Azatricyclic core

J.D. White et al. reported the total synthesis of ( )-ibogamine via the catalytic asymmetric Diels-Alder reaction of benzoquinone. The azatricyclic framework of the molecule was established by converting the bicyclic ketone to the anti oxime and then subjecting it to a Beckmann rearrangement in the presence of p-toluenesulfonyl chloride to afford the 7-membered lactam. Elaboration of this lactam into the azatricyclic core of ibogamine and later to the natural product itself was accomplished in a few additional steps. 

Four total syntheses of FR901483 have been reported so far the enantiocontrolled approaches of Snider [2], Sorensen [5], and Ciufolini [6], and Funk s synthesis in the racemic series [7]. Furthermore, Brummond has communicated a partial total synthesis [8] and Wardrop reported a formal synthesis of the desmethylamino analog, which had been described by Snider [9,10]. Additionally, Kibayashi and Bonjoch and co-workers have reported other synthetic entries to the azatricyclic core of FR901483, which has also been reported by Brummond in her initial studies [11-14], An overview of FR901483 synthetic studies is outlined in Table 1. 

Azatricyclic Core Kibayashi (1997) II 2-azabicyclononane C(4>N(5) reductive amination ( )... 

In 2014, an intramolecular atom transfer radical cyclisation (ATRC) between a trichloroacetamide and an anisole or enol acetate moiety was applied to the synthesis of highly functionalized 2-azaspiro[4.5]decanes or morphan compounds, respectively, using the second-generation Grubbs catalyst 20. The procedure was further employed to construct the azatricyclic framework of the immunosuppressant FR901483 by the elaboration of its azatricyclic core [eqn (7.15)]. 

---