Research Progress in Area 4 方向 ( 四 ) 課題進展 181 Abstract Themarine environment harbors a large number of microorganisms that are the source of structurally diverse bioactive secondary metabolites. The isolation approach to obtain these bioactive marine compounds is too expensive or unsustainable to the modern drug discovery. Chemical synthesis is used as a powerful tool to address the problems of structural diversity and supply of bioactive marine natural products, which bridges the gap between drugs and marine natural products in the development of new drugs. In this project, we propose to 1) synthesize several marine natural products of important biological activities including anticancer and antibiotics, 2) mimic haloperoxidases of marine microorganisms for halogenation and oxidation reactions, 3) develop new and efficient methodologies for synthesis of medicine-valued heterocyclic molecules. Research Activities and Progress • Collective total synthesis of marine natural products lepadins A-E with anticancer activity; • Collective total synthesis of bioactive indole alkaloids; • Mimicking haloperoxidase for bromide oxidation and application Key Findings • A concise and green strategy was developed for scalable collective total synthesis of lepadins A-E, H and ent-I in 13-18 steps with 3-11% overall yield; • The first catalytic asymmetric alkynylation of 3,4-dihydro-beta-carbolinium ions is developed for synthesis of a library (42 compounds) of bioactive indole alkaloids including seven natural products: harmicine, geissoschizol, geissoschizine, akuammicine, desethyleburnamonine, eburnamonine, and larutenine; • For the first time, haloperoxidase was successfully mimicked under neutral condition to produce reactive brominating species by oxidation of bromide with hydrogen peroxide. Research Output Publication 7 Trained personnel 10 Drugs from the sea: Chemical Synthesis of Bioactive Marine Natural Products Prof. Rongbiao Tong The Hong Kong University of Science and Technology Fig 1. Collective total synthesis of bioactive natural products
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