Synthesis of 6-hydroxy-2,3,9-trimethoxy-[1]-benzopyrano [3,4-b] [1] benzopyran-12(6H)-one

Abstract

The total synthesis of dehydrorotenoid (1), was successfully achieved in three steps through an intramolecular aldol reaction of the corresponding 1,2-diaryl diketone (19) as a key intermediate. The corresponding 1,2-diaryl diketone was easily accessed via the ruthenium-catalyzed oxidation of diarylacetylene which was obtained from Sonogashira coupling between monoaryl substituted acetylene and aryl iodide. Treatment of 1,2-diaryl diketone with L-proline induced a selective intramolecular aldol reaction, forming the desired benzopyranone without a byproduct benzofuran. Finally, the target dehydrorotenoid was accomplished in 45% overall yield by deprotection and dehydration reactions, respectively. The synthesized dehydrorotenoid (1) and intermediate compounds were evaluated for their biological activities. The results illustrate that compound 1 is inactive, while compound 154 shows activity inhibition of NCI-H187, KB and MCF7 cancer cell lines. However this compound is toxicant to normal cells. Moreover, compound 169, 176a, 176d, 177b, and 177e have been found to potently inhibit the SW620, BT474, KATO-III, Hep-G2, CHAGA, and CH-LIVER cancer cell lines. Even the synthesized dehydrorotenoid (1), target molecule, does not show the expected biological activity but this synthetic methodology provides a very useful procedure for synthesis of the most isoflavanoid, rotenoid and dehydrorotenoid core structure. Therefore, this methodology is valuable for the further study of structure-activity relationship