|Budget Amount *help
¥2,000,000 (Direct Cost: ¥2,000,000)
Fiscal Year 1995: ¥700,000 (Direct Cost: ¥700,000)
Fiscal Year 1994: ¥1,300,000 (Direct Cost: ¥1,300,000)
Formal synthesis of perhydrohistrioniocotoxin 1, an alkaloid with the inhibitory effect against neurotransmission, was accomplished using an additive Pummerer reaction [1,2] and a carbonyl allylation reaction as crucial steps.
On treatment with allylmagnesium bromide, the vinylic sulfoxide 2 gave selectively the vinylic sulfide 3 (90% e.e.) by additive Pummerer reaction. The absolute configuration of the newly formed quaternary carbon was determined as S by converting it into (+) -malyngolide. Then, the vinylic sulfide 3 was converted into the aldehyde 4. Palladium-catalyzed intramolecular carbonyl aflylation of 4 proceeded diastereoselectively to afford 5 with the desired stereochemistry, thereby constructing the three contiguous asymmetric carbon centers simultaneously. Finally, the spiro compound 5 was converted into the known intermediate 6. Since 6 leads to (+) -1 in 6 steps by the method of Takahashi and coworkers , a formal synthesis of (+) -1 was accomplished. This synthetic route may be useful for the syntheses of histrionicotoxin and congeners and for the research on structure-activity relationship.
 C.Iwata et al., J.Chem.Soc., Chem.Commun., 1991,1408.
 C.Iwata et al., ibid., 1991,1049.
 K.Takahashi et al., Helv.Chim.Acta, 1982,65,252.