Scaffold hopping via ANCHOR.QUERY:beta-lactams as potent p53-MDM2 antagonists

Using the pharmacophore-based virtual screening platform ANCHOR.QUERY, we morphed our recently described Ugi-4CR scaffold towards a beta-lactam scaffold with potent p53-MDM2 antagonizing activities. 2D-HSQC and FP measurements confirm potent MDM2 binding. Molecular modeling studies were used to understand the observed SAR in the beta-lactam series

Versatile multicomponent reaction macrocycle synthesis using α-isocyano-ω-carboxylic acids

The direct macrocycle synthesis of α-isocyano-ω-carboxylic acids via an Ugi multicomponent reaction is introduced. This multicomponent reaction (MCR) protocol differs by being especially short, convergent, and versatile, giving access to 12–22 membered rings

Instant Macrocyclizations via Multicomponent Reactions

Macrocycles fascinate chemists due to both their structure and their applications. However, we still lack efficient and sustainable synthetic methods, giving us straightforward access to them. Herein, a rapid macrocyclization utilizing a two-step, one-pot approach based on orthogonal multicomponent reaction (MCR) tactics is introduced. This synthetic protocol, which is based on Ugi and Groebke–Blackburn–Bienaymé reactions with isocyanides tethered to alkyl tosylates, yields medium sized macrocycles that are otherwise difficult to achieve. Single crystal structures reveal conformational reorganization via intramolecular hydrogen bonding, and modeling studies profile the synthesized libraries

Instant Macrocyclizations via Multicomponent Reactions

Macrocycles fascinate chemists due to both their structure and their applications. However, we still lack efficient and sustainable synthetic methods, giving us straightforward access to them. Herein, a rapid macrocyclization utilizing a two-step, one-pot approach based on orthogonal multicomponent reaction (MCR) tactics is introduced. This synthetic protocol, which is based on Ugi and Groebke–Blackburn–Bienaymé reactions with isocyanides tethered to alkyl tosylates, yields medium sized macrocycles that are otherwise difficult to achieve. Single crystal structures reveal conformational reorganization via intramolecular hydrogen bonding, and modeling studies profile the synthesized libraries

CCDC 1410886: Experimental Crystal Structure Determination

Related Article: George P. Liao, Eman M. M. Abdelraheem, Constantinos G. Neochoritis, Katarzyna Kurpiewska, Justyna Kalinowska-Tłuścik, David C. McGowan, and Alexander Dömling|2015|Org.Lett.|17|4980|doi:10.1021/acs.orglett.5b02419,An entry from the Cambridge Structural Database, the world’s repository for small molecule crystal structures. The entry contains experimental data from a crystal diffraction study. The deposited dataset for this entry is freely available from the CCDC and typically includes 3D coordinates, cell parameters, space group, experimental conditions and quality measures.

CCDC 1410885: Experimental Crystal Structure Determination

Related Article: George P. Liao, Eman M. M. Abdelraheem, Constantinos G. Neochoritis, Katarzyna Kurpiewska, Justyna Kalinowska-Tłuścik, David C. McGowan, and Alexander Dömling|2015|Org.Lett.|17|4980|doi:10.1021/acs.orglett.5b02419,An entry from the Cambridge Structural Database, the world’s repository for small molecule crystal structures. The entry contains experimental data from a crystal diffraction study. The deposited dataset for this entry is freely available from the CCDC and typically includes 3D coordinates, cell parameters, space group, experimental conditions and quality measures.

Instant Macrocyclizations via Multicomponent Reactions

Macrocycles fascinate chemists due to both their structure and their applications. However, we still lack efficient and sustainable synthetic methods, giving us straightforward access to them. Herein, a rapid macrocyclization utilizing a two-step, one-pot approach based on orthogonal multicomponent reaction (MCR) tactics is introduced. This synthetic protocol, which is based on Ugi and Groebke–Blackburn–Bienaymé reactions with isocyanides tethered to alkyl tosylates, yields medium sized macrocycles that are otherwise difficult to achieve. Single crystal structures reveal conformational reorganization via intramolecular hydrogen bonding, and modeling studies profile the synthesized libraries