Research Progress in Area 4 方向 ( 四 ) 課題進展 183 Abstract Natural products have served as a rich source of novel molecular entity and diversity, and are valuable compound leads for discovery and development of effective medicine for treatment and cure of human diseases. This project aims at expanding our current research effort on total synthesis of marine macrolides and moving one step forward to discover anticancer hit compounds among the synthesized intermediates and simplified analogues of marine macrolides. The main activities of this project include completion of total synthesis of selected macrolides and related analogues. A scale-up synthesis is planned to access the bioactive hit compounds for further confirmation of anticancer activity using a panel of selected cell lines. Research Activities and Progress • Accomplished total synthesis of maltepolide E (Fig. 1) and its congeners as well as the C19truncated cores of maltepolides; • Carried out cytotoxicity assay of some synthetic intermediates and natural product analogues using L929 mouse fibroblast cell line (Fig. 2); • Completed the synthesis of the proposed structure of iriomoteolide-13a (Fig. 1). Key Findings • The preliminary cytotoxicity of the synthesized C19-truncated maltepolide cores and analogues reveals the essential structural units for bioactivity of the natural products (Fig. 2; IC50 of maltepolide E = 6.8 µM); • The structures of maltepolides A, B, and E have been confirmed by total synthesis; • The proposed structure of iriomoteolide-13a has been confirmed not correct by chemical synthesis, suggesting further synthetic study for structural revision. Research Output Publication 1 Trained personnel 3 Exploration of Marine Natural Products for Discovery of Anticancer Leads Prof. Wei-Min Dai The Hong Kong University of Science and Technology Fig 1. Structures of maltepolide E and proposed iriomoteolide-13a
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