Scalable synthesis enabling multilevel bio-evaluations of natural products for discovery of lead compounds

Lizhi Zhu, Wenjing Ma, Mengxun Zhang, Magnolia Muk-Lan Lee, Wing-Yan Wong, Brandon Dow Chan, Qianqian Yang, Wing-Tak Wong (), William Chi-Shing Tai () and Chi-Sing Lee ()
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Lizhi Zhu: Peking University Shenzhen Graduate School
Wenjing Ma: Peking University Shenzhen Graduate School
Mengxun Zhang: Peking University Shenzhen Graduate School
Magnolia Muk-Lan Lee: Hong Kong Polytechnic University
Wing-Yan Wong: Hong Kong Polytechnic University
Brandon Dow Chan: Hong Kong Polytechnic University
Qianqian Yang: Peking University Shenzhen Graduate School
Wing-Tak Wong: Hong Kong Polytechnic University
William Chi-Shing Tai: Hong Kong Polytechnic University
Chi-Sing Lee: Peking University Shenzhen Graduate School

Nature Communications, 2018, vol. 9, issue 1, 1-10

Abstract: 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.

Date: 2018
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DOI: 10.1038/s41467-018-03546-9

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