Synthesis of Biologically Active Compounds by Means of an Intramolecular Polar Cycloaddition of Thionium Ions

1. 为了确定硫离子极性环加成的合成效用，我们首先研究了[4^++2]型反应的分子间版本。因此，当间甲基硫甲基氯在刘易斯酸存在下与各种1-甲基和1.2-二甲基- 1-环戊烯反应时，可以得到收率较高的环戊烷融合硫代铬衍生物。这些产物转化为芳族倍半萜类化合物，如铜萜烯、α -铜萜烯、β -铜萜烯和乙酸甲乙酯。利用上述[4^++2]反应的分子内版本合成鬼臼毒素衍生物已有几次尝试，但都失败了。然后，作为一种替代途径，我们检测了(Z)- α -苄基- β -（邻溴苄基）- γ -内酯的Heck反应，该反应由胡椒醛、γ -巴豆内酯和3,4,5 -三甲氧基苯甲醛经过10步制备，得到了产率很高的γ -apopicropodophyllin。由于该产物已转化为鬼臼毒素，因此整个反应顺序意味着鬼臼毒素的正式全合成。由1-甲基亚砜基-5.7-辛二烯-2- 1衍生的硫离子在分子内[2^++4]极性环加成，然后对产物进行碱基处理，得到1-甲基硫基-6-乙烯基双环-[3.1.0]己烷-2- 1，其转化为前列腺素衍生物的研究正在深入进行。

1. In order to establish the synthetic utility of the polar cycloaddition of thionium ions, we first examined an intermolecular version of the [4^++2] type reaction. Thus, when m-tolylthiomethyl chloride was allowed to react with various 1-methyl- and 1.2-dimethl-l-cyclopentenes in the presence of Lewis acid, the cyclopentane fused thiochromans derivatives were obtained in good yields. These products were transformed into the aromatic sesquiterpenes such as cuparene, alpha-cuparenone, beta-cuparenone, and tochuinyl acetate.2. Several sttempts have been made to synthesize podophyllotoxin derivatives by using the intramolecular version of the above [4^++2] reaction, but failed. Then, as an alternate route to podophyllotoxins, we examined the Heck reaction of (Z)-alpha-benzylidene- beta-(o-bromobenzyl)gamma-lactone, prepared from piperonal, gamma-crotonolactone, and 3, 4, 5-trimethoxybenzaldehyde via 10 steps : this gave gamma-apopicropodophyllin in good yield. Since this product has already been converted into podophyllotoxin, the whole sequence of the reactions means the formal total synthesis of podophyllotoxin.3. The intramolecular [2^++4] polar cycloaddition of the thionium ion derived from 1-methylsulfinyl-5.7-octadiene-2-one followed by base-treatment of the resultant product gave 1-methylthio-6-vinylbicyclo [3.1.0] hexane-2-one, whose transformation into prostaglandin derivatives is under intense investigation.