The 2-arylethylamine motif is very well-known in medicinal chemistry because of its interesting properties when it comes to interacting with the Central Neural System thanks to its ability to pass the blood–brain barrier. This nitrogen-containing family of compounds is of great interest in synthetic organic chemistry and, when it comes to its asymmetric synthesis, great challenges can be faced in order to obtain the chiral purity required in the drug industry. Thus, we provide a concise transition metal review presenting the recent advances in the synthesis of chiral 2-arylethylamines using transition metals as the main catalysts in the introduction of chirality. Both conventional and photocatalysis methods will be covered, considering the main transition metal used in the studies.

Aberrant glycosylation is a recognized hallmark of cancer, establishing Golgi α-mannosidase II (GMII) as strategic therapeutic target. While the natural alkaloid swainsonine demonstrated potent anticancer activity, its clinical use is hampered by toxicity from off-target inhibition of the lysosomal α-mannosidase (LMan). This review surveys computational methodologies advancing inhibitor development from empirical observations to precision structural optimization. We examine the evolution from Molecular Docking to advanced Quantum Mechanics (QM) and Molecular Dynamics (MD), highlighting their combined role in modeling metalloenzyme flexibility and energetics. Analysis reveals that selectivity relies on exploiting peripheral structural divergences, organelle-specific pH gradients, and distinct substrate conformational itineraries. In this context, electronic structure calculations and pKa predictions prove critical for designing “electrostatic switches”, inhibitors binding neutrally at Golgi pH while incurring lysosomal repulsion. Structurally, targeting the non-conserved “anchor site”, mimicking specific transition-state ring distortions and utilizing conformationally restricted scaffolds represent the most effective strategies. Integrating dynamic sampling with rigorous energetic profiling is therefore crucial for developing the next generation of safe, selective GMII inhibitors.