Synthesis, reactions and antineoplastic activity of 3-(2-oxo-2H-chromen-3-yl)-2-oxo-2H,5H-pyrano[3,2-c]chromene derivatives

• Published in: Central European journal of chemistry 2013-04, Vol.11 (4), p.502-513
• Main Authors: Gašparová, Renata, Koiš, Pavol, Lácová, Margita, Kováčová, Silvia, Boháč, Andrej
• Format: Article
• Language: English
• Subjects: Acetates; Alcohols; Biochemistry; Biological and Medical Physics; Biophysics; Chemistry; Chemistry and Materials Science; Chemistry/Food Science; Condensation; Condensing; Coumarin; Derivatives; Geochemistry; Microwave; Nucleophilic substitution; Pathways; Pyranochromenes; Rearrangement; Research Article; Synthesis
• ISSN: 1895-1066; 2391-5420; 1644-3624; 2391-5420
• DOI: 10.2478/s11532-012-0184-1

The key 3-(2-oxo-2 H -chromen-3-yl)-2-oxo-2 H ,5 H -pyrano[3,2- c ]chromen-5-yl acetates 3 were synthesized in high yields by cyclocondensation of 4-oxo-4 H -chromen-3-carbaldehydes 1 with coumarin-3-acetic acids 2 under mild conditions. The reaction pathway involves aldol condensation and subsequent intramolecular lactonization to afford 2-oxo-2 H ,5 H -pyrano[3,2-c]chromene skeleton 3 . Further treatment of acetates 3 with alcohols, water or nitrogen containing compounds led to 5-alkoxy-, 5-hydroxy- or 5-acylamino-2 H ,5 H -pyrano[3,2- c ]chromen-2-ones 4 - 6 via nucleophilic substitution of acetyloxy group at C-5. Acetates and hydroxyl derivatives 3 and 5 undergo facile rearrangement in an acid medium yielding 5-hydroxypyrano[2,3- b ]chromen-2(10a H )-ones 7 . Twelve prepared compounds were evaluated on their antineoplastic activities on 60 human tumour cell line panels in NCI USA. The obtained biological results confirmed that 3-(2-oxo-2 H -chromen-3-yl)-2 H ,5 H -pyrano[3,2- c ]chromen-2-one represents a new leading skeleton suitable for further antitumour activity study.