Total Synthesis of Marine Cyclic Enol-Phosphotriester Salinipostin Compounds

• Published in: Journal of Ocean University of China Vol. 17; no. 3; pp. 683 - 689
• Main Authors: Zhao, Mingliang, Wei, Xianfeng, Liu, Xuemeng, Dong, Xueyang, Yu, Rilei, Wan, Shengbiao, Jiang, Tao
• Format: Journal Article
• Language: English
• Published: Heidelberg Science Press 01.06.2018; Springer Nature B.V; Key Laboratory of Marine Drugs, The Ministry of Education of China, School of Medicine and Pharmacy,Ocean University of China, Qingdao 266003, China%Key Laboratory of Marine Drugs, The Ministry of Education of China, School of Medicine and Pharmacy,Ocean University of China, Qingdao 266003, China; Laboratory for Marine Drugs and Bioproducts, Qingdao National Laboratory for Marine Science and Technology,Qingdao 266003, China
• Subjects: Antiinfectives and antibacterials; Aromatic compounds; Aromatic hydrocarbons; Biodiversity; Biological activity; Carbon 13; Central nervous system; Chemical compounds; Chemical synthesis; Combinatorial analysis; Combinatorial libraries; Deoxyribonucleic acid; Dihydroxyacetone; DNA; Drug discovery; Drugs; Earth and Environmental Science; Earth Sciences; Embedded systems; Fermentation; Frameworks; Lead; Marine biology; Mass spectrometry; Mass spectroscopy; Meteorology; Natural products; Neoplasms; NMR; Nuclear magnetic resonance; Oceanography; Parasites; Pharmacology; Phospholipids; Polycyclic aromatic hydrocarbons; Viruses; enolphosphate trimester; total synthesis; Salinipostin
• DOI: 10.1007/s11802-018-3540-8
• ISSN: 1672-5182

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 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 ( 1 H-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.