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

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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.