Diversity Synthesis Using Glutarimides as Rhodium Carbene Precursors in Enantioselective C–H Functionalization and Cyclopropanation DOI Creative Commons
William F. Tracy,

Jack C. Sharland,

Duc Ly

et al.

Journal of the American Chemical Society, Journal Year: 2025, Volume and Issue: unknown

Published: March 18, 2025

Cereblon E3 ligase modulatory drugs (CELMoDs) can be used to target proteins and mark them for proteasomal degradation by recruiting cereblon (CRBN), the substrate receptor of CRL4CRBN ubiquitin complex. Modifications stereochemistry regiochemistry distal functionality on CELMoDs have been shown large effects activity selectivity; however, methods allowing rapid selective introduction enantioenriched moieties are rare. Herein, we report that classical CRBN-binding glutarimide cores successfully derivatized aryl diazoacetates. These diazo derivatives, when in presence a dirhodium catalyst, undergo high-yielding highly enantioselective C–H functionalization hydrocarbons cyclopropanation styrene. products create not only molecular glue degrader-like compounds but also intermediates elaborated into effective bifunctional ligand-directed degraders. Our findings highlight both effectiveness catalysis drug discovery context new method preparing diverse stereoenriched glutarimide-containing compounds.

Language: Английский

Applications of innovative synthetic strategies in anticancer drug Discovery: The Driving Force of new chemical reactions DOI
Han Wang, Xiaolong Ma, Lingyi Sun

et al.

Bioorganic & Medicinal Chemistry Letters, Journal Year: 2025, Volume and Issue: 119, P. 130096 - 130096

Published: Jan. 9, 2025

Language: Английский

Citations

1
Diversity Synthesis Using Glutarimides as Rhodium Carbene Precursors in Enantioselective C–H Functionalization and Cyclopropanation DOI Creative Commons
William F. Tracy,

Jack C. Sharland,

Duc Ly

et al.

Journal of the American Chemical Society, Journal Year: 2025, Volume and Issue: unknown

Published: March 18, 2025

Cereblon E3 ligase modulatory drugs (CELMoDs) can be used to target proteins and mark them for proteasomal degradation by recruiting cereblon (CRBN), the substrate receptor of CRL4CRBN ubiquitin complex. Modifications stereochemistry regiochemistry distal functionality on CELMoDs have been shown large effects activity selectivity; however, methods allowing rapid selective introduction enantioenriched moieties are rare. Herein, we report that classical CRBN-binding glutarimide cores successfully derivatized aryl diazoacetates. These diazo derivatives, when in presence a dirhodium catalyst, undergo high-yielding highly enantioselective C–H functionalization hydrocarbons cyclopropanation styrene. products create not only molecular glue degrader-like compounds but also intermediates elaborated into effective bifunctional ligand-directed degraders. Our findings highlight both effectiveness catalysis drug discovery context new method preparing diverse stereoenriched glutarimide-containing compounds.

Language: Английский

Citations

0