Development of New Skeletal Transformations of Polycyclic Methylenecyclobutyl Ketones and Their Application

多环亚甲基环丁基酮新骨架转化的研究进展及其应用

• 批准号: 09650959
• 负责人: KAKIUCHI Kiyomi
• 金额: $ 2.11万
• 依托单位: NARA INSTITUTE OF SCIENCE AND TECHNOLOGY
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 1997
• 资助国家: 日本
• 起止时间: 1997 至 1998
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-09650959/
• 关键词: polycyclic compounds; methylenecyclobutyl ketone; skeletal transformations; pentalenene; mediterraneol B; taxol; acid catalysts; bridgehead substituents; テルペン系天然物; ラルペン系天然物

In this research, we have carried out the systematic investigation of skeletal rearrangements of polycyclic methylenecyclobutyl ketones prepared easily by photocycloaddition of corresponding cyclic enones to allene to develop the new method for construction of functional and useful polycyclic compounds. Furthermore, in order to exemplify the utility of the method, we have also done the synthetic study of some terpenoids. Reactions of 6-4-fused ketones bearing alkyl substituents at the C6 with acids such as H2S0_4, p-TsOH, CF_3SO_3H, BF_3 OEt2, FeCl_3, AlCl_3, TiCl_4, and BCl_3 gave various kinds of products. In the cases of the methyl and ethyl derivatives, cyclooctenones were obtained mainly using TiCl_4 and BCl_3, while cyclohexenones were major products using the other acids. In the cases of isopropyl and tert-butyl derivatives, however, bicyclo[4.2.1]nonanones were formed in good yields with TiCl_4 and BCl_3, and bicyclo[4.3.0]nonanones were produced with the other acids. The difference of the reactivity toward acids may be explained by the affinity of the acid to the carbonyl group of the substrate prefer to the exo-methylene moiety. Also, the products can be divided into two groups by acid used, and the difference may be attributed to the stability of the carbocation intermediates dependent on the bridgehead substituents. Utilizing this rearrangement protocol as a key step, total syntheses of (*)-pentalenene and (*)-tetramethylmediterraneol B have been achieved. Furthermore, the synthetic study on the anticancer terpenoid taxol is in progress.

本研究通过环烯酮与丙二烯的光环化加成反应，系统地研究了多环亚甲基环丁基酮的骨架重排，为构建功能性多环化合物提供了新的方法。此外，为了举例说明该方法的实用性，我们还对一些萜类化合物进行了合成研究。C_6上带有烷基取代基的6-4-稠合酮与H_2SO_4、p-TsOH、CF_3SO_3H、BF_3、OEt_2、FeCl_3、AlCl_3、TiCl_4和BCl_3等酸反应，得到各种产物。在甲基和乙基衍生物的情况下，环辛烯酮主要由TiCl_4和BCl_3生成，而环己烯酮则主要由其他酸生成。在异丙基和叔丁基衍生物的情况下，与TiCl_4和BCl_3反应生成双环[4.2.1]壬酮的产率较高，与其它酸反应生成双环[4.3.0]壬酮。对酸的反应性的差异可以通过酸对底物的羰基的亲和力优先于外亚甲基部分来解释。此外，产物可以分为两组所使用的酸，和差异可能归因于依赖于桥头取代基的碳阳离子中间体的稳定性。以该重排反应为关键步骤，实现了（*）-并环戊二烯和（*）-四甲基间苯二酚B的全合成。此外，抗癌萜类化合物紫杉醇的合成研究也在进行中。