Alkyne metathesis: A new tool for the self-assembly of complex molecular architectures

项目目标：开发这一高度收敛的模块化合成策略，通过合成双氮唑的杂芳基类似物，将炔的复分解反应定位为该领域的重要工具(与德国穆尔海姆Max Plank研究所的A.Furstner教授合作优化的催化剂设计)。通过严格的计算机研究启发我们选择杂二唑类化合物，以显示哪些类似物具有最高的预测二聚体/单体和头到尾/头到头的烯烃复分解反应偶联比(与J.Goodman教授合作进行的分子模拟，获得一类新的二唑类化合物，专利文献没有涵盖这些化合物，它们可能更稳定，更容易合成，并具有增强的治疗潜力(表型和RPPA分析与爱丁堡癌症研究中心的N·卡拉格教授合作进行)。这个项目将结合硅胶设计和实验验证，证明钼催化的烷基化合物可以作为一种有效的工具，用于快速自组装具有药用价值的复杂大环结构。

Project Aims:To exploit this highly convergent modular synthetic strategy through the synthesis of heteroaryl analogues ofthe disorazoles, termed "hetero-disorazoles", positioning alkyne metathesis as an important tool in this field(catalyst design optimised in collaboration with Prof. A. Furstner, Max Plank Institute, Mulheim, Germany).Be inspired in our choice of hetero-disorazole targets by rigorous in silico studies to show which analogueshave the highest predicted dimer/monomer and head-to-tail/head-to-head alkyne metathesis coupling ratios(molecular modelling conducted in collaboration with Prof. J. Goodman, University of Cambridge).Access a new class of disorazoles which are not covered by the patent literature and which might be morestable, more synthetically tractable and have enhanced therapeutic potential (phenotypic and RPPA assaysconducted in collaboration with Prof. N. Carragher at the Edinburgh Cancer Research Centre).Combining in silico design with experimental validation, this project will demonstrate that Mo-catalysed alkynemetathesis can be used as an effective tool for the rapid self-assembly of complex macrocyclic architectures ofpharmaceutical interest.