Siloxycarbene intermediates induced via the visible light irradiation of acylsilanes undergo highly efficient benzoin-type click reactions with pyruvate derivatives. This process requires no reagents ...

A library of potent WEE1 kinase inhibitors was synthesized based on the discontinued frontrunner clinical candidate AZD1775 (1), many of which were more selective for WEE1 over an undesirable off-target of 1, the kinase PLK1. When tested against patient-derived organoids (PDOs) grown from TP53-mutated colorectal cancer (CRC) peritoneal metastases, 34 (IC50 value of 62 nM) exhibited stronger efficacy than 1 (IC50 value of 120 nM) and the best-in-class clinical candidate ZN-c3 (IC50 value of 127 nM). Against primary CRC PDOs with TP53-WT, 34 significantly enhanced DNA damage, replication stress and apoptosis compared to 1, as well as demonstrated high selectivity over patient-matched normal healthy colon PDOs, highlighting a potential therapeutic window for cancer treatment. Overall, this investigation provides critical insight into several potent WEE1 inhibitors that exhibited exceptional efficacy against CRC PDOs and is the first to utilize a PDO platform to assess their effect on healthy and malignant cell viability.

The capacity to engage acylsilanes as carbene precursors, electrophiles, and acyl radical precursors offers significant synthetic potential. However, harnessing the versatility of acylsilanes in chemi...

The School of Chemistry invites applications for a Postdoctoral Research Associate position to work under the supervision of Prof. Andrew Lawrence on a project funded by the Leverhulme Trust. The succ...

We present a Diversity Oriented Clicking approach to synthesize a library of novel clickable N-substituted 2-aminothiazoles which serve as versatile hubs for SuFEx click chemistry diversification. Lev...

Building on our discovery that Ind*Rh(III) catalysts accelerated C(sp2)–H amidation, the Ind*Rh(III) catalysed amidation of C(sp3)–H sites was explored harnessing amides as weakly-coordinating directi...

Building on our discovery that Ind*Rh(III) catalysts accelerated C(sp2)–H amidation, the Ind*Rh(III) catalysed amidation of C(sp3)–H sites was explored harnessing amides as weakly-coordinating directi...

Curated daily chemistry problems. Six attempts to solve the questions, on topics from named reactions to total synthesis.

The visible-light irradiation of acylsilane tethered vinyl ketones promotes an intramolecular Stetter-type reaction via siloxycarbene intermediates. To exploit this unique mode of reactivity, we herei...