Chemistry of Phosphorus Ylides. Part 37. The Reaction of Phosphonium Ylides with Indoles and Naphthofurans. Synthesis of Phosphanylidenes, Pyrans, Cyclobutenes, and Pyridazine as Antitumor Agents

The reaction of the stabilized phosphonium ylides 2a, 2b with indolinones 1a, 1b and naphthofuranone 13 afforded the corresponding propylidene and ethylidene derivatives 4a, 4b, 4c, 4d and 14a, 14b. On the other hand, the active phosphacumulenes 5a, 5b react with compounds 4a, 4b, 4c, 4d by [4+2]-cycloaddition to give the stable phosphanylidene indole pyranones 6a, 6b, 6c, 6d, 6e, 6f, 6g, 6h. Although compounds 14a, 14b afforded the naphthofuropyrans 16a, 16b, 16c, 16d and triphenylphosphane. Moreover, the phosphallene ylide 7 react with compounds 4a, 4b, 4c, 4d and 14a, 14b to give phosphanylidenecyclobuteneindoline 9a, 9b, 9c, 9d and naphthalenones 18a, 18b, respectively. In addition, the naphthofuropyridazine 21 was obtained from the reaction of the hydrazone 19 and the phosphacumulene 5a. The antitumor activity of some of the new compounds was evaluated, in vitro, against colon and hepatocellular carcinoma cell lines. They showed values closed to that recorded by the reference drug Doxorubicin.