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Collective Syntheses and Biological Evaluation of Akuammiline Indole Alkaloids


Natural product chemistry plays a pivotal role in drug discovery. A recent authoritative survey indicated that 61% of marketed drugs in the period of 1981-2002 could be traced to or were inspired by natural products. Since the composition and content of natural products vary from multi-factors, total synthesis has been considered as one of the most important components in the exploration of natural products. The proposal aims at addressing the collective syntheses of a series of bioactive indole alkaloids (strictamine, aspidophylline A and alsmaphorazine C) from a common intermediate. Moreover, bioactivities of these natural products as well as advanced intermediates and analogues will be evaluated by both high throughput screening and focused bioassays to explore their full potential. The target molecules have been reported to possess potent bioactivities, but their very low natural abundance hampered their detailed biological studies. Although considerable synthetic efforts have been made, no total synthesis of strictamine and alsmaphorazine C has been achieved due to their complex molecular architectures. The proposal presents novel and concise synthetic strategies featuring an earlier-stage quaternary carbon formation and a late-stage indole synthesis blueprint. Furthermore, the synthesis could be performed in both protective group-free and asymmetric versions, which perfectly matches the growing demand for economy of synthesis and drug discovery. Since the project is multidisciplinary merging organic chemistry, medicinal chemistry and biology, it will certainly represent a high-quality contribution to the research fields in Europe and may constitute the basis for the discovery of a new generation of potent lead compounds for drug discovery. At the same time, it offers a fantastic opportunity for the candidate to transfer her knowledge and skill to the host lab and Europe, which is beneficial to the European citizens as well as the pharmaceutical industry.

Call for proposal

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Batiment Ce 3316 Station 1
1015 Lausanne

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Activity type
Higher or Secondary Education Establishments
Administrative Contact
Jieping Zhu (Prof.)
EU contribution
€ 207 928,80