Cover Picture: Regioselective and Stereospecific β-Arabinofuranosylation by Boron-Mediated Aglycon Delivery (Angew. Chem. Int. Ed. 46/2023)

Regio- and stereoselective formation of the 1,2-cis-furanosidic linkage has been in great demand for efficient synthesis of biologically active natural glycosides. In this study, we developed a regioselective and β-stereospecific d -/l -arabinofuranosylation promoted by a boronic acid catalyst under mild conditions. The glycosylations proceeded smoothly for a variety of diols, triols, and unprotected sugar acceptors to give the corresponding β-arabinofuranosides (β-Arbf) in high yields with complete β-stereoselectivity and high regioselectivity. The regioselectivity was completely reversed depending on the optical isomerism of the donor used and was predictable a priori using predictive models. Mechanistic studies based on DFT calculations revealed that the present glycosylation occurs through a highly dissociative concerted S_Ni mechanism. The usefulness of the glycosylation method was demonstrated by the chemical synthesis of trisaccharide structures of arabinogalactan fragments.     

Inside Back Cover: Effective Activation of Strong C−Cl Bonds for Highly Selective Photosynthesis of Bibenzyl via Homo-Coupling (Angew. Chem. Int. Ed. 43/2023)

Carbon-carbon (C−C) coupling of organic halides has been successfully achieved in homogeneous catalysis, while the limitation, e.g., the dependence on rare noble metals, complexity of the metal-ligand catalylst and the poor catalyst stability and recyclability, needs to be tackled for a green process. The past few years have witnessed heterogeneous photocatalysis as a green and novel method for organic synthesis processes. However, the study on C−C coupling of chloride substrates is rare due to the extremely high bond energy of C−Cl bond (327 kJ mol⁻¹). Here, we report a robust heterogeneous photocatalyst (Cu/ZnO) to drive the homo-coupling of benzyl chloride with high efficiency, which achieves an unprecedented high selectivity of bibenzyl (93 %) and yield rate of 92 % at room temperature. Moreover, this photocatalytic process has been validated for C−C coupling of 10 benzylic chlorides all with high yields. In addition, the excellent stability has been observed for 8 cycles of reactions. With detailed characterization and DFT calculation, the high selectivity is attributed to the enhanced adsorption of reactants, stabilization of intermediates (benzyl radicals) for the selective coupling by the Cu loading and the moderate oxidation ability of the ZnO support, besides the promoted charge separation and transfer by Cu species.     

Cover Picture: Harnessing the Structure and Dynamics of the Squalene-Hopene Cyclase for (−)-Ambroxide Production (Angew. Chem. Int. Ed. 22/2023)

Terpene cyclases offer enormous synthetic potential, given their unique ability to forge complex hydrocarbon scaffolds from achiral precursors within a single cationic rearrangement cascade. Harnessing their synthetic power, however, has proved to be challenging owing to their generally low catalytic performance. In this study, we unveiled the catalytic potential of the squalene-hopene cyclase (SHC) by harnessing its structure and dynamics. First, we synergistically tailored the active site and entrance tunnel of the enzyme to generate a 397-fold improved (−)-ambroxide synthase. Our computational investigations explain how the introduced mutations work in concert to improve substrate acquisition, flow, and chaperoning. Kinetics, however, showed terpene-induced inactivation of the membrane-bound SHC to be the major turnover limitation in vivo. Merging this insight with the improved and stereoselective catalysis of the enzyme, we applied a feeding strategy to exceed 10⁵ total turnovers. We believe that our results may bridge the gap for broader application of SHCs in synthetic chemistry.     

Inside Cover: Uniform Growth of Nanocrystalline ZIF-8 on Cellulose Nanocrystals: Useful Template for Microporous Organic Polymers (Angew. Chem. Int. Ed. 24/2023)

Zeolitic imidazolate framework (ZIF-8) nanocrystals were uniformly grown on the surface of cellulose nanocrystals (CNCs) to give a hybrid material, ZIF@CNCs. By varying the stoichiometry of the components, it was possible to control the size of the ZIF-8 crystals grown on the CNC surface. Optimized ZIF@CNC ( ZIF@CNC-2 ) was used as a template to synthesize a microporous organic polymer (MOP), ZIF@MOP@CNC . After etching the ZIF-8 with 6 M HCl solution, a MOP material with encapsulated CNCs ( MOP@CNC ) was formed. Zinc coordination into the porphyrin unit of the MOP yielded the ship-in-a-bottle structure, Zn MOP@CNC , comprised of CNCs encapsulated within the Zn-MOP. In comparison to ZIF@CNC-2 , Zn MOP@CNC showed better catalytic activity and chemical stability for CO₂ fixation, converting epichlorohydrin to chloroethylene carbonate. This work demonstrates a novel approach to create porous materials through CNC templating.