Intranasal Carrier-Free Nanomodulator Addresses Both Symptomatology and Etiology of Alzheimer's Disease by Restoring Neuron Plasticity and Reprogramming Lesion Microenvironment.

The unsatisfactory treatment outcome of Alzheimer's disease (AD) can be attributed to two primary factors, the intricate pathogenic mechanisms leading to restricted treatment effectiveness against single targets and the hindered drug accumulation in brain due to blood-brain barrier obstruction. Therefore, we developed a carrier-free nanomodulator (NanoDS) through the self-assembly of donepezil and simvastatin for direct nose-to-brain delivery. This approach facilitated a rapid and efficient traversal through the nasal epithelial barrier, enabling subsequent drug release and achieving multiple therapeutic effects.

Cross-Coupling of Cyclobutenone -Tosylhydrazones with Organohalides: Access to Conjugated Enynes and Enallenes via a Strained Allylpalladium Intermediate.

A palladium-catalyzed cross-coupling reaction of cyclobutenone -tosylhadrazones with organohalides is disclosed. The protocol involves the generation of a strained allylpalladium intermediate from readily available starting materials through palladium carbene migratory insertion, which undergoes electrocyclic ring opening and β-hydride elimination for the production of conjugated enynes and enallenes. The broad substrate scope, good to excellent yields, and tunable product diversity make the protocol potentially useful in organic synthesis.

Palladium-Catalyzed Carbene Coupling Reactions of Cyclobutanone -Sulfonylhydrazones.

Described herein are the palladium-catalyzed cross-coupling reactions of cyclobutanone-derived -sulfonylhydrazones with aryl or benzyl halides, suggesting that the metal carbene process and β-hydride elimination can smoothly occur in strained ring systems. Structurally diversified products including cyclobutenes, methylenecyclobutanes, and conjugated dienes are selectively afforded in good to excellent yields. Preliminary success in asymmetric carbene coupling reactions in strained ring systems has been achieved, providing a promising route for the synthesis of enantioenriched four-membered-ring molecules.