Amaryllidaceae alkaloids 7-deoxypancratistatin

The Amaryllidaceae alkaloid 7-deoxypancratistatin 21 has potent antiviral activity. A challenge in the assembly of 21 is that the ring fusion is trans, less stable than the corresponding cis diastereomer. The s mthesis of 21 J. Org. Chem. 2007, 72, 2570) by Albert Padwa of Emory University started with 17, the preparation of which by the combination 15 and 16 he had previously reported in the course of his s mthesis of lycoricidine OHL December 11, 2006). Ester 17 had the desired trans ring fusion, but with an angular ester substituent that had to be removed. 

Several members of the Amaryllidaceae family of alkaloids display pronounced biological activities, and some Amaryllidaceae plants have played an important role in traditional herbal medicine for the treatment of various ailments. The most prominent examples of Amaryllidaceae alkaloids of biological relevance are narciclasine (55) and its congeners (pancratistatin and 7-deoxypancratistatin) and galantamine (62) (also commonly spelled galanthamine). These natural products also find application in modem medicine, and in this respect, pancratistatin is used in clinical... 

Deoxypancratistatin Keck, 1998 In 1995, Keck reported his first synthesis of 7-deoxypancratistatin (298) with a radical cyclization as key step [178]. A few years later, a second-generation synthesis of this important Amaryllidaceae constituent was reported [173]. The route, outlined in Schemes 12.50 and 12.51, started from inexpensive and commercially available L-gulonolactone (289) and featured a highly efficient radical cyclization cascade, which established two ring systems of the natural product. This radical cyclization protocol is quite unique in the preparation of Amaryllidaceae alkaloids and constitutes an interesting alternative to commonly employed coupling protocols. 

---