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Synthesis and Antitumor Activity of Combretastatin D-4

2008; Elsevier BV; Volume: 75; Issue: 2 Linguagem: Inglês

10.3987/com-07-11221

1881-0942

Shigeru Nishiyama, Kanako Uno, Takamasa Tanabe, Takahisa Ogamino, Ryoko Okada, Masaya Imoto,

Natural product bioactivities and synthesis

Combretastatin D-4 1 was synthesized using electrochemical dimerization of phenols as the key step.Anodic oxidation of bromochloro-phenol 7 provided the corresponding diaryl ether 8. Manipulation of the two hydroxyl groups differenciated, provided the seco-acid, which on Mitsunobu reaction gave the target molecule.Its biological assay showed new potent inhibitory activity against cellular proliferation of human HT-29 colon carcinoma cells.A family of cyclic diarylheptanoids, such as galeon, 1 pterocarine, 2 and combretastatins, 3 exhibit a wide range of biological activity, such as antitumor, antibacterial, and antiplasmodial activities.Combined with these attractive activities, their structures often have a relatively simple structure, making them promising leads to new drugs.A number of synthetic approaches to these natural products, have been reported.Among them, construction of the diaryl ether 4 has generally been attained by the Ullmann and S N Ar protocols, and total synthesis of galeon and pterocarine was recently accomplished by the former. 5ainst such back ground, we have independently developed the phenolic oxidation methodology by thallium(III) salts.