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

1.为了确定硫离子的极性环加成反应的合成实用性，我们首先考察了[4^++2]型反应的一个分子间版本。因此，当间甲苯基硫代甲基氯在Lewis酸存在下与各种1-甲基和1，2-二甲基-L-环戊烯反应时，以较高的产率得到了环戊烷稠合的硫色满衍生物。这些产物转化为芳香族倍半萜，如铜烯、α-铜烯酮、β-铜烯酮和生育基乙酸酯。利用上述[4^++2]反应的分子内版本曾多次尝试合成鬼臼毒素衍生物，但均以失败告终。然后，作为鬼臼毒素的替代路线，我们研究了以胡椒醛、γ-巴豆内酯和3，4，5-三甲氧基苯甲醛为原料制备的(Z)-α-亚苄基-β-(邻溴苯基)伽马内酯与3，4，5-三甲氧基苯甲醛的Heck反应。由于该产物已经转化为鬼臼毒素，因此整个反应过程意味着鬼臼毒素的正式全合成。由1-甲基亚磺基-5.7-辛二烯-2-酮衍生的硫离子经分子内[2++4]极性环加成，再经碱处理得到1-甲硫基-6-乙烯基双环[3.1.0]己烷-2-酮，其转化为前列腺素衍生物的研究正在进行中。

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.