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

环丁酮是许多天然产物的基本结构，也是合成许多天然产物和其它复杂有机分子的重要中间体。它们通常通过烯酮与烯烃的[2+2]环加成反应合成，并且在该环加成过程中的不对称诱导方面已经做了大量的工作。相比之下，环丙烷扩环生成环丁烷反应中的不对称诱导研究则较为有限。Katsuki-Sharpless不对称环氧化环亚丙基醇的可能性，我们很感兴趣的是，可能会得到非常不稳定的手性羟基氧杂螺戊烷作为初始产品，然后重排手性环丁酮在反应条件下的对映体特异性的方式。因此，我们研究了Katsuki-Sharpless环亚丙基醇的不对称环氧化反应，从而发展了一种简洁、高对映选择性的合成环亚丙基醇的方法。 ...更多信息 手性环丁酮的合成。以类似的方式，由环亚丙基的不对称二羟基化衍生的手性二醇被发现通过环状硫酸酯以对映体特异性的方式重排为光学活性的环丁酮。基于1994年的这些发现，我们一直参与了倍半萜烷类化合物的全合成，因为该类化合物具有显著的生物活性，如抗真菌、抗细菌、抗病毒和杀虫特性，并且该家族的一些化合物还抑制肿瘤细胞的生长。在此基础上，我们成功地开发了（2S，5S）-（-）-2-甲基-15-去甲-6，8，10，12-炔诺酮、（-）-脱溴菲咯啉、（-）-菲咯啉、（2 R，5S）-15-去甲-6，8，10，12-炔诺酮、（2 R，5 R，12 S）-15-去甲-6，8，10-三烯-12，13-二醇、（2 R，5 R，12 S）-12，13-环氧-15-去甲-6，8，10-三烯和（2 R，5 R，12 S）-12，13-二甲基亚甲二氧基-15-去甲-6，8，10-三烯，1995年。少

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