Biomedical subjects
Publications and source records attributed to Sandrine Piguel.
A new series of 2-aryl-substituted purine derivatives has been synthesized by Suzuki Pd(0) coupling reactions. Moderate in vitro inhibitory activity against Cdk1 and Cdk5 was observed. These compounds are inactive against GSK3.
The synthesis of three constrained macrocyclic peptide analogues 1 of TMC-95A as potential proteasome inhibitors is described. The key step involves a Ni(0)-mediated macrocyclization of tripeptides 2 bearing halogenated aromatic side chains for the formation of the biaryl junction. In addition, an enantioselective preparation of l-7-bromotryptophan methyl ester 3 using a Corey-O'Donnell alkylation of the glycine benzophenone imine was achieved in good overall yield with very high ee (>85%) on a multigram scale.
The synthesis of 2-substituted-4-benzoxepines and 2,5-disubstituted-4-benzoxepines from aryl iodides and bromoenoates is described. This methodology is based on a palladium-catalyzed aromatic substitution followed by an intramolecular Heck sequence. Under the reaction conditions (Pd(OAc)(2) (10 mol %), tri-2-furylphosphine (20 mol %), norbornene (2 equiv), Cs(2)CO(3) (2 equiv), CH(3)CN, 85 degrees C), moderate to excellent yields of benzoxepines bearing numerous substituents (Me, F, Cl, etc.) are obtained.
[reaction: see text] Iodocyclizations are important transformations and among stereocontrolled iodocyclizations mostly substrate-controlled versions using a chiral auxiliary have been successfully investigated. This work reports on stereoselective reagent-controlled iodolactonizations applying a new method using a combination of ICl and a primary amine leading to the highest selectivities known so far.