Stemona alkaloid stenine

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. 

Hart s approach toward the stemona alkaloids stenine serves to illustrate a common strategy for the further transformation of the unsaturated amide (Scheme 7.28) [57]. Rearrangement of 76 followed by treatment of product 77 with iodine in aqueous THF afforded iodolactone 78, which was then converted into the natural product using the iodine substituent as a functional handle to introduce an ethyl side chain. Wipf used a similar strategy involving a selenolactoniza-tion to synthesize tuberostenine [58]. 

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). ... 

The Keck radical allylation is a representative example of a radical fragmentation reaction employing the reagent allyltributyltin in the allylation process. " The first synthesis of the Stemona alkaloid stenine by Hart in 1990 established an iodolactonization/Keck allylation (93 —> 94) sequence (Scheme 25.44) as a solution to the problem of stereoselective ethyl group installation. ... 

Allenols may be carbonylated under quite different conditions. Using Rus (CO)i 2 as the catalyst, unsaturated lactones can be synthesized efficiently." The reaction may also be extended to lactams." This cyclization, combined with an intramolecular propargylic Barbier reaction has been used in syntheses of mintlactone 4.111 from allenol 4.110 (Scheme 4.43)" " and its diastereoisomer, isomintlactone," as well as the stemona alkaloid, stemoamide 4.115 from allenol 4.113 (Scheme 4.44)," and in the skeleton of stenine." A different synthesis of stemoamide can be found in Chapter 8, Scheme 8.112. 

Stenine Type Stemona Alkaloids Occurrence and Properties. 

The antitussive activity of the aqueous and alkaloid extracts from the roots of S. tuberosa, and five isolated stenine-type alkaloids neostenine, also named isostenine (3), tuberostemonine J (6), tuberostemonine H (7), pi-bisdehydroneotuberostemonine J (12) and neotuberostemonine (13), were evaluated in a guinea pig cough model. The alkaloid extract showed much more potent activity than the aqueous extract, indicating that the Stemona alkaloids are responsible for the antitussive activity of S. tuberosa. Neotuberostemonine (13) was the most active alkaloid, followed by neostenine, also named isostenine (3), tuberostemonine H (7), and tuberostemonine J (6) (2). 

Chen C, Hart DJ. A Diels-Alder approach to Stemona alkaloids total synthesis of stenine. J. Org. Chem. 1993 58 (15) 3840-3849. 

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