Total Synthesis of the Stemona Alkaloid - -Stenine

Abstracted with permission from J. Am. Chem. Soc., 1995,117, 11106 1995 American Chemical Society 

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Quite recently, a domino Diels-Alder/Prins/pinacol reaction was reported by Barriaulfs group [38]. This novel method is very reliable and efficient for the synthesis of highly functionalized bicyclo[m.n.l]alkanones. In addition, Aube and coworker [39] used a combination of a Diels-Alder and a Schmidt reaction within the total synthesis of the Stemona alkaloid stenine [40]. 

An interesting approach toward the total synthesis of the Stemona alkaloid, (-)-stenine (25), which have been used in Chinese and Japanese folk medicine as insecticides, as drugs for the treatment of respiratory diseases, via spirolactone... 

During the endgame of the total synthesis of the stemona alkaloid (-)-stenine, Y. Morimoto and co-workers utilized the Finkelstein reaction to prepare a primary alkyl iodide from a primary alkyl mesylate. The mesylate was prepared from the corresponding primary alcohol with MsCI/EtsN. The resulting primary alkyl iodide was used in the subsequent intramolecular N-alkylation to construct the final perhydroazepine C-ring of the natural product. 

The power of the intramolecular Schmidt reaction is demonstrated in the concise synthesis of the Stemona alkaloid stenine. Reaction of trimethylsilyloxy diene 79 with cyclohexenone 80 and tin(IV) tetrachloride brings about a tandem Diels-Alder/Schmidt reaction to give adducts 82 and 83 in 52% and 17% yields, respectively, with the exo addition product 83 predominating. Adduct 83 contains three rings and four stereocenters present in stenine. The intramolecular Schmidt reaction is also employed as a key step in the total syntheses of 251 F (84 to 85) and (+)-aspidospermidine (87 to 88). ... 

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