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Abstract
Challenges in the development of anti-cancer chemotherapeutics continue to exist, particularly with respect to adverse effects and development of resistance, underlining the need for novel drugs with good safety profiles. Natural products have proven to be a fertile ground for exploitation, and development of anti-cancer drugs from structurally complex natural products holds promise. Unfortunately, this approach is often hindered by low isolation yields and limited information from preliminary cell-based assays. Here we report a concise and scalable synthesis of a series of low-abundance Isodon diterpenoids (a large class of natural products with over 1000 members isolated from the herbs of genus Isodon, which are well-known folk medicines for the treatment of inflammation and cancer), including eriocalyxin B, neolaxiflorin L and xerophilusin I. These scalable syntheses enable multilevel bio-evaluation of the natural products, in which we identify neolaxiflorin L as a promising anti-cancer drug candidate.
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1 Laboratory of Chemical Genomics, School of Chemical Biology and Biotechnology, Peking University Shenzhen Graduate School, Shenzhen 518055, China; Department of Applied Biology and Chemical Technology, Hong Kong Polytechnic University, Hung Hom, Hong Kong, China
2 Laboratory of Chemical Genomics, School of Chemical Biology and Biotechnology, Peking University Shenzhen Graduate School, Shenzhen 518055, China
3 Department of Applied Biology and Chemical Technology, Hong Kong Polytechnic University, Hung Hom, Hong Kong, China
4 Department of Applied Biology and Chemical Technology, Hong Kong Polytechnic University, Hung Hom, Hong Kong, China; State Key Laboratory of Chinese Medicine and Molecular Pharmacology (Incubation), Shenzhen Research Institute of The Hong Kong Polytechnic University, Shenzhen 518057, China; State Key Laboratory of Chirosciences, Department of Applied Biology and Chemical Technology, Hong Kong Polytechnic University, Hung Hom, Hong Kong, China
5 Department of Applied Biology and Chemical Technology, Hong Kong Polytechnic University, Hung Hom, Hong Kong, China; State Key Laboratory of Chinese Medicine and Molecular Pharmacology (Incubation), Shenzhen Research Institute of The Hong Kong Polytechnic University, Shenzhen 518057, China