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

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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