A new synthesis of rotenoids. Application to 9-demethylmunduserone, mundeserone, rotenonic acid, dalpanol, and rotenone

Abstract

A new synthesis of rotenoids, which involves reaction of a 2′-hydroxyisoflavone with dimethylsulphoxonium methylide followed by rearrangement of the vinylcoumaranone formed, is described. This supplies C-6 by a one carbon entity, as in nature, and unlike other methods attains the correct oxidation level of the B/C ring system without further reduction–oxidation procedures. In illustration, (±)-isorotenone (13) is prepared from isoderritol (11a), and (–)-rotenone (1) from derritol. Total synthesis of the biosynthetically important (±)-9-demethylmunduserone (16), and the natural rotenoid (±)-munduserone (20) is reported using Wanzlick synthesis for the necessary flavonoids. (±)-9-Demethylmunduserone can be dimethylallylated at C-8 to give (±)-rot-2′-enonic acid. Hydrogenation of (–)-rotenone to (–)-rot-2′-enonic acid (17a) and mutarotenone to (±)-rot-2′-enonic acid is re-examined and found to involve two types of 1,2- as well as 1,4-(1′–7′)reduction. Following the lines of the biosynthetic pathway, (–)-rot-2′-enonic acid is epoxidised and converted into (–)-dalpanol (18), the apparent immediate precursor of (–)-rotenone in nature. Apart from resolution of (±)-rot-2′-enonic acid, this constitutes a formal total synthesis of (–)-dalpanol.