Enantioselective Total Syntheses of (+)-Kasugamycin and (+)-Kasuganobiosamine Highlighting a Sulfamate-Tethered Aza-Wacker Cyclization Strategy.

Here, we present the first enantioselective total syntheses of the natural products (+)-kasugamycin, a potent antifungal antibiotic, and (+)-kasuganobiosamine, a compound that results from the degradation of kasugamycin. Salient features of these syntheses include a second-generation enantioselective preparation of a kasugamine derivative (efficiency much improved relative to that of our first chiral-pool effort) and our laboratory's sulfamate-tethered aza-Wacker cyclization.

(S)-2-Carb-oxy-ethyl l-cysteinyl sulfone.

The title compound {systematic name: (2S)-2-aza-niumyl-3-[(2-carb-oxy-ethane)-sulfon-yl]propano-ate}, C6H11NO6S, forms enanti-opure crystals in the monoclinic space group P21 and exists as a zwitterion, with a protonated α-amino group and a deprotonated α-carboxyl group. Both the carboxyl groups and the amino group are involved in an extensive multicentered inter-molecular hydrogen-bonding scheme. In the crystal, the diperiodic network of hydrogen bonds propagates parallel to (101) and involves inter-connected heterodromic R 4 3(10) rings. Electrostatic forces are major contributors to the structure energy, which was estimated by DFT calculations as E total = -333.5 kJ mol-1.

The Development of a Sulfamate-Tethered Aza-Michael Cyclization Allows for the Preparation of (-)-Negamycin tert-Butyl Ester.

We present the first examples of intramolecular aza-Michael cyclizations of sulfamates and sulfamides onto pendant α,ß-unsaturated esters, thioesters, amides, and nitriles. Stirring the substrate with catalytic quantities of the appropriate base delivers the product in good yield and excellent diastereoselectivity. The reactions are operationally simple, can be performed open to air, and are tolerant of a variety of important functional groups. We highlight the utility of this technology by using it in the preparation of a (-)-negamycin derivative.

Facile Oxidation of Ce(III) to Ce(IV) Using Cu(I) Salts.

The synthesis, luminescence, and electrochemical properties of the Ce(III) compound, [(C5Me5)2(2,6-iPr2C6H3O)Ce(THF)], 1, were investigated. Based on the electrochemical data, treatment of 1 with CuX (X = Cl, Br, I) results in the formation of the corresponding Ce(IV) complexes, [(C5Me5)2(2,6-iPr2C6H3O)Ce(X)]. Each complex has been characterized using NMR, IR, and UV-vis spectroscopy as well as structurally determined using X-ray crystallography. Additionally, the treatment of [(C5Me5)2(2,6-iPr2C6H3O)Ce(Br)] with AgF results in the formation of the putative [(C5Me5)2(2,6-iPr2C6H3O)Ce(F)]. The electronic structure of these Ce(IV)-X complexes was investigated by bond analyses and the Ce(IV)-F moiety using quantum chemistry NMR calculations.

From a mercury(II) bis(yldiide) complex to actinide yldiides.

The bis(yldiide) mercury complex, (L-Hg-L) [L = C(PPh3)P(S)Ph2], is prepared from the corresponding potassium yldiide and used to access the first substituted yldiide actinide complexes [(C5Me5)2An(L)(Cl)] (An = U, Th) via salt metathesis. Compared to previously reported phosphinocarbene complexes, the complexes exhibit long actinide-carbon distances, which can be explained by the strong polarization of the π-electron density toward carbon.

Cooperative dihydrogen activation with unsupported uranium-metal bonds and characterization of a terminal U(iv) hydride.

Cooperative chemistry between two or more metal centres can show enhanced reactivity compared to the monometallic fragments. Given the paucity of actinide-metal bonds, especially those with group 13, we targeted uranium(iii)-aluminum(i) and -gallium(i) complexes as we envisioned the low-valent oxidation state of both metals would lead to novel, cooperative reactivity. Herein, we report the molecular structure of [(C5Me5)2(MesO)U-E(C5Me5)], E = Al, Ga, Mes = 2,4,6-Me3C6H2, and their reactivity with dihydrogen. The reaction of H2 with the U(iii)-Al(i) complex affords a trihydroaluminate complex, [(C5Me5)2(MesO)U(µ2-(H)3)-Al(C5Me5)] through a formal three-electron metal-based reduction, with concomitant formation of a terminal U(iv) hydride, [(C5Me5)2(MesO)U(H)]. Noteworthy is that neither U(iii) complexes nor [(C5Me5)Al]4 are capable of reducing dihydrogen on their own. To make the terminal hydride in higher yields, the reaction of [(C5Me5)2(MesO)U(THF)] with half an equivalent of diethylzinc generates [(C5Me5)2(MesO)U(CH2CH3)] or treatment of [(C5Me5)2U(i)(Me)] with KOMes forms [(C5Me5)2(MesO)U(CH3)], which followed by hydrogenation with either complex cleanly affords [(C5Me5)2(MesO)U(H)]. All complexes have been characterized by spectroscopic and structural methods and are rare examples of cooperative chemistry in f element chemistry, dihydrogen activation, and stable, terminal ethyl and hydride compounds with an f element.

Hierarchical 2D honeycomb-like network from barium-seamed nanocapsules.

We report on a two-dimensional hexagonal "honeycomb" network comprising barium-seamed metal-organic nanocapsules involving a hexameric assembly of pyrogallol[4]arene ligands. The incorporated barium ions act as spacers to generate a solvent-accessible void, hierarchical self-assembly having an individual void volume near 13 000 Å3. This work illustrates the surprising chemistry that remains to be discovered by integrating large or classically non-reactive metal ions within supramolecular assemblies, networks, and organic nanocapsules.

Nanocapsules of unprecedented internal volume seamed by calcium ions.

The inception of an unprecedented class of voluminous Platonic solids displaying hierarchical geometry based on pyrogallol[4]arene moieties seamed by divalent calcium ion is described. Single-crystal X-ray structural determination has established the highly conserved geometry of two original Ca2+-seamed nanocapsules to be essentially cubic in shape with C-ethylpyrogallol[4]arene units located along the twelve edges of the cube which are then bridged by metallic polyatomic cations ([Ca4Cl]7+ or [Ca(HCO2)Na4]5+) at the six cube faces. The accessible volume of the nanocapsules is ca. 3500 Å3 and 2500 Å3 and is completely isolated from the exterior of the capsules. These remarkable nanocapsule discoveries cast a spotlight on a marginalized area of synthetic materials chemistry and encourage future exploration of diversiform supramolecular assemblies, networks, and capsules built on calcium, with clear benefits deriving from the intrinsic biocompatibility of calcium. Finally, a proof-of-concept is demonstrated for fluorescent reporter encapsulation and sustained release from the calcium-seamed nanocapsules, suggesting their potential as delivery vehicles for drugs, nutrients, preservatives, or antioxidants.

Redox-Controlled Self-Assembly of Vanadium-Seamed Hexameric Pyrogallol[4]Arene Nanocapsules.

Here we report the controlled self-assembly of vanadium-seamed metal-organic nanocapsules with specific metal oxidation state distributions. Three supramolecular assemblies composed of the same numbers of components including 24 metal centers and six pyrogallol[4]arene ligands were constructed: a VIII24L6 capsule, a mixed-valence VIII18VIV6L6 capsule, and a VIV24L6 capsule. Crystallographic studies of the new capsules reveal their remarkable structural complexity and geometries, while marked differences in metal oxidation state distribution greatly affect the photoelectric conversion properties of these assemblies. This work therefore represents a significant step forward in the construction of intricate metal-organic architectures with tailored structure and functionality.

A copper-seamed coordination nanocapsule as a semiconductor photocatalyst for molecular oxygen activation.

Here we report that a Cu2+-seamed coordination nanocapsule can serve as an efficient semiconductor photocatalyst for molecular oxygen activation. This capsule was constructed through a redox reaction facilitated self-assembly of cuprous bromide and C-pentyl-pyrogallol[4]arene. Photophysical and electrochemical studies revealed its strong visible-light absorption and photocurrent polarity switching effect. This novel molecular solid material is capable of activating molecular oxygen into reactive oxygen species under simulated sunlight irradiation. The oxygen activation process has been exploited for catalyzing aerobic oxidation reactions. The present work provides new insights into designing nonporous discrete metal-organic supramolecular assemblies for solar-driven molecular oxygen activation.

2-Bromo-6-hydrazinyl-pyridine.

The title compound, C5H6BrN3, crystallizes in the ortho-rhom-bic space group P212121 with two mol-ecules with different conformations in the asymmetric unit. In the crystal, N-H⋯N and bifurcated N-H⋯(N,N) hydrogen bonds link the mol-ecules into [100] chains; a short Br⋯Br halogen bond and π-π stacking inter-actions are also observed.

Correction: Isolation of C1 through C4 derivatives from CO using heteroleptic uranium(iii) metallocene aryloxide complexes.

[This corrects the article DOI: 10.1039/D2SC06375A.].

Isolation of C1 through C4 derivatives from CO using heteroleptic uranium(iii) metallocene aryloxide complexes.

The conversion of C1 feedstock molecules such as CO into commodity chemicals is a desirable, but challenging, endeavour. When the U(iii) complex, [(C5Me5)2U(O-2,6- t Bu2-4-MeC6H2)], is exposed to 1 atm of CO, only coordination is observed by IR spectroscopy as well as X-ray crystallography, unveiling a rare structurally characterized f element carbonyl. However, using [(C5Me5)2(MesO)U (THF)], Mes = 2,4,6-Me3C6H2, reaction with CO forms the bridging ethynediolate species, [{(C5Me5)2(MesO)U}2(µ2-OCCO)]. While ethynediolate complexes are known, their reactivity has not been reported in much detail to afford further functionalization. For example, addition of more CO to the ethynediolate complex with heating forms a ketene carboxylate, [{(C5Me5)2(MesO)U}2(µ 2:κ 2:η 1-C3O3)], which can be further reacted with CO2 to yield a ketene dicarboxylate complex, [{(C5Me5)2(MesO)U}2(µ 2:κ 2:κ 2-C4O5)]. Since the ethynediolate showed reactivity with more CO, we explored its reactivity further. A [2 + 2] cycloaddition is observed with diphenylketene to yield [{(C5Me5)2U}2(OC(CPh2)C([double bond, length as m-dash]O)CO)] with concomitant formation of [(C5Me5)2U(OMes)2]. Surprisingly, reaction with SO2 shows rare S-O bond cleavage to yield the unusual [(O2CC(O)(SO)]2- bridging ligand between two U(iv) centres. All complexes have been characterized using spectroscopic and structural methods, and the reaction of the ethynediolate with CO to form the ketene carboxylate has been investigated computationally as well as the reaction with SO2.

ß-d-Galacto-pyranosyl-(1→4)-2-amino-2-de-oxy-α-d-gluco-pyran-ose hydro-chloride monohydrate (lactosamine).

The title compound, C12H24NO10 +·Cl-·H2O, (I), crystallizes in the monoclinic space group P21 and exists as a monohydrate of a monosubstituted ammonium chloride salt, with the reducing carbohydrate portion existing exclusively as the α-pyran-ose tautomer. The glycosidic bond geometry in (I) is stabilized by an intra-molecular hydrogen bond and is close to that found in crystalline α-lactose. All heteroatoms except gluco-pyran-ose ring O4 participate in an extensive hydrogen-bonding network, which propagates in all directions in the crystal structure of (I).

Perfect Polar Alignment of Parallel Beloamphiphile Monolayers: Synthesis, Characterization, and Crystal Architectures of Unsymmetrical Phenoxy-Substituted Acetophenone Azines.

It remains a great challenge to achieve polar order in organic molecular crystals because anti-parallel alignment of side-by-side molecules is intrinsically preferred. We have addressed this problem with a rational design that focuses on the polar stacking of parallel beloamphiphile monolayers (PBAMs) with strong lateral quadrupole-quadrupole attractions. We employ arene-arene interactions as lateral synthons. The first successes were achieved with unsymmetrical donor (X), acceptor (Y) substituted acetophenone azines which form polar PBAMs with double T-contacts between the azines. Near-perfect alignment was achieved with the methoxy series of (MeO, Y)-azines with Y=Cl, Br, I. Here, we report on the synthesis, the characterization (GC/MS, 1 H NMR, 13 C NMR, FTIR), the crystallization, and the single-crystal X-ray analyses of the phenoxy series of (PhO, Y)-acetophenone azines with Y=F, Cl, Br, I. Properties of (RO, Y) azines were computed at the APFD/6-311G* level and are discussed with reference to p-nitroaniline (PNA). This (PhO, Y) series embodies an improved PBAM design based on triple T-contacts which is shown to facilitate faster crystallization and to produce larger crystals. Perfect polar-alignment has been achieved for the phenoxy series of (PhO, Y)-azines with Y=Cl, Br, I and the (PhO, F)-azine also features near-perfect dipole alignment.

Structural and Functional Studies of S-(2-Carboxyethyl)-L-Cysteine and S-(2-Carboxyethyl)-l-Cysteine Sulfoxide.

Insecticidal non-proteinogenic amino acid S-(2-carboxyethyl)-L-cysteine (ß-CEC) and its assumed metabolite, S-(2-carboxyethyl)-l-cysteine sulfoxide (ß-CECO), are present abundantly in a number of plants of the legume family. In humans, these amino acids may occur as a result of exposure to environmental acrylonitrile or acrylamide, and due to consumption of the legumes. The ß-CEC molecule is a homolog of S-carboxymethyl-l-cysteine (carbocisteine, CMC), a clinically employed antioxidant and mucolytic drug. We report here detailed structural data for ß-CEC and ß-CECO, as well as results of in vitro studies evaluating cytotoxicity and the protective potential of the amino acids in renal tubular epithelial cells (RTECs) equipped with reporters for activity of seven stress-responsive transcription factors. In RTECs, ß-CEC and the sulfoxide were not acutely cytotoxic, but activated the antioxidant Nrf2 pathway. ß-CEC, but not the sulfoxide, induced the amino acid stress signaling, which could be moderated by cysteine, methionine, histidine, and tryptophan. ß-CEC enhanced the cytotoxic effects of arsenic, cadmium, lead, and mercury, but inhibited the cytotoxic stress induced by cisplatin, oxaliplatin, and CuO nanoparticles and acted as an antioxidant in a copper-dependent oxidative DNA degradation assay. In these experiments, the structure and activities of ß-CEC closely resembled those of CMC. Our data suggest that ß-CEC may act as a mild activator of the cytoprotective pathways and as a protector from platinum drugs and environmental copper cytotoxicity.

Intramolecular (4+3) Cycloadditions of Oxidopyridinium Ions: Towards Daphnicyclidin A.

N-alkylation of 5-hydroxynicotinic acid esters with electrophiles containing diene functionality produces salts that undergo intramolecular (4+3) cycloaddition reactions upon heating in the presence of base. Initial studies used a three-carbon tether to join the pyridinium ion and diene, revealing some aspects of the inherent selectivity of the reaction with such substrates. Much more challenging was the synthesis of related species possessing only a two-carbon tether. Nevertheless, the cycloaddition of such compounds was successful, leading directly to the ABC ring system of the alkaloid daphnicyclidin A.

Tropane Skeleta from the Intramolecular Photocycloaddition of (4+3) Cycloadducts of Oxidopyridinium Ions and Dienes.

Easily prepared cycloadducts derived from the (4+3) cycloaddition of oxidopyridinium ions with dienes reacted intramolecularly in a [2+2] cycloaddition process to afford complex polycyclic species in which the tropane skeleton was embedded.

Crystal structures of metallocene complexes with uranium-germanium bonds.

The first structural examples of complexes with uranium-germanium bonds are presented, namely, bis-[3,5-bis-(tri-fluoro-meth-yl)phenyl-2κC 1](hydrido-2κH)(iodido-1κI)bis-[1,1(η5)-penta-methyl-cyclo-penta-dien-yl]germaniumuranium(Ge-U), [GeU(C10H15)2(C8H3F6)2HI], and bis-[3,5-bis-(tri-fluoro-meth-yl)phenyl-2κC 1](fluorido-1κI)(hydrido-2κH)bis-[1,1(η5)-penta-methyl-cyclo-penta-dien-yl]germaniumuranium(Ge-U), [GeU(C10H15)2(C8H3F6)2FH]. The two complexes both have a long U-Ge bond [distances of 3.0428 (7) and 3.0524 (7) Å].

Crystal structure of [Th3(Cp*)3(O)(OH)3]2Cl2(N3)6: a discrete mol-ecular capsule built from multinuclear organothorium cluster cations.

An unusually large and structurally complex charge-neutral polynuclear cluster, hexa-µ2-azido-di-µ3-chlorido-hexa-µ2-hydroxido-di-µ3-oxido-hexa-kis-(penta-methyl-cyclo-penta-dien-yl)hexa-thorium-diethyl ether-tetra-hydro-furan (1/0.56/1.44), [Th3(C10H15)6Cl3(N3)6(OH)6O2]·0.56C4H10O·1.44C4H8O or [Th3(Cp*)3(O)(OH)3]2Cl2(N3)6·0.56C4H10O·1.44C4H8O (Cp* = [penta-methyl-cyclo-penta-dien-yl])-, has been crystallized as a mixed tetra-hydro-furan/diethyl ether solvate and structurally characterized. The mol-ecule contains a number of unusual features, the most notable being a finite yet exceptionally long cyclic metal-azido chain. These rare features are the consequence of both sterically protecting Cp* ligands and highly bridging oxide and hydroxide ligands in the same system and illustrate the inter-esting new possibilities that can arise from combining organometallic and solvothermal f-block element chemistry.