An exploration of the screening of the Wnt signaling path of the Tigliane-type dyridium.

The Tigliane-type terpenes, which are widely found in Odyssey and Rhysnake plants, are a class of natural medicines with unique 5/7/6/3 four-ring skeletons.
compounds are complex in structure, have multiple continuous hand centers, and are biologically active, especially as regulators of protein kinase C (PKC).
typical representative of these compounds, Phorbol-12-myristate-13-acetate (PMA), is now in Phase II clinical studies and has the hope of developing a leukemia treatment drug.
based on its good biological activity, in recent years, these compounds have become a new research hot spot in the field of natural product chemistry and related fields, attracting many chemists at home and abroad to study their organic synthesis and biosynthesis.
In collaboration with The Huang Shengxiong Research Group of the National Key Laboratory for the Sustainable Use of Plant Resources in Kunming Plant Research Institute of the Chinese Academy of Sciences, and Zhao Yong Research Group of Yunnan Normal University, a new Tigliane-type trichomon (1, Figure 1), it has a 6/6/3-three-ring combined 2-methyl-2-cyclic ketone endester structure.
study determined its precise composition through extensive NMR data analysis and ECD computational experiments, and found that it is related to a major Tigliane component 3 (Tetrahedron, 2015, 71 (34), 5484-5493) has a high structural similarity, according to which Huang Shengxiong's research team proposed the possible source synthesis mechanism of the compound, mainly through the three steps of retro-aldol open ring, oxidation and esterification under alkali catalysis (Figure 2 dotted line).
Based on the possible synthesis mechanism of the source, the research team carried out a bionic transformation study of compound 1, and after a series of failed attempts, the research team unexpectedly obtained another one-down terpenes with a novel 5/5/6/3 four-ring skeleton (2, Figure 1).
also confirmed its exact structure through NMR data analysis, ECD calculation and X-ray diffraction experiments.
Next, the research team explored the synthetic conversion mechanism of compound 2 and found that it may have been formed by pulling hydrogen from preform 3 under the action of the strong alkali NaH to form a aldehyde intermediate, and then forming a 5/5/6/3 four-ring bus nucleus through a series of Michael additions, and finally forming an oleol intermediate and a single-line oxygen 1,2-ring plus, losing a carbon atom in the form of methylene acid (Figure 2 solid line).
, the key steps with the oxygen molecule's 1,2-ring addition were validated by a pattern aldehyde compound and 18O2 marker experiment, filling the gap that such reactions have been presented for decades without direct proof.
In addition, Huang Shengxiong Research Group, in collaboration with Li Yan Research Group of the National Key Laboratory of Plant Chemistry and Western Plant Resources in Kunming Plant Institute, screened the Wnt signal path inhibition activity of these new Tigliane dyrones and found significant activity in compound 2 with a 5/5/6/3 four-ring skeleton (Figure 3).
This is the first exploration of the screening of the Wnt signal pathway for Tigliane-type triamcinolone, which also validates the view of the natural product community that natural products of new skeletons with specific activity are likely to be effective against a new type of target."
the above findings were published by Natural and Semisynthetic Tigliane Diterpenoids with New Carbon Skeletons from Euphorbia Dracunculoides as a Wnt Signaling Pathway Interestor (2017, 19, 3911).
research has been funded by the National Natural Science Foundation of China (81522044), yunnan Province High-end Science and Technology Talent Program and the Chinese Academy of Sciences Frontier Key Research Program.
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