Total Synthesis of Conglobatins using Lithiation-Borylation

Lead Research Organisation: University of Bristol
Department Name: Chemistry

Abstract

Conglobatins are a class of macrodiolide, polyketide-derived natural products that have been shown to possess cytotoxic activity towards the NS-1 myeloma cell line. As a result, conglobatins are an attractive target for total synthesis.

Our lithiation-borylation methodology harnesses iterative, stereospecific boronic pinacol ester homologations to install stereogenic centres. We aim to utilize this chemistry to synthesize known members of the conglobatin family, alongside unnatural analogues. In doing so, we hope to gain a deeper understanding of the structure-activity-relationship of these compounds, as well as aid in the potential identification of conglobatins which have not yet been discovered.

Our lithiation-borylation methodology is ideal for making analogues because it utilizes a small set of common building blocks which can be coupled together, without the need for interim purification.

In summary, this project will not only showcase the use of our lithiation-borylation methodology towards the total synthesis of natural products, but it will also demonstrate the ease by which analogues can be synthesized through simple substitution of one building block for another.

Publications

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Studentship Projects

Project Reference Relationship Related To Start End Student Name
EP/S024107/1 30/09/2019 30/03/2028
2645211 Studentship EP/S024107/1 20/09/2020 19/09/2024 Dylan Rigby