Pumiliotoxin diastereomer

For alkenyl nitrile oxides having the alkene in a cyclic structure, such as compound 141, high diastereoselectivities can be obtained (Scheme 12.47). Compound 141 is formed in situ, and undergoes a spontaneous cyclization to furnish 142 as the sole diastereomer. Toyota et al. (239) used the tricyclic isoxazoline 143 in the synthesis of (+)-pumiliotoxin C. 

Consists of two diastereomers, poss. allylic rearr. prods, of Pumiliotoxin A, P-02169. Trace alkaloid from skin extracts of the Madagascan frogs Mantella aurantiaca and M. crocea. Minor constit. of M. viridis. 

The next synthesis uses a chiral auxiliary approach in which the auxiliary is not sacrificed. The synthesis begins with anthranihc acid derivative 157. A potassium-ammonia reduction provided a mixture of diastereomers 158 and 159. A directed hydrogenation of the major diastereomer (159), using Crabtree s cationic iridium catalyst, provided 160. This material was moved forward to pumiliotoxin-C through intermediates we encountered in the Overman approach (compare the substitution pattern and relative stereochemistry of 160 with 131 on Pumihotoxin-3). 

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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