Enantiospecific Synthesis Of Silphiperfolane, Basmane And Fusicoccanes

Abstract

Nature’s expertise and virtuosity in creating a phenomenal array of carbocyclic frameworks finds its full expression in the terpenoid group of natural products. The total synthesis of natural products frequently provided the impetus for great advances in organic synthesis. The thesis entitled “Enantiospecific synthesis of silphiperfolane, basmane and fusicoccanes” describes the enantiospecific total synthesis of silphiperfolanes, enantiospecific approach to a bisnorbasmane and an enantiospecific formal total synthesis of ent-fusicoauritone. In the thesis, in each chapter the compounds are sequentially numbered (bold) and references are marked sequentially as superscripts and listed at the end of the chapter. All the spectra included in the thesis were obtained by xeroxing the original NMR spectra. Silphiperfol-6-ene, is the first member of silphiperfolane sesquiterpenes, isolated in 1980 by Bohlmann et al. from Silphium perfoliatum. In 1990, Wright and coworkers reported the isolation of (6S,7R)-silphiperfolan-6-ol (wrongly assigned as (6R,7S)-silphiperfolan-6-ol) from the red algae Laurencia majuscula. Subsequently, in 1997, Wayerstahl and coworkers reported the isolation of all the four possible diastereomers (with respect to C-6 and C-7) of silphiperfolan-6-ols from the essential oil of the rhizomes of Echinops giganteus var lelyi C.D Adams. In the present thesis, enantiospecific synthesis of angular triquinanes has been described in the first chapter. To begin with, (R)-limonene was transformed into the known 6-isopropenyl-1,5-dimethylbicyclo[3.3.0]octan-3-one, which was used as the key intermediate for the construction of the angular triquinane of siliphiperfolanes. An intramolecular rhodium carbenoid insertion into the CH bond of atertiary methyl group at the ring junction of diquinane was employed as the key reaction forthe synthesis of the angular triquinane for the generation of norsilphiperfolane and norcameroonanes. The methodology has been extended to an enantiospecific total synthesis of silphiperfol-6-ene and its C-9 epimer, starting from the diquinane containing a secondary methyl group in addition to two ring junction tertiary methyl groups. In the process, it was also observed a competitive intramolecular insertion of the rhodium carbenoid into the γ- and β-CH bonds leading to the generation of cyclopentanone and cyclobutanones. Subsequently, the sequence has been modified and enantiospecific first total syntheses of(6S,7R)- silphiperfolan-6-ol and (6R,7S)-silphiperfolan-6-ol have been accomplished. In 1983, Wahlberg and coworkers reported the isolation of the diterpenoid 7,8-epoxy-4-basman-6-one, containing an interesting 5-8-5 tricyclic system, from the volatile neutral portion of the diethyl ether extract of sun-cured leaves of greek tobacco (serres). In 1994, Becker et al. reported the isolation of fusicoauritone from the liverwort Anastrophyllum auritum collected in Ecuador. In the second chapter, enantiospecific synthesis of the 5-8-5 ring system of bisnorbasmane and an enantiospecific formal total synthesis of fusicoauritone have been described, starting from the readily available monoterpene (R)-limonene. RCM reaction of a decadiene was employed as the key reaction for the generation of the AB ring system of fusicoccane and basmanes. An intramolecular rhodium carbenoid CH insertion of a diazoketone was utilized for the construction of the C-ring of basmanes. Subsequently, an enantiospecific formal total synthesis of fusicoauritone has been accomplished. Two RCM reactions were employed as the key reactions for the construction of the eight- and five membered rings B and C, respectively, of fusicoccanes.