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

开发源自石蒜科生物碱家族的类似物的简明合成********************

• 批准号: 535879-2018
• 负责人: Canesi, Sylvain
• 金额: $ 1.82万
• 依托单位: Université du Québec à Montréal
• 依托单位国家: 加拿大
• 项目类别: Engage Grants Program
• 财政年份: 2018
• 资助国家: 加拿大
• 起止时间: 2018-01-01 至 2019-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=646782
• 关键词: Development; concise; synthesis; analogs; derived

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.**

本提案重点关注 UQAM 和 IntelliSyn pharma 之间的密切合作，以评估和生产在旨在全合成高度生物活性的小型天然产物的基础项目中获得的类似物。主要目标是开发一种简洁有效的合成途径来生产石蒜科（一类重要的生物活性生物碱）衍生的类似物。该家族的天然产物，如石蒜素、水仙环素、pancrastatatin 及其天然衍生物以其对抗多种癌症的重要生物活性而闻名。这些化合物的优点是生物活性分子小，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然。开发了这些生物碱的新方法；这种方法可以通过几个步骤生产出含有关键生物活性部分的主要核心。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，并且可以开辟新的机会。与 IntelliSyn pharma 等知名公司合作将帮助我们生产具有所需物理化学特性的有趣支架。**