An asymmetric total synthesis of the diterpenoid alkaloid hetisine is proposed. Neither hetisine nor any of its close chemical relatives has been prepared by total synthesis. An asymmetric synthesis of this compound would be an important contribution to the field of alkaloid total synthesis. The pivotal step of the proposed synthesis is an intramolecular Diels-Alder reaction of a masked o-benzoquinone to construct a highly functionalized bicyclo[2.2.2]octene. Other key steps in the synthesis plan include a Mannich-type reaction to build an azabicyclo[3.2.1]nonane core skeleton and a transannular C-H insertion of a diazoketone to establish one of the more challenging carbon-carbon bonds in the hetisine skeleton. The synthesis plan is sufficiently flexible that many of the approximately 100 members of the hetisane family of diterpenoid alkaloids could also be prepared by extension of the synthesis plan presented here. ? ?
| Dunn, Travis B; Ellis, J Michael; Kofink, Christiane C et al. (2009) Asymmetric construction of rings A-D of daphnicyclidin-type alkaloids. Org Lett 11:5658-61 |
