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

• Published in: Medicinal chemistry research 2019-04, Vol.28 (4), p.473-484
• Main Authors: Solorio-Alvarado, César R., Ramadoss, Velayudham, Gámez-Montaño, Rocío, Zapata-Morales, Juan R., Alonso-Castro, Angel J.
• Format: Article
• Language: English
• Subjects: Alkaloids; Biochemistry; Biomedical and Life Sciences; Biomedicine; Breast cancer; Cancer; Cell Biology; Construction; Homology; Natural products; Organic chemistry; Original Research; Pharmacology/Toxicology; Ring opening; Synthesis; Tumor cell lines
• ISSN: 1054-2523; 1554-8120
• DOI: 10.1007/s00044-019-02290-z

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.