Synthesis of 12-epi-ent-polyalthenol an antitumour indole sesquiterpene alkaloid

• Published in: Tetrahedron 2012-09, Vol.68 (38), p.7932-7940
• Main Authors: Marcos, Isidro S., Moro, Rosalina F., Costales, Isabel, Basabe, Pilar, Díez, David, Mollinedo, Faustino, Urones, Julio G.
• Format: Article
• Language: English
• Subjects: Alicyclic compounds, terpenoids, prostaglandins, steroids; Alkaloids; Antineoplastic agents; Antitumour; Biological and medical sciences; Biotechnology; Cellular; Chemistry; ent-Halimic acid; Exact sciences and technology; General aspects; Heterocyclic compounds; Heterocyclic compounds with only one n hetero atom and condensed derivatives; Human; Indole sesquiterpenes; Indoles; Medical sciences; Natural products; Organic chemistry; Pharmacology. Drug treatments; Polyalthenol; Preparations and properties; Synthesis; Terpenoids; Tetrahedrons
• ISSN: 0040-4020; 1464-5416
• DOI: 10.1016/j.tet.2012.07.010

The synthesis of 12-epi-ent-polyalthenol, 10, and its epimer at C-19, 11, from ent-halimic acid as starting material has been carried out. The structure of the natural product polyalthenol 1 is confirmed in this way. The synthesized indole sesquiterpenes 10 and 11 and their acetylderivatives 32 and 33 inhibited cellular proliferation of a number of human leukaemic and solid tumour cell lines. [Display omitted] 12-Epi-ent-polyalthenol has been synthesized from ent-halimic acid. The indole sesquiterpenes synthesized inhibit proliferation of several human tumour cells, including leukemic and solid tumour cells, with an IC50 in the range of 25 μM.