1957) Contributions to the study of marine products. XXXIX. The nucleosides of sponges. III. spongothymidine and spongouridine. J Org Chem 2:1557–1575Google Scholar
- Hassanloie N, Zeynizadeh B, Ashuri S, Hassanloie F (2014) NaBH4/NiCl2·6H2O: a green synthetic method for fast and convenient reduction of nitroarenes in water as green solvent. Open Cancer Immunol J 59–62Google Scholar
- Ramadoss V, Nahide PD, Juárez-Ornelas K, Rentería-Gómez M, Ortiz-Alvarado R, Solorio-Alvarado CR (2016) A four-step scalable formal synthesis of ningalin C. ARKIVOC IV:385–394Google Scholar