Securinine alkaloids synthesis

Reduction of norsecurinine with zinc and suKuric acid gave the oily lactam 169 which was extremely unstable and thus was immediately converted into the hexahydropyrrolo[2,l-a]isoquinoUne 170. This rearrangement was predicted from the previous results of the same reaction effected on securinine and related alkaloids e.g., Section II, A, 1) and was confirmed by synthesis of compound 170 from the pyrrolidinone 171 in two steps. Thus the skeletal structure 164 of norsecurinine as originally proposed (60) was fully confirmed (62). 

An alternative partial synthesis of securinine was also developed by Horii and co-workers (65, 69). The unconjugated lactone 12 available from a key degradation of the alkaloid (Scheme 1) gave upon bromina-tion a 71% yield of the dibromide 195 which upon basic treatment yielded natural securinine (27) in 15% yield. It may be envisaged that this short route could provide a new relay stage for the total synthesis of the alkaloid. 

Securinine (1) represents the iconic target for total synthesis in this series and up today (June 2014), a total of 12 total syntheses have been reported. Indeed, the first syntheses were not stereoselective and gave access to the pair securiiiine/virosecurinine as a racemic mixture, second generation syntheses allowed the preparation of this alkaloid as a pure enantiomer. Moreover, due to the existence of four possible stereoisomen, sfight modifications of an initial strategy can furnish the others isomers. 

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