Development of a concise synthesis of analogs derived from Amaryllidaceae alkaloids family******************

本提案的重点是UQAM和IntelliSyn制药公司之间的密切合作，以评估和生产在一个旨在完全合成高生物活性小天然产品的基础项目期间获得的类似物。本研究的主要目的是开发一种简明高效的合成方法来合成石蒜科生物碱的类似物。这一家族的天然产物，如石蒜碱、纳西拉辛、潘司他丁及其天然衍生物，因其对多种癌症的重要生物活性而闻名。这些化合物的优势是小的生物活性分子，可以通过全合成大规模获得，而紫杉醇或长春花碱等复杂药物则不是这样。已经开发了一种新的方法来处理这些生物碱；这种方法允许在几个步骤中生产包含关键生物活性部分的主核。这种新的合成方法产生了已知合成途径尚未产生的类似物，并可能打开新的机会。与IntelliSyn Pharma等知名公司的合作将帮助我们生产具有所需物理化学性质的有趣支架。**

This present proposal focuses on a close collaboration between UQAM and IntelliSyn pharma to valorize and produce analogs that have been obtained during a fundamental project aiming the total synthesis of highly bioactive small natural products. The main objective is to develop a concise and efficient synthetic pathway to produce analogs derived from Amaryllidaceae family, an important class of bioactive alkaloids. Natural products from this family such as lycoricidine, narciclasine, pancrastistatin and their natural derivatives are known for their important bioactivity against several cancers. These compounds have the advantage to be small bioactive molecules that can be obtained in large scale by total synthesis, which is not the case with complex drugs such as taxol or vinblastine. A new approach of these alkaloids has been developed; this method allows producing in few steps their main cores containing the crucial bioactive moieties. This new synthetic approach generates analogs that were not yet produced by known synthetic pathways and could open-up novel opportunities. Collaboration with a recognized company such as IntelliSyn pharma will help us to produce interesting scaffolds with required physico-chemical properties.**