Highly Enantioselective Synthesis of Pharmaceuticals at Chiral-Encoded Metal Surfaces.

Invited for the cover of this issue are the groups of Chularat Wattanakit and Alexander Kuhn at the Vidyasirimedhi Institute of Science and Technology and the University of Bordeaux. The two tunnels in the image illustrate the entrance into a porous heterogeneous catalyst for the stereoselective transformation of adrenalone into the desired epinephrine stereoisomer. Read the full text of the article at 10.1002/chem.202302054.

Highly Enantioselective Synthesis of Pharmaceuticals at Chiral-Encoded Metal Surfaces.

Enantioselective catalysis is of crucial importance in modern chemistry and pharmaceutical science. Although various concepts have been used for the development of enantioselective catalysts to obtain highly pure chiral compounds, most of them are based on homogeneous catalytic systems. Recently, we successfully developed nanostructured metal layers imprinted with chiral information, which were applied as electrocatalysts for the enantioselective synthesis of chiral model compounds. However, so far such materials have not been employed as heterogeneous catalysts for the enantioselective synthesis of real pharmaceutical products. In this contribution, we report the asymmetric synthesis of chiral pharmaceuticals (CPs) with chiral imprinted Pt-Ir surfaces as a simple hydrogenation catalyst. By fine-tuning the experimental parameters, a very high enantioselectivity (up to 95 % enantiomeric excess) with good catalyst stability can be achieved. The designed materials were also successfully used as catalytically active stationary phases for the continuous asymmetric flow synthesis of pharmaceutical compounds. This illustrates the possibility of producing real chiral pharmaceuticals at such nanostructured metal surfaces for the first time.

Heterochiral-to-Homochiral Structural Transformation in Metallosupramolecular Ionic Crystals.

Here, we report a unique transformation from heterochiral to homochiral structures in ionic crystals composed of complex cations and complex anions. Treatment of an anionic AuI3CoIII2 complex, ΛΛ-[Au3Co2(d-pen)6]3- ([1]3-; H2pen = penicillamine), with M = MnII, CoII, NiII, ZnII in water in the presence of 1,10-phenanthroline (phen) commonly gave ionic crystals formulated as [M(phen)2(H2O)2][Na(H2O)6][{M(phen)2(H2O)}(1)]3 (2M), in which [M(phen)2(H2O)2]2+ and [M(phen)2(H2O)]2+ adopt Δ and Λ configurations, respectively. While 2Co, 2Ni, and 2Zn were all stable in each mother liquor, 2Mn was converted to [Mn(phen)3]3[1]2·phen (3Mn) containing the Λ configurational [Mn(phen)3]3+ under the same conditions. 3Mn showed a water adsorption capacity higher than that of 2Mn, despite its lower porosity of crystal.

Self-assembly of cyclic hexamers of γ-cyclodextrin in a metallosupramolecular framework with d-penicillamine.

Cyclodextrins are widely used cyclic oligosaccharides of d-glucose whose hydrophilic exterior is covered by hydroxyl groups and whose hydrophobic interior is surrounded by lipophilic moieties. Because of this structural feature, cyclodextrin molecules commonly aggregate into dimensional structures via intermolecular hydrogen bonds, and their aggregation into closed oligomeric architectures has been achieved only via the attachment of functional substituent groups to the cyclodextrin rings. Here, we report the first structurally characterized self-assembly of non-substituted γ-cyclodextrin molecules into cyclic hexamers, which was realized in a chiral coordination framework composed of complex-anions with d-penicillamine rather than l- or dl-penicillamine. The self-assembly is accompanied by the 3D-to-2D structural transformation of porous coordination frameworks to form helical hexagonal cavities that accommodate helical γ-cyclodextrin hexamers. This finding provides new insight into the development of cyclodextrin chemistry and host-guest chemistry based on chiral recognition and crystal engineering processes.