Neurotoxins pumiliotoxin

Within a total synthesis of the neurotoxin (-)-pumiliotoxin C [52], Minnaard, Fer-inga and coworkers used a domino Heck/Tsuji-Trost reaction of 6/1-93 and 6/1-94 to give the perhydroquinoline 6/1-95 in 26% yield after hydrogenation [53] (Scheme 6/1.24). 

Addition of this homoenolate to the ketone 23, a single enantiomer derived from natural proline, gives the tertiary alcohol 24 with high stereoselectivity.7 Removal of the Cbz protecting group leads to spontaneous cyclisation to give 25, an intermediate on the way to the neurotoxin pumiliotoxin 251D 26. 

As part of the total synthesis of the neurotoxin (-(-pumiliotoxin C [69], Minnaard and coworkers [70] used a domino Mizoroki-Heck/Tsuji-Trost reaction as the key step to prepare the perhydroquinoline 124 in 26% yield from 122 and 123 after hydrogenation (Scheme 8.31). Similarly, acyclic tosyl amides with vinyl bromides have been used to give the corresponding lactams in 49-82% yield [71]. 

An interesting way of enolate trapping has been realized by Feringa and coworkers under the form of a palladium-catalyzed allylic alkylation [210]. By applying this consecutive reaction to cyclohexenone, the alkene 427 was accessible in 96% enantiomeric excess in the trans-diastereomer that formed predominantly [211]. The product was carried on in a total synthesis of the potent neurotoxin (-)-pumiliotoxin C (Scheme 5.109) [210c]. 

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