Angewandte Chemie International Edition

A low-temperature polymorph is found to exist for [D₅]pyridine that does not exist for [H₅]pyridine. In their Communication on page 755 ff., R. Boese, S. Parsons, and co-workers report the unusual complexity of the solid-state structures of one of the simplest heteroaromatic molecules. Pyridine shows the unusual property of isotopic polymorphism, which is rare for organic or molecular compounds as isotopic substitution rarely has an effect on the stabilities of crystal structures.

A D₂-symmetric chiral tetraaminophosphonium salt functions as an effective phase-transfer catalyst to achieve highly stereoselective alkylation of C-terminal azlactones of growing peptides, as described by T. Ooi and co-workers in their Communication on page 733 ff. The judicious combination of this method with a direct ligation process is a practical strategy for incorporating various chiral, non-racemic α,α-dialkyl-α-amino acids into a specific site of the peptide strand.

Keen for a share in the glory: Until recently, the title reaction stood in the shadows, its famous sister, catalytic allylic substitution, in the limelight. Catalytic propargylic substitution has now emerged as an efficient transformation that can be catalyzed by a variety of transition metals (see picture). Among the recent developments are copper-catalyzed asymmetric propargylic amination reactions. Nu = nucleophile

Choosing the right metal for the job: A broad range of asymmetric conjugate addition reactions are catalyzed efficiently by copper complexes, provided the appropriate organometallic reagent is used. With aluminum reagents, for example, quaternary stereogenic centers with functionalized aryl substituents can be generated with high enantioselectivity (see scheme).

Next-generation nanomaterials: The coordination-directed assembly of metal ions and organic bridging ligands has afforded bulk-scale functional hybrid materials. Their scaling-down to the nano-regime has led to nanoscale coordination polymers and metal–organic frameworks which have been used in a broad range of applications including catalysis, spin-crossover, templating, biosensing, biomedical imaging, and anticancer drug delivery.

Exciting developments in the area of antibiotics are discussed in this stimulating review article as the authors present highlights of research carried out since the year 2000, emphasizing the pivotal role that total synthesis plays in moving the field forward and into new possibilities of drug design. The three compounds are shown as an illustration of the structural diversity of antibiotics.

Finding the middle ground: A 1:1 host–guest complex consisting of a hexa-peri-hexabenzocoronene molecule sitting in the middle of the free cavity of a giant π-conjugated carbazole macrocycle has been obtained (see STM image). The complex has been prepared by physisorption of a monolayer of macrocycles followed by gas-phase deposition of graphene molecules by pulsed laser deposition.

From the ocean: Ammosamides A (1) and B (2) were isolated from a marine-derived Streptomyces species collected in the Bahamas. The structures of these chlorinated tricyclic pyrroloquinoline alkaloids were solved using X-ray crystallographic techniques. Ammosamide A (1) was shown to contain an unusual thio-γ-lactam ring. Both metabolites show specific nanomolar cytotoxicity against selected cancer cell lines.

The protein target of the ammosamides, cytotoxic natural products from a marine-derived actinomycete, has been elucidated. An immunoaffinity fluorescent tag was used to construct a fluorescent molecular probe (see structure). First, uptake and localization of the probe in cells was visualized with fluorescence microscopy. The probe was then used to co-immunoprecipitate proteins that bound to the ammosamide core. Myosin was thus identified as a target.

Dual-purpose activation: Peptide C-terminal azlactones I undergo stereoselective alkylation with high efficiency by the use of a newly devised chiral tetraaminophosphonium salt as a phase-transfer catalyst, and the alkylated azlactone products II can be employed directly for peptide ligation (see scheme, LG=leaving group). In this way, a wide range of chiral quaternary α-amino acid residues can be incorporated at specific sites of a peptide strand.

Mixed company: The use of a mixed carbonyl/cyanide ligand set enables stabilization of two new heptacoordinate complexes: [W(CN)₅(CO)₂]³⁻ and [W(CN)₅(CO)₂]²⁻. In the trianionic complex the two carbonyl ligands occupy the axial positions. Remarkably, one-electron oxidation causes loss of this axial symmetry, as shown by X-ray crystallography (see picture, orange W, gray C, blue N, red O), IR, and EPR spectroscopy.

Glowing with pride: An activator-free gallium oxalatophosphite is a new class of color conversion phosphors for NUV and blue light-emitting diodes. It is synthesized by using an organic template and an environmentally friendly eutectic solvent in a reaction that shows efficient atom economy. The resulting material has a tubular structure (see picture) and intriguing luminescence properties.

Devices and desires: The self-assembly of single-molecule-magnet (SMM) carbon-nanotube (CNT) hybrids (see picture) in conditions compatible to the creation of electronic devices is described. The process is controlled at the single-molecule level, and the resulting CNT–field-effect transistors display single-SMM sensitivity at room temperature.

A sheep in wolf's clothes? Mimicking the crucial conformational step in viral fusion promises to be an efficient method to detect potential antagonists of retroviral infection (see scheme). Reconstituted lipopeptides derived from the N peptides of the class I virus fusion protein of SIV serve as receptors for potential inhibitors that function like the C peptides of the virus protein.

Not so simple: It is normally assumed that deuteration has only a minor effect on the stabilities of crystal structures. This assumption is wrong for pyridine. A low-temperature polymorph exists for [D₅]pyridine, but not for [H₅]pyridine, which adds a further twist to the already unusual structural chemistry of one of the simplest and most familiar laboratory chemicals.

A facile synthesis of N-hydroxypyrroles has been developed using readily available α-carbonyl oximes and α,β-unsaturated aldehydes. The domino reaction proceeds through iminium activation of α,β-unsaturated aldehydes, Michael addition using oximes as N-selective nucleophiles, and aldol condensation.

The first catalytic route toward the title compounds by asymmetric ring-closing metathesis is described. A remarkable reversal of enantioselectivity is observed when the achiral imido ligand of the chiral molybdenum-catalyst is changed (see scheme), thus highlighting the importance of the achiral and the chiral ligands in catalyst design.

All in the family: Knowledge of the biosynthesis of NN containing natural products is limited. Feeding experiments with ¹³C and ¹⁵N-labeled molecules establish that the phthalazinone core of azamerone is derived from the diazo chlorinated meroterpenoid SF2415A3. A biosynthetic mechanism involving an oxidative rearrangement of the aryl diazoketone followed by rearomatization with the dinitrogen group is proposed.

Fixed chirality: The treatment of cyclooctapyrroles (see picture) with a metal source with optically active carboxylate or amine ligands leads to enantioselective metalation to give stereochemically stable helical mononuclear and dinuclear complexes without a chiral auxiliary. The helicity of the dicopper complex was determined by the simulation of the CD spectrum on the basis of X-ray crystallographic data.

Hydrogen-bond activation by a diol promotes enantioselective Mukaiyama aldol reactions of acyl phosphonates. This mild and general method gives α-hydroxy phosphonate products having two chiral centers, one tertiary and one quaternary, formed with high diastereo- and enantioselectivity.

Rings around the wire: Novel hierarchical heterostructures, assembled by radial deposition of InAs on GaAs nanowires with nonplanar side walls, result in the formation of InAs nanorings. The mechanism of formation of such structures, determined by transmission electron microscopy, involves the preferential nucleation of InAs at concave regions of the GaAs surface by capillarity effects.

Instant carbenes—that's hot: The thermal 1,2-Brook rearrangement of acylsilanes generates siloxycarbene intermediates that can undergo intramolecular CH bond insertion to provide benzofuran derivatives. This metal-free tandem reaction occurs in less than 10 minutes in the microwave.

One pot+two steps=three stereocenters: A short enantioselective synthesis to access the indolo[2,3a]quinolizidine and the benzo[a]quinolizidine skeleton has been developed (see scheme; TMS=trimethylsilyl, R¹=aromatic, R²=3-indoyl or 3,4-dimethoxyphenyl). The sequence involves an organocatalytic conjugate addition and subsequent acid-catalyzed cyclization of the acyliminium ion.

Joined at the Cs: A novel intermolecular decarboxylative CC, CC, and CC_sp coupling catalyzed by CuBr and using α-amino acids as starting materials has been developed (see scheme). Various functionalized nitrogen-containing compounds were obtained by this method.

An exclusive club: The first member of an unprecedented class of polyunsaturated and polyhydroxylated macrocycle, belizeanolide (see structure), has been isolated from a marine dinoflagellate. The corresponding open form, belizeanolic acid, was also found. Their structures were determined primarily by analysis of NMR spectroscopic data. Both compounds showed significant antiproliferative activities.

Direct condensation of β-arylketones with acetamide afforded both Z and E enamides. The Z-configured substrates underwent hydrogenation with excellent enantioselectivity by using the Rh/tangphos catalytic system (see scheme; tangphos=1,1′-di-tert-butyl-[2,2′]-diphospholanyl). The product β-arylisopropylamines are important precursors to several drugs.

Sly like a “DBFOX”: The chiral α-hydroxy malonate 2 can be prepared in high yield and with up to 98 % ee from racemic malonate 1 through α-hydroxylation using oxaziridine 3 and is catalyzed by the (R,R)-DBFOX-Ph/Ni^II complex (see scheme). Biologically useful molecules have been prepared by using this method and illustrate its efficiency.

Reaction without ZnZn rupture: [Zn₂] reacts with a fourfold excess of the strong Lewis base 4-dimethylaminopyridine (dmap) to unexpectedly form the Lewis acid–base adduct 1, in which both dmap molecules coordinate in a geminal binding mode to only one zinc atom. Cp*=C₅Me₅.

In pocket: A new class of potent inhibitors of factor Xa features a quaternary ammonium ion to fill the aromatic box in the S4 pocket and a 2-chlorothiophenyl group to occupy the S1 pocket (see picture; red O, blue N, yellow S, green Cl). Changing from a primary to a quaternary ammonium ion increases the binding affinity by a factor of 1000. The poor affinity in the former case suggests negligible cation–π interactions between Lys and Trp.

On the ball: Charge transfer occurs readily in tightly interacting complexes formed from π-extended tetrathiafulvalenes, which act as pincerlike receptors, and C₆₀ in a variety of solvents upon photoexcitation (see picture; PET=photoelectron transfer). It should be feasible to construct simple photovoltaic devices from systems based on similar recognition motifs.

The anisotropy of the folding-energy landscape of proteins under force can be tested with cysteine engineering. The shorter the actively contracting polypeptide (see scheme, from blue to green), the higher the force at which the protein folds. The anisotropy of the folding mechanics can be described surprisingly simply with the help of a minimal model, mainly considering the entropic elasticity of the polypeptide.