Development of novel synthetic strategies for the synthesis of bioactive meroterpenoids

Project Information

NEOTERP

Grant agreement ID: 792320

DOI

10.3030/792320

Project closed

EC signature date 22 March 2018

Start date 1 September 2018

End date 31 August 2020

Funded under

• EXCELLENT SCIENCE - Marie Skłodowska-Curie Actions

Total cost

€ 183 454,80

EU contribution

€ 183 454,80

Coordinated by

IMPERIAL COLLEGE OF SCIENCE TECHNOLOGY AND MEDICINE
United Kingdom

Periodic Reporting for period 1 - NEOTERP (Development of novel synthetic strategies for the synthesis of bioactive meroterpenoids)

Reporting period: 2018-09-01 to 2020-08-31

Summary of the context and overall objectives of the project

The project concerns the development of innovative methodologies for the synthesis of novel bioactive natural products analogues. Thus, the aim of this project is to devise concise synthetic routes for the total synthesis of bioactive meroterpenoids natural products and their analogueues in order to fully explore their potential application for the discovery of new medicines to treat resistant cancers and resistant microbial infections. In particular, polyenes cyclisation via radical-cations intermediates initiated by photoredox catalysis or deriving from substrate that can readily form electrondeficient carbon centres is a highly promising way to induce such a kind of reactivity in substrates not containing strained cyclic “electron-sink” groups.

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

Despite the high-impact CoViD19 disruptions, novel open-chain resorcylate-merotepenoids, have been synthesised. They can be screened in HTS campaigns for their biological activity or used as intermediate in library generation and additional synthetic studies. High resolution mass spectrometric and HPLC evidence about the cyclisation of one of the substrates were gathered.

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)

High resolution mass spectrometric and HPLC evidence about the cyclisation of one of the substrates support the starting intuition of using novel “electron sink” moieties to trigger polycyclisation reactions. Further development can arise in the future, isolating products from this same reaction or applying the concept to different electron-deficient structures.
The novel open-chain meroterpenoids are suitable for further derivatisation and library development campaign.

Summary Picture