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

Myrtaceae has about 130 genera and 4500-5000 species, mainly distributed in the Mediterranean, Madagascar, tropical and temperate regions of Asia, Australia, Pacific Islands, and tropical areas of South America This family of plants is rich in acyl phloroglucinol natural products with characteristic tetramethylcyclohexene diketone fragments, which has been one of the research hotspots in the field of natural pharmaceutical chemistry In addition, this kind of phloroglucinol has attracted great attention in recent years due to its novel structure, complex and wide spectrum of physiological activities Myrtucomulone J and myrtucomutalone are natural products of phloroglucinol with important physiological activity and novel structure isolated from Myrtus communis In vitro activity evaluation showed that myrtucomulone J had significant antibacterial activity, 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 great application prospects Myrtucommuacetalone showed very significant 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 Total synthesis of pyrogallol natural products (source: Organic letters) the natural products chemical biology research group of South China botanical garden ecological and Environmental Science Research Center has been committed to the separation, synthesis, structure-activity relationship and pharmacological mechanism research of antibacterial natural products of myrtle Assistant researcher Tan Haibo, Dr Liu Hongxin and undergraduate student Huo luqiong carried out the research together In the recent review of phloroglucinol in myrtle family, they found that although myrtucommulone J and myrtucommucacetalone were reported to have very obvious differences in structure, 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 group successfully established an efficient bionic synthesis strategy inspired by the synthesis of students Based on this synthesis strategy, the first full synthesis of myrtucomulone J and myrtucomumacetalone was successfully realized and the structure of myrtucomulone J was confirmed At the same time, epi-myrtucmullone J, epi-myrtucmullone J and a series of structural analogues of myrtucmullone J and myrtucmullone were synthesized The implementation of the bionic 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 path 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