Construction of consecutive stereogenic centers with high diastereo- and enantioselectivities is a challenging task in organic synthesis. Ir-catalyzed asymmetric allylic substitution reactions with prochiral nucleophiles have evolved as an important method toward this goal. Herein, we report a Cu/Ir relay catalysis allowing for the utilization of alkylcopper reagents, in situ generated from Cu-mediated borylative difunctionalization of styrenes with B(2)pin(2), as nucleophiles compatible with pi-allyl-Ir electrophiles derived from linear allyl carbonates. High yields (up to 90%), excellent regio-, diastereo-, and enantioselectivities are achieved (up to >20:1 b/l, > 20:1 dr, and >99% ee) when appropriate chiral bisphosphine and phosphoramidite ligands are employed. Selective access to all four possible stereoisomers of the target molecule is realized by switching the absolute configurations of the ligands for Cu- and Ir-catalysts. DFT calculations shed light on the stereochemical models in this relay catalysis. An array of product transformations demonstrates the synthetic potential of this reaction.

Acetyl-branched sugars, although relatively rare, are found in certain natural products with notable bioactivities. Herein, we biochemically investigated the biosynthetic pathway of this rare sugar in type II polyketides featuring one-pot enzymatic synthesis of the key acetyl-branched TDP-sugar. The evidence shows that TjhB9/B10 were responsible for the attachment of an acetyl unit, a glycosyltransferase TjhB3 guided the uploading of a branched sugar, and a C7 reductase encoded by a gene outside the biosynthetic gene cluster subsequently reduced the TjhB3 product. Collectively, these results elucidated the sugar tailoring pathway of acetyl-branched sugar-modified polyketides.

Noncovalent porous crystals (NPCs) are exceptionally versatile materials, widely used in sectors like gas separation, catalysis, and disease treatment. Triptycene-based NPCs are particularly distinguished by their rigid structures and considerable internal free volumes, rendering them optimal for designing porous frameworks. However, the principles governing the formation of triptycene-based NPCs have been relatively underexplored. In this study, we synthesized a series of triptycene-based molecules, each maintaining a consistent rigid backbone while varying in side substituents. These modifications introduce a range of intermolecular interactions, establishing a comprehensive platform to systematically assess their influences on crystal architecture and stability. Notably, the variant H-NPC-NPC-CHO exemplifies a unique assembly pattern, robust stability, and potential for scalable synthesis. This research enhances our understanding of how variations in functional groups and backbone packing can affect the structural integrity and functionality of NPCs, thereby facilitating the development of custom-designed materials for specific industrial and environmental applications.

Neuronal accumulation and spread of pathological alpha-synuclein (alpha-syn) fibrils are key events in Parkinson's disease (PD) pathophysiology. However, the neuronal mechanisms underlying the uptake of alpha-syn fibrils remain unclear. In this work, we identified FAM171A2 as a PD risk gene that affects alpha-syn aggregation. Overexpressing FAM171A2 promotes alpha-syn fibril endocytosis and exacerbates the spread and neurotoxicity of alpha-syn pathology. Neuronal-specific knockdown of FAM171A2 expression shows protective effects. Mechanistically, the FAM171A2 extracellular domain 1 interacts with the alpha-syn C terminus through electrostatic forces, with >1000 times more selective for fibrils. Furthermore, we identified bemcentinib as an effective blocker of FAM171A2-alpha-syn fibril interaction with an in vitro binding assay, in cellular models, and in mice. Our findings identified FAM171A2 as a potential receptor for the neuronal uptake of alpha-syn fibrils and, thus, as a therapeutic target against PD.