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

项目目标：利用这种高度聚合的模块化合成策略，通过合成异芳基类似的二唑类化合物，称为“杂散二唑”，将炔复合法定位为该领域的重要工具（与德国穆尔海姆马克斯普朗克研究所的A. Furstner教授合作优化了催化剂设计）。在我们选择杂二唑目标时，受到严格的硅研究的启发，表明哪种类似物具有最高的预测二聚体/单体和头对尾/头对头炔复合偶联率（与剑桥大学J. Goodman教授合作进行的分子模型）。获得专利文献中未涵盖的一类新的二唑类，它们可能更稳定，更易于合成，并具有增强的治疗潜力（与爱丁堡癌症研究中心的N. Carragher教授合作进行表型和RPPA测定）。结合芯片设计和实验验证，该项目将证明mo催化的炔元分解可以作为一种有效的工具，用于快速自组装具有药物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.