The latest research of academician Yue Jianmin's team: discovery of new natural diterpenoid vitamin C conjugate and biogenic inspired total synthesis

Author: Dr Zhao Jinxin's natural products are an important source of drug discovery The branches and leaves of Hong Kong mahogany, which belongs to neem family, are often used to treat malaria by local people in Yunnan Province Recently, Dr Zhao Jinxin and others from the team of academician Yue Jianmin of Shanghai Pharmaceutical Research Institute of Chinese Academy of Sciences found a new type of natural diterpenoid vitamin C conjugate, named hongkonoids A-D (1-4), which is the first reported diterpenoid vitamin C conjugate (j.am Chem SOC 2018, 140, 2485 − 2492 Doi: 10.1021/jacs.7b10135) Figure 1 The structure of hongkonoids A-D (1-4) the structure of this kind of natural product is mainly determined by comprehensive analysis of nuclear magnetic data, chemical degradation, X-ray single crystal diffraction, circular dichroism and total synthesis It is suggested that this kind of structural biogenesis may be obtained from a series of key steps such as Claisen rearrangement of vitamin C and GGPP condensate Inspired by this, the author has completed the total synthesis work in 12 to 14 steps with the total yield of 5.4% to 9.6% The key step of this method is a one pot reaction from 12 to 14, including Claisen rearrangement, deprotection and 5-exo-trig cyclization Fig 2 During the synthesis of hongkonoids A-D (1-4), the authors tested the NF - κ B inhibitory activity of diterpenoid vitamin C conjugate 1 − 4, intermediate analogue 12 epi-2, 33 and 34, among which compound 1 and two intermediates 33 and 34 showed some inhibitory activity The most active compound 34 has a significant inhibitory effect on LPS induced inflammation in two macrophages, raw 246.7 and bmdm Fig 3 The result of compound 34 inhibiting LPS induced inflammatory response in macrophages was published in Journal of the American Chemical Society under the title of "structural isolation and bio inspired total syntheses of ascorbic diphenoid hongkonoids a − D" The author of this paper is Jin Xin Zhao, Yan Yan Yu, Sha Sha Wang, Su Ling Huang, Yushen, Xin Hua Gao, Li Sheng, Jing Ya Li, Ying Leng, Jia Li, and Jian Min Yue, academician Yue Jianmin