Total Synthesis of Marine Cyclic Enol-Phosphotriester Salinipostin Compounds  

作　　者：ZHAO Mingliang WEI Xianfeng LIU Xuemeng DONG Xueyang YU Rilei WAN Shengbiao JIANG Tao 

机构地区：[1]Key Laboratory of Marine Drugs, The Ministry of Education of China, School of Medicine and Pharmacy, Ocean University of China [2]Laboratory for Marine Drugs and Bioproducts, Qingdao National Laboratory for Marine Science and Technology

出　　处：《Journal of Ocean University of China》2018年第3期683-689,共7页中国海洋大学学报（英文版）

基　　金：supported by the National Natural Science Foundation of China (No. 81373322);the Innovation Project from Qingdao National Laboratory for Marine Science and Technology (No. 2015ASKJ02);the Taishan Scholar Project Fund of Shandong Province

摘　　要：Due to their structural diversity and variety of biological activities, marine natural products have been the subject of extensive study. These compounds, especially phospholipid polycyclic aromatic hydrocarbons, have a wide range of pharmacological applications, including embedded DNA and central nervous system, anti-tumor, anti-virus, anti-parasite, anti-bacterial, and antithrombotic effects. Unfortunately, the insufficient drug sources have limited the development of these compounds. In this study, we isolated salinpostin compounds from a fermentation solution of marine-derived Salinospora sp., which has a common bicyclic enol-phosphotriester core framework, as well as potent and selective antimalarial activities against P. falciparum with EC_(50)=50 nmolL^(-1). The chemical synthesis of these compounds in greater quantities is necessary for their use in bioactivity studies. Thus we explored a short route with high yields and mild reaction conditions, which can generate combinatorial libraries for drug discovery and lead optimization. We developed a new total synthesis method for six cyclic enol-phosphotriester salinipotin compounds and their diastereomers. For the total synthesis of cyclipostin P, we prepared cyclic enol-phosphotriester salinipostin compounds in 10 steps from a readily accessible starting material, 1,3-dihydroxyacetone, and obtained an overall yield of 1.29%. We fully characterized these compounds by proton nuclear magnetic resonance(~1H-NMR), carbon-13 NMR(^(13)C-NMR), and high-resolution mass spectrometry(HRMS) analyses, and found they coincide absolutely with the same compounds reported previously.Due to their structural diversity and variety of biological activities, marine natural products have been the subject of extensive study. These compounds, especially phospholipid polycyclic aromatic hydrocarbons, have a wide range of pharmacological applications, including embedded DNA and central nervous system, anti-tumor, anti-virus, anti-parasite, anti-bacterial, and anti- thrombotic effects. Unfortunately, the insufficient drug sources have limited the development of these compounds. In this study, we isolated salinpostin compounds from a fermentation solution of marine-derived Salinospora sp., which has a common bicyclic enol-phosphotriester core framework, as well as potent and selective antimalarial activities against P. falciparum with EC50 = 50 nmol L？1. The chemical synthesis of these compounds in greater quantities is necessary for their use in bioactivity studies. Thus we explored a short route with high yields and mild reaction conditions, which can generate combinatorial libraries for drug discovery and lead optimization. We developed a new total synthesis method for six cyclic enol-phosphotriester salinipotin compounds and their diastereomers. For the total synthesis of cyclipostin P, we prepared cyclic enol-phosphotriester salinipostin compounds in 10 steps from a readily accessible starting material, 1,3-dihydroxyacetone, and obtained an overall yield of 1.29%. We fully characterized these compounds by proton nuclear magnetic resonance （1H-NMR）, carbon-13 NMR （13C-NMR）, and high-resolution mass spectrometry （HRMS） analyses, and found they coincide absolutely with the same compounds reported previously.

关 键 词：total synthesis Salinipostin enolphosphate trimester 

分 类 号：O629[理学—有机化学] P734[理学—化学]