Host : Dr William Farnaby

Venue: CeTPD Seminar Room

This seminar is fully funded by external sources

All Welcome 

This seminar explores recent advances in the Foley research group for synthesis and application of natural product-inspired compound libraries. This spans the development of new synthetic methodologies through to the rational design of lead compounds.

The first part of the seminar details the development of synthetic strategies to prepare and modify bridged bicyclic compound libraries. A directed palladation approach for the heteroarylation of an oxabicyclic fragment will be described, [1] adding to the growing reaction toolkit for three-dimensional fragment functionalisation. [2] Our ongoing work investigating the generation and synthetic applications of underexplored bridged bicyclic alkynes to create unusual, fused pharmacophores will then be discussed.[3]

The second half of the talk focuses on the rational design of a selective chemical probe for the splicing-associated kinase CLK4 by systematic modification of quinine-derived inhibitors (quindoles). A newly obtained crystal structure of a lead compound bound to CLK4 will be revealed, providing new opportunities to further refine our inhibitor development. [4] The seminar concludes with discussion of a recent method to completely iterate the aromatic ring in quinine, leading to the generation novel antimalarial compounds.[5,6]

[1] Directed Arylation of 7-Oxabicyclo[2.2.1]heptane to Prepare 3D Fragments. Max J. Caplin, Imogen M. Alderson, and Daniel J. Foley,* Eur. J. Org. Chem. 2024, 27, e202400295.

[2] Emergent synthetic methods for the modular advancement of sp3 -rich fragments. Max J. Caplin and Daniel J. Foley,* Chem. Sci. 2021, 12, 4646.

3] Indirect generation of bridged bicyclic alkynes for the synthesis of novel pharmacophores. Toby G. McDonald and Daniel J. Foley, Unpublished work, 2025.

[4] Rational development of a natural product-derived chemical probe for splicing-associated kinase CLK4. Alexis C. Blackie, Rene Gimpl, Timothy M. Allison, Jodie M. Johnston, Daniel J. Foley, Unpublished work, 2025.

[5] Synthesis of Quinine-Inspired Antimalarials by Ni-Catalysed Cross Electrophile Coupling. Aggie Lawer, Finlay P. Player, Vicky M. Avery,* and Daniel J. Foley,* Adv. Synth. Catal. 2024, 366, 2090.

[6] Site‐Selective Synthetic Modifications of the Cinchona Alkaloids. Finlay P. Player and Daniel J. Foley,* Asian J. Org. Chem. 2024, 13, e202400397.

________________________________________________________________________________

Microsoft Teams Need help?

Join the meeting now

Meeting ID: 381 628 521 495 98

Passcode: 2Ss2EE6s