Hong ran group of Shanghai Institute of organic chemistry, Chinese Academy of Sciences has made important progress in the synthesis of natural products of polyketones

Lasonolide family is a kind of natural product of 20 membered macrolide polyketone, which was isolated from the sponge forcepia sp by American scientists from 1994 to 1997 The biological activity test showed that lasonolide a had a strong anti-tumor activity, and had different interference on the G0 phase of Burkitt lymphoma, promyelocytic cancer, breast cancer and colon cancer cells At the same time, lasonolide a also showed a significant targeting effect on histone phosphorylation, deacetylation and DNA replication of topoisomerase II and MPM2 However, due to the fragility of the marine ecosystem, it is very difficult to obtain the natural products from the nature again, so this natural product has become a hot spot in the research of chemical synthesis and biosynthesis Since the determination of the chemical structure, a total of five research groups have completed the chemical synthesis of the molecule, but most of the synthesis routes are inefficient, so it is difficult to provide the samples and their analogues needed for subsequent studies Hongran group, Key Laboratory of natural product organic synthesis college, Shanghai Institute of organic chemistry, Chinese Academy of Sciences, recently completed the enantioselective total synthesis of lasonolidea (angelw.chem Int ed 2018, 57, 16200) In their research, they ingeniously combined borohydride / oxidation with enzymatic kinetic resolution, providing a new synthesis strategy Kinetic resolution is a classical method for the preparation of chiral compounds, which is characterized by that the R and s configuration products can be obtained by resolution at the same time, but only one enantiomer is often used in the synthesis, and the recycling of the other enantiomer can not avoid additional chemical conversion Total synthesis strategy of lasonolide a (source: Shanghai Institute of organic science, Chinese Academy of Sciences) the research group designed a series of stereoselective borohydride / oxidation methods to separate the R and S Different chiral structural segments of the target molecule were synthesized by parallel routes, and then recombined into the target molecule at the later stage of the total synthesis The chiral efficiency of the kinetic resolution can reach 100% The EKR method and the construction of tetrahydropyran ring with multi chirality center are both the previous synthesis methods developed by the team, and the use of alkyl borane as the protection group of alcohol and acid in the research is also a unique and novel design In this work, 35.8 mg lasonolide a was synthesized with a maximum linear reaction of 15 steps and a total yield of 12%, which laid a methodological foundation for the subsequent accumulation of compounds and the synthesis of analogues The above research work is supported by funds from the "major new drug creation" project of the Ministry of science and technology, the National Natural Science Foundation of China, the Shanghai Municipal Science and Technology Commission, the key research projects of Frontier Science of the Chinese Academy of Sciences, and the strategic leading science and technology project of the Chinese Academy of Sciences (category B).