Fremy’s Salt-Mediated Oxidative Addition. A New Approach in the Total Synthesis of Naturally Dipetalolactone and Its Immunomodulatory Activity

Abstract: The structure of the natural dipyranocoumarin dipetalolactone has been confirmed by an unambiguous synthetic route from resorcinol. This sequence was initiated by a pyran ring formation step which introduced the 3-chloro-3-methylbut-1-yne moiety. Then, the expected product undergoes a Fremy’s salt-meditated oxidative addition followed by ring closure to yield dipetalolactone. Dipetalolactone was also found to have immunological activity in a mouse carcinoma S180-bearing mice cell line. Keywords: coumarins; dipyranocoumarin; dipetalolactone; Fremy’s salt 1. Introduction Dipetalolactone is a natural product dipyranocoumarin isolated from different plants like Zanthoxylum dipetalum , Metrodorea flavido and Diplolaene mollis (Rutaceae) [1]. The dipyranocoumarins, a group of natural products from several tropical plants of the genus Calophyllum are characterized by coumarin, chromene and chromane ring systems [2]. Biologically, dipyranocoumarins are very useful and many of them have exhibited anti HIV, antibacterial, antitumor, vasodilator (in coronary vessels) and anticoagulant activities [3]. It was long noted that