Organic Letters: Total synthesis of complex phloroglucinol natural products from the Myrtaceae family

Myrtaceae has about 130 genera and 4500-5000 species, which are distributed in Mediterranean, Madagascar, tropical and temperate regions of Asia, Australia, Pacific Islands and tropical regions of South America This family of plants is rich in acyl phloroglucinol natural products with characteristic tetramethylcyclohexene diketone fragments, which is one of the research hotspots in the field of natural pharmaceutical chemistry In addition, this kind of phloroglucinol has attracted great attention because of its novel structure, complex and wide spectrum of physiological activities Myrtucommulone J and myrtucommuacetalone are natural products of phloroglucinol with important physiological activity and novel structure, which were isolated from Myrtus communis In vitro activity evaluation showed that myrtucomulone J had antibacterial activity, and its mic value was as low as 0.38 μ m (0.25 μ g / ml); its activity was 4 times higher than that of vancomycin, the last barrier in clinical practice, and it had more than 35 times of selective factors for human normal cells, so it was considered to be one of the natural plant antibiotics with rich application prospects Myrtucommuacetalone showed antitumor (T cell proliferation) activity, and its IC50 value was 0.5 μ g / ml Because of their outstanding biological activity and novel structural characteristics, they have become the target molecules in the fields of synthetic chemistry, pharmaceutical chemistry and pharmacology The screening of reaction conditions (source: Organic letters) Tan Haibo, an assistant researcher of South China Botanical Garden, Chinese Academy of Sciences, carried out research on the synthesis of phloroglucinol from myrtucomulone J and myrtucomutacetalone, and found that although the structures reported by them were significantly different, their spectra were highly similar Through further spectral analysis and structural analysis, it is found that the structure of myrtucomulone J is wrongly parsed because of its complexity In fact, it should be the regional isomer of myrtucomumacetalone In order to modify the structure of myrtucomulone J and obtain sufficient amount for subsequent drug evaluation and new drug development and research, the research team was inspired by the synthesis of students, and established an efficient bionic synthesis strategy Based on this synthesis strategy, the first bionic synthesis of myrtucomulone J and myrtucomumacetalone was realized, and the structure of myrtucomulone J was confirmed At the same time, the enantiomers EPI myrtucmullone J and EPI myrtucmullone J and a series of structural analogues were synthesized The implementation of the biomimetic total synthesis research provides a clear transformation process for the analysis of the biosynthesis pathway of the natural products of phloroglucinol among the family members, and also establishes a simple, efficient and reliable synthesis pathway for the rapid and large-scale acquisition of the natural products for the follow-up structure-activity relationship research and new drug development Paper link: http://pubs.acs.org/doi/10.1021/acs.orglett.7b02159