Study for Asymmetric Syntheses of Alkaloids with Nurotransmission Inhibitory Effects

以加成Pummerer反应[1，2]和羰基烯丙基化反应为关键步骤，合成了具有神经递质抑制作用的生物碱--过氢硫柳碳毒素1。在烯丙基溴化镁的作用下，乙烯基亚砜2选择性地生成了乙烯基硫化物3(90%e.E.)通过加法Pummerer反应。通过将新生成的季碳转化为(+)-麦芽内酯，确定其绝对构型为S。然后，将乙烯基硫化物3转化为醛4。钯催化4的分子内羰基芳基化反应进行了非对映选择性，得到了具有所需立体化学的5，从而同时构建了三个相邻的不对称碳中心。最后，螺环化合物5被转化为已知的中间体6。由于6通过Takahashi和同事[3]的方法经过6步得到(+)-1，(+)-1的形式合成被完成。[1]C.Iwata等，J.Chem.Soc.，Chem.Commun，1991,1408.[2]C.Iwata等，同上，1991,1049.[3]K.Takahashi等，Helv.Chim.Acta，1982，65,252.

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 [3], 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.[1] C.Iwata et al., J.Chem.Soc., Chem.Commun., 1991,1408.[2] C.Iwata et al., ibid., 1991,1049.[3] K.Takahashi et al., Helv.Chim.Acta, 1982,65,252.