Novel Scaffolds by Mild Photochemical Rearrangement of Reactive Enolate and Organolithium Anions

Project Information

PHOTOLITH

Grant agreement ID: 101023251

DOI

10.3030/101023251

Project closed

EC signature date 23 February 2021

Start date 8 June 2021

End date 7 June 2023

Funded under

• EXCELLENT SCIENCE - Marie Skłodowska-Curie Actions

Total cost

€ 212 933,76

EU contribution

€ 212 933,76

Coordinated by

UNIVERSITY OF BRISTOL
United Kingdom

Periodic Reporting for period 1 - PHOTOLITH (Novel Scaffolds by Mild Photochemical Rearrangement of Reactive Enolate and Organolithium Anions)

Reporting period: 2021-06-08 to 2023-06-07

Summary of the context and overall objectives of the project

The synthesis of potential new pharmaceutical targets and ultimately drug molecules used to treat disease is limited by the ability of chemists to make novel molecular structures. In this work we show that a simple transformation allows a new family of cyclic molecules to be formed in an efficient manner, opening up new scaffolds for use in drug discovery. The original objective was to use light to achieve this aim, but in the event we found an alternative method that gave a range of target structures.

Work performed from the beginning of the project to the end of the period covered by the report and main results achieved so far

Early work showed that the original plan to use a photochemical rearrangement to form new molecular scaffolds was insufficiently general for use in this project. We therefore shifted to the use of spiral lithium amides to promote rearrangements. Early work by the fellow led to a publication showing that structures related to new drug targets could readily be formed using this method. The fellow then moved onto the application of the method towards the formation of medium ring amine targets, which were successfully formed. A publication on this work is in preparation.

Progress beyond the state of the art and expected potential impact (including the socio-economic impact and the wider societal implications of the project so far)

Previous related work had only used chiral starting materials, and not enantioselective deprotonation to form compounds related to the target structures. In addition, we discovered a new stereo retentive SN1 reaction, which is undergoing further investigation, and forms an important mechanistic discovery not previously observed.

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