Stereocontrolled total synthesis of the Stemona alkaloid (-)-stenine

The Stemona alkaloid stenine (1), isolated from Stemona tuberosa of physiol ogically active stemonaceous plants, possesses the structurally novel and u nique azepinoindole skeleton (B,C,D-ring system). We have achieved the asym metric total synthesis of (-)-stenine (1). starting from 1,5-pentanediol (1 0). The key features are an intramolecular diastereoselective Diels-Alder r eaction of the (E,E,E) triene 6, prepared in a convergent fashion from thre e components-dienyl chloride 7, dithiane 8, and chiral phosphonate 9- and e fficient construction of the tricyclic A,B,D-ring system 29 through thermod ynamically controlled regioselective enolization of the bicyclic ketone 25. In this article. we describe in detail the highly stereocontrolled total s ynthesis of (-)-stenine (1). These results should be useful for the asymmet ric total synthesis of another, more complex, molecule: tuberostemonine (2) , the synthesis of which has never been reported.