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

通过锍离子的分子内极性环加成合成生物活性化合物

• 批准号: 02670967
• 负责人: ISHIBASHI Hiroyuki
• 金额: $ 1.41万
• 依托单位: Kyoto Pharmaceutical University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for General Scientific Research (C)
• 财政年份: 1990
• 资助国家: 日本
• 起止时间: 1990 至 1991
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-02670967/
• 关键词: Thionium Ion; alpha-Chlorosulfide; Polar Cycloaddition; Thiochroman; Cuparene; Aromatic Sesquiterpene; Podophyllotoxin; Heck Reaction; スルホキシド; ラジカル環化反応; αークパレノン; βークパレノン; トチュイニルアセテ-ト

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.

1.为了确定硫鎓离子极性环加成的合成效用，我们首先研究了[4^++2]型反应的分子间形式。因此，当间甲硫基氯甲烷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，以良好的产率得到环戊烷稠合的硫代苯并二氢吡喃衍生物。这些产物被转化为芳香族倍半萜类化合物，如cuparene、α-cuparenone、β-cuparenone和醋酸托川酯.利用上述[4^++2]反应的分子内形式，人们曾尝试合成鬼臼毒素衍生物，但均未成功。然后，作为鬼臼毒素的替代路线，我们研究了由胡椒醛、γ-巴豆内酯和3，4，5-三甲氧基苯甲醛经10步制备的（Z）-α-亚苄基-β-（邻溴苄基）γ-内酯的Heck反应：这以良好的产率得到γ-苦鬼臼脂素。由于该产物已经转化为鬼臼毒素，因此整个反应序列意味着鬼臼毒素的正式全合成。由1-甲基亚磺酰基-5.7-辛-2-酮衍生的硫鎓离子经分子内[2^++4]极性环加成反应，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深入进行中。

项目成果

Hiroshi Nakatani: "Synthesis of Thiochromans by Means of a [4^++2]Polar Cycloaddition of mーTolylthiomethyl Chloride with Substituted Alkenes:A Simple Synthesis of(±)ーCuparene and Related Sesquiterpenoids" Chem.Pharm.Bull.38(5). 1233-1237 (1990)

Hiroshi Nakatani：“通过间甲苯基硫甲基氯与取代烯烃的[4^++2]极性环加成合成硫色满：(±)ーCuparene和相关倍半萜的简单合成”Chem.Pharm.Bull.38（ 5). 1233-1237 (1990)。

Hiroshi Nakatani: "Synthesis of Thiochromans by Means of a [4^++2] Polar Cycloaddition of m-Tolylthiomethyl Chloride with Substituted Alkenes : A Simple Synthesis of (<plus-minus>)-Cuparene and Related Sesquiterpenoids" Chem. Pharm. Bull.38(5). 1233-1237

Hiroshi Nakatani：“通过间甲苯基硫代甲基氯与取代烯烃的 [4^2] 极性环加成合成硫苯并二氢吡喃：(<plus-minus>)-Cuparene 和相关倍半萜的简单合成” Chem.

Hiroyuki Ishibashi: "A Short Synthesis of (<plus-minus>)-Cupare " J. Chem. Soc., Chem. Commun.1988(12). 827-828 (1988)

Hiroyuki Ishibashi：“(<plus-minus>)-Cupare 的简短合成” J. Chem。

Hiroyuki Ishibashi: "Recent Advances in the Carbon-Carbon Bond Forming Reactions with alpha-Chlorosulfides" Yakugaku Zasshi. 112(4). 215-228 (1992)

Hiroyuki Ishibashi：“α-氯硫化物碳-碳键形成反应的最新进展”Yakugaku Zasshi。

Hiroyuki Ishibashi: "Recent Advances in the Carbon-Carbon Bond Forming Reactions with α-Chlorosulfides" Yakugaku Zasshi. 112. 215-228 (1992)

Hiroyuki Ishibashi：“α-氯硫化物碳-碳键形成反应的最新进展”Yakugaku Zasshi。112. 215-228 (1992)