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

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，在这种环加成过程中，人们对不对称诱导进行了大量的研究。而对于环丙烷环展开反应中不对称诱导生成环丁烷的研究则比较有限。我们对环丙醇的Katsuki-Sharpless不对称环氧化反应可能产生非常不稳定的手性羟基草戊烷作为初始产物，然后在反应条件下以对映特异性的方式重排成手性环丁酮的可能性很感兴趣。因此，我们研究了环丙醇的Katsuki-Sharpless不对称环氧化反应，从而开发了一种简洁、高对映选择性的手性环丁酮合成方法。同样地，由环丙烯的不对称二羟基化得到的手性二醇通过环硫酸盐以对映特异性的方式重排到旋光性环丁酮上。基于1994年的这些发现，我们已经参与了trichothecane型倍半萜烯的全合成，因为这类成员具有显著的生物活性，如抗真菌、抗菌、抗病毒和杀虫特性，并且该家族的一些成员还抑制肿瘤细胞的生长。然后,我们成功地开发的高效合成环芳香族trichothecanes,如(2 s, 5 s) - (-) 2-methyl-15-nor-6, 8日,10日12-trichothecatetraene, (-) -debromofiliformin, (-) -filiformin, 15-nor-6 (2 r, 5 s), 8日,10日12-trichothecatetraene, (2 r, 5 r, 12 s) 15-nor-6, 8日10-trichothecatriene-12, 13-diol, 12 (2 r, 5 r, s) -12年,13-epoxy-15-nor-6, 8日10-trichothecatriene,和(2 r, 5 r, 12 s) -12年,13-dimethylmethylenedioxy-15-nor-6, 8 10-trichothecatriene, 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