A Development of New method for the Synthesis of Chiral Cyclobutanones-A Synthetic Approach to Trichothecane Type of Macrolides

手性环丁酮合成新方法的开发——单端孢烷型大环内酯类的合成途径

• 批准号: 06672086
• 负责人: NEMOTO Hideo
• 金额: $ 1.34万
• 依托单位: TOHOKU 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: 1994
• 资助国家: 日本
• 起止时间: 1994 至 1995
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-06672086/
• 关键词: Cyclopropylidene; Asymmetric Epoxidation; Asymmetric Dihydroxylation; Concerted 1,2-Rearrangenmet; Chiral Cyclobutanone; 協奏的1,2転位反応; シクロプロピチデン; 不斉エポシキ化反応

Cyclobutanones consitute the basic structure of many natural products and are important intermediates in the synthesis of a wide range of natural products and other complex organic molecules. They are most often synthesized by [2+2] cycloaddition reactions between ketenes and olefins, and much effort hes been devoted to asymmetric induction in this cycloaddition process. In contrast, the studies on the asymmetric induction in the ring expansion reaction of cyclopropane rings to form cyclobutanes have been limited. We were intrigued by the possibility that the Katsuki-Sharpless asymmetric epoxidation of the cyclopropylidene alcohol might give the very labile chiral hydroxyoxaspiropentanes as initial products and then rearrange to chiral cyclobutanones in an enantiospecific manner under the reaction conditions. We therefore examined the Katsuki-Sharpless asymmetric epoxidation of cyclopropylidene alchols, which led us to develop the concise and highly enantioselective method for the synt … More hesis of chiral cyclobutanones. In the similar manner, the chiral diols derived by the asymmetric dihydroxylation of the cyclopropylidenes were found to be rearranged in enantiospecific manner to the optically active cyclobutanones via the cyclic sulfates. Based on these findings in 1994, we have been involved in the total synthesis of trichothecane type of sesquiterpenes, because the members of this class exhibit significant biological activities such as antifungal, antibacterial, antiviral, and insecticidal properties and also some of this family inhibit the growth of tumor cells. Then, we succeeded in the development of the efficient synthesis of A-ring aromatic trichothecanes, such as (2S,5S)-(-)-2-methyl-15-nor-6,8,10,12-trichothecatetraene, (-)-debromofiliformin, (-)-filiformin, (2R,5S)-15-nor-6,8,10,12-trichothecatetraene, (2R,5R,12S)-15-nor-6,8,10-trichothecatriene-12,13-diol, (2R,5R,12S)-12,13-epoxy-15-nor-6,8,10-trichothecatriene, and (2R,5R,12S)-12,13-dimethylmethylenedioxy-15-nor-6,8,10-trichothecatriene, in 1995. Less

环丁酮构成了许多天然产物的基本结构，是合成多种天然产物和其他复杂有机分子的重要中间体。它们通常是由烯酮和烯烃之间的[2+2]环加成反应合成的，在这个环加成过程中，人们花了很大的精力来不对称诱导。相比之下，对环丙烷环扩环反应中不对称诱导生成环丁烷的研究相对较少。我们感兴趣的是，在反应条件下，环丙叉醇的Katsuki-Sharless不对称环氧化反应可能会得到非常不稳定的手性羟基氧杂环戊烷，然后以对映异构体的方式重排成手性环丁酮。因此，我们研究了环丙叉醇的Katsuki-Sharpless不对称环氧化反应，这使我们开发了合成…的简明和高度对映选择性的方法。更多的手性环丁酮。以类似的方式，通过环硫酸酯将环丙叉烯不对称双羟基化得到的手性二醇以对映异构化的方式重排成光学活性环丁酮。基于1994年的这些发现，我们参与了三环乙烷型倍半萜的全合成，因为这类成员具有显著的生物活性，如抗真菌、抗菌、抗病毒和杀虫性能，并且该家族中的一些成员还抑制肿瘤细胞的生长。在此基础上，我们成功地合成了(2S，5S)-(-)-2-methyl-15-nor-6，8，10，12-trichothecatetraene，(-)-脱溴异氰酸酯、(-)-异氰酸酯、(2R，5S)-15-或-6，8，10，12-三氯环己烷、(2R，5R，12S)-15-nor-6，8，10-trichothecatriene-12，13-diol，(2R，5R，12S)-12，13-epoxy-15-nor-6，8，10-trichothecatriene，和(2R，5R，12S)-12，13-dimethylmethylenedioxy-15-nor-6，8，10-trichothecatriene，于1995年提出。较少

项目成果

根本英雄: "Tandem Ring Expansion and Insertion of Alknic Cyclobutanols Mediated by Palladium--A Novel Approach to Bicyclo〔4.3.0〕nonane Systems." Tetrahedron. 50. 10391-10396 (1994)

Hideo Nemoto：“钯介导的串联环膨胀和插入 - 双环 [4.3.0] 壬烷系统的新方法”。50。10391-10396 (1994)。

根本秀雄: "A Highly Enantiocontrolled Strategy for the Synthesis of Benzylic Quaternary Carbon Centers. A Formal Total Synthesis of (-)-Mesembrine" J. Org. Chem.60. 6785-6790 (1995)

Hideo Nemoto：“用于合成苄基季碳中心的高度对映体控制策略。(-)-Mesembrine 的正式全合成”J. Org. 6785-6790 (1995)。

Hideo Nemoto: "The First Example of Asymmetric Dihydroxylation of Cyclopropylidene Derivatives-An Enantioenriched Formal Total Synthesis of (-)-Filiformin" Tetrahedron Lett. 36. 1055-1058 (1995)

Hideo Nemoto：“环丙叉衍生物不对称二羟基化的第一个例子 - (-)-丝状蛋白的对映体富集正式全合成”四面体快报。

根本英雄: "A Remarkable Substituent Effect on the Enantioselectivity of Tandem Asymmetric Epoxidation and Enantiospecific Ring Expansion of Cyclopropylidene Alcohols : A New Enantiocontrolled Synthesis of(-) -Debromoaplysin and(-) -Aplysin." J. Org. Chem.59.

Hideo Nemoto：“取代基对环丙叉醇的串联不对称环氧化和对映特异性环扩张的显着影响：(-)-Debromoaplysin 和(-)-Aplysin 的新对映体控制合成”J. Org.59。

根本英雄: "An Efficient Route to Chiral Benzooxabicyclo〔3.2.1〕octane Ring System--The First Enantiocontrolled Total Synthesis of(-)-Filiformin." Heterocycles. 39. 467-470 (1994)

Hideo Nemoto：“手性苯并氧杂双环 [3.2.1] 辛烷环系统的有效途径——(-)-丝状杂环的首次对映控制全合成。”39. 467-470 (1994)