摘要：

Tricyclic alkaloid (-)-205B (1, Scheme 1) was isolated by Daly and co-workers in 1987 from the skin of the neotropical poisonous frog Dendrobates, and its structure was elucidated a year later by the same group. Biological studies revealed that the enantiomer of the alkaloid displays selective activity for the inhibition of the α7-nicotinic acetylcholine receptor, which has been shown to be implicated in several neurological diseases. From a structural standpoint, with an 8b-azaace-nonaphthylene ring system, (-)-205B has a more complex architecture than most indolizidine alkaloids. In 2003, Toyooka et al. reported the first total synthesis of 1 in 30 steps starting from the known (S)-6-(tert-butyldiphenylsiloxy-methyl)-piperidin-2-one. In their synthesis, two stereocon-trolled conjugate additions served to elaborate the 2,3,5,6-tetrasubstituted piperidine ring system and introduce four of the five stereocenters in the molecule. The second total synthesis of the natural product required 19 steps and was achieved in 2005 by Smith and Kim, who employed a three-component linchpin union of silyl dithianes for the straightforward construction of the indolizidine portion of the molecule. With four stereocenters in the piperidine ring, (—)-205B was an attractive target for expanding the scope of dihydropyridone reactions developed by our group. Herein, we report a concise and highly stereocontrolled asymmetric synthesis of (-)-205B.

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