Progress in research on natural products of isopentenyl heteroacyl phloroglucinol (PPAP)

It is an important content and mission of Phytochemistry to explore new compounds with novel structures and significant activities from characteristic natural product groups and important medicinal plant groups The natural products of polycyclic polyisopentenyl substituted acyl phloroglucinol (PPAP) are a kind of special natural products group which are derived from the compound pathway of polyketone and isopentenyl and distributed in the plants of Guttiferae The research began in 1975 Scientists from the former Soviet Union identified the first PPAP compound with the core skeleton of bicyclic [3,3,1] nonane-2,4,9-trione from Hypericum perforatum, a famous Western antidepressant medicinal plant, and aroused the widespread interest of scientists in related fields At present, more than 500 natural ppaps have been reported In addition to the compound pathway characterized by its biogenesis, its core skeleton is more than other three-dimensional and rigid structures rarely seen in other natural product groups, which are also different from the conventional polyphenols such as flavonoids and coumarins, terpenes and alkaloids In addition, its pharmacological activities in anti depression and anti-tumor deserve further exploration and research Xu Gang research group, an important group of Phytochemistry and function research team of Kunming Institute of Botany, Chinese Academy of Sciences, has been engaged in the research work of natural PPAP for a long time He has carried out in-depth research on PPAP components in nearly 20 species of gambogiaceae, and found a large number of compounds with novel structure and significant activity Relevant achievements are in org Lett., chem Commun., SCI China chem And J NAT Prod and other international magazines published nearly 30 original papers In 2018, he was invited to publish papers on chem Rev., the authoritative journal of Top1 in the field of chemistry He summarized and prospected the research progress and development trend in this field, which greatly promoted the research process of natural PPAP Recently, with the support of the Institute's "interdisciplinary leading project kib2017001" and Yunnan provincial key Fund (2015fa032), the research group selected the representative species of different genus and section of gambogiaceae to carry out PPAP targeted research and achieved a series of results In the study of Garcinia subellitica, a representative species of Garcinia, Wang Yongling, a doctoral student, discovered the existence of MS > 900 molecular ion peak by HPLC-MS, and successfully purified the compound garsubelone a through a series of separation and purification methods However, the overlapping and missing of the spectrum signal of the compound pose a great challenge to the confirmation of its structure Finally, the research group determined that garsubelone A is a PPAP dimer with 6 / 6 / 6 / 6 / 6 / 6 / 6 seven ring complex skeleton based on the accumulated experience for many years, and its absolute configuration was determined by X-ray single crystal diffraction The compound should be formed by dehydrogenation of isopentenyl terminal at C-3 position of garsubelone B to form conjugated diene, then by Diels alder cycloaddition reaction and further cyclization with secohyperforin The above research results were published in organic letters (DOI: 10.1021 / ACS Org lett 9b00388) under the title of garsubelone a, the first digital polycyclic polycrystallinols with integrated heptacyclic architecture from Garcinia subelliptica It is the first natural PPAP dimer In the study of Hypericum ascyron, a series of PPAP compounds (nor bpap) with simple cyclohexane as the core structure were found by Hu Yali, a postgraduate student There are 18 such compounds reported in the previous literature, but they have not been paid enough attention because of their simple structure; in 2014, the literature proposed that such compounds may come from bridged PPAP through retro Claisen and decarboxylation reaction (org Lett 2014, 163448 – 3451) In this study, it was found that the side chains of these compounds with simple mother nucleus structure could be further cyclized by [4 + 2] radicals to form PPAP derivatives norascyrones A and B with 6 / 6 / 5 / 6 complex ring system At the same time, it was found that some of the compounds had good cytotoxic activity in vitro At present, the above research results are published on organic letters, (2019, 211007 – 1010; doi: 10.1021/acs.org lett 8b04022) under the title of noracyrones A and B, 2, 3, 4-nor-polycyclic polyphenylated acyloglucinols from Hypericum ascyron In addition, Zhang Xinwen, a postgraduate, discovered a series of isopentenyl heterozygous acyl phloroglucinol derivatives (faberiones A-F) in H faberi of Hypericum group, 1-6) compared with other Hypericum plants, the results show that they are all natural products of isopentenyl heteroacyl phloroglucinol, but the specific structural types are quite different, mainly as follows: (1) compared with the conventional PPAP natural products, the benzene ring is different from the aromatization, and the compounds in Forsythia Yangzi retain the phenolic mother nucleus; (2) isopentenyl is not The further cyclization reaction with phloroglucinol (3) its acyl structure is more diverse than that of conventional PPAP, suggesting that its source is more complex and diverse It is worth mentioning that, although the compound fabriones A-D (1-4) has similar structure with stilbene derivatives, the structural analogues obtained in this study, as well as the structural characteristics and biogenesis of phloroglucinol derivatives of other Hypericum plants, are significantly different from those of conventional stilbene derivatives At present, the above research results have been published on Journal of natural products (np-2018-01006t) under the title of prefabricated acylhologicnols from Hypericum faberi The results also provide an important reference for understanding the biogenic pathway and chemical diversity of isopentenyl heteroacyl phloroglucinol derivatives The above research results not only enrich the research contents of isopentenyl heteroacyl phloroglucinol natural products, but also embody the chemical beauty of structural diversity, complexity of natural products and the particularity of biogenic pathway; at the same time, many molecules are found to have significant pharmacological activities, providing candidates for the discovery of new leading molecules; in addition, it is found that different chemical components of different species have There are significant differences, which provide valuable clues for the exploration of student sources and further exploration and utilization.