Angewandte Chemie International Edition

A two-peptide lantibiotic … is active against certain pathogenic bacteria in nanomolar concentrations. In their Communication on page 9472 ff., J. C. Vederas and co-workers describe the first solid-supported synthesis of lacticin 3147, the bis(desmethyl) analogue of lacticin A2. This compound shows potent synergistic antimicrobial activity in the presence of lacticin A1. Other lantibiotics can be prepared for the study of structure–activity relationships by using this strategy. Annie Tykwinski is thanked for the cover graphic design.

Iron–sulfur proteins of the Rieske type contain a redox-active [2Fe-2S] site that can be described as a variant of the related ferredoxins, but with unsymmetrical Cys₂His₂ coordination. This unusual Fe/S cluster could now be emulated in a synthetic model for the first time, using relatively simple ligands. In their Communication on page 9537 ff., F. Meyer and co-workers report the successful synthesis as well as the spectroscopic and structural characterization of the biomimetic analogue, which was also analyzed by DFT calculations.

Late-transition-metal terminal oxo compounds: criticisms, analysis, and responses concerning the Pt-containing polyoxovanadate [H₂Pt^IVV₉O₂₈]⁵⁻ reported by Lee, Kortz, and their co-workers are presented. It is also deduced that a terminal platinum oxo compound from one of their groups, reported elsewhere but cited in connection with [H₂Pt^IVV₉O₂₈]⁵⁻, is miss-assigned.

The comments of Hill and co-workers regarding the platinum-containing polyoxovanadate [H₂Pt^IVV₉O₂₈]⁵⁻ are responded to by Kortz, Lee and co-workers. In addition, the existence of the anion α-[SiW₁₀Pt^IV₂O₄₀]⁸⁻ and the platinum oxo complex [OPt^IV(H₂O)(PW₉O₃₄)₂]¹⁶⁻ are discussed.

An extended family: The addition of microviridin B (see structure) and trunkamide to the ribosomal peptide biosynthetic family extends the molecular basis of posttranslational modifying reactions to include ω-ester/ω-amide linkage by ATP-grasp ligases (red) and prenylation. The discovery of these novel secondary metabolic reactions may presage the bioengineering of new antimicrobial peptide libraries.

Many routes to the destination: Cortistatins are steroids of marine origin of which cortistatin A has the highest antiangiogenetic action. Several total syntheses of this natural product have recently been achieved, based on biosynthesis, biomimetic synthesis, semisynthesis, and de novo synthesis, which are compared in this Highlight.

On the shoulders of giants: Lord Rutherford, who developed the theory of nuclear disintegration and a model of the nuclear atom, was lauded as one of the greatest scientists of all time. His research career witnessed the beginning of the atomic age, and his research group was a hotbed of talented, young scientists.

Long and winding road: The natural product azadirachtin (see figure) was first isolated in 1968 from the neem tree, and has been the focus of intense research efforts ever since. With numerous obstacles now overcome, the international efforts towards the total synthesis of this fascinating molecule have now achieved their long-standing goal.

A highly polar hypervalent S^IVS^II bond was formed in the synthesis of a sulfur-substituted sulfurane (see scheme), which was crystallographically characterized. Reduction of the 1,2-dithietane gives the corresponding thiol, and reoxidation gives the sulfurane by SS bond reformation. Thermal decomposition leads to a cyclic sulfenate and a thiirane.

Transition-metal-free hydrogenation of alkenes can be carried out with simple organocalcium catalysts (20 bar H₂, 20 °C). Both steps in the proposed catalytic cycle, hydride addition to the double bond and σ-bond metathesis with H₂, have been confirmed. Alkenes sensitive to polymerization are also hydrogenated in good yields.

Ipsoeasy: Cyclization of aryl radicals at the ipso-position of p-azido-substituted benzamides or 2-phenylacetamides results in effective production of spirocyclohexadieniminyl radicals through prompt elimination of molecular nitrogen by transient azidocyclohexadienyl radicals. The resultant iminyl radicals can be exploited for the synthesis of oxindoles or quinolones bearing spiro-cyclohexadienimine/cyclohexadienone rings (see picture, TTMSS=tris(trimethylsilyl)silane).

Branching out with sulfones: The use of allyl isopropyl sulfones solves the problem of premature isomerization and allows the radical addition of xanthates to α-branched allyl sulfones (see scheme; DCE=1,2-dichloroethane, TMS=trimethylsilyl). Highly functionalized structures can thus be rapidly assembled under mild reaction conditions by using cheap and readily available substrates and reagents.

In contrast to icosahedral carboranes, instead of deboration, 13-vertex carboranes undergo cage-carbon extrusion and cluster contraction to give icosahedral monocarborane anions on reaction with nucleophiles. In the proposed mechanism, nucleophilic attack on a cage carbon atom cleaves the C_cageC_cage bond, new C_cageB bonds form to preserve cluster integrity, and hydrogen migration generates the final icosahedral product (see scheme).

The bicycle works: A versatile route to the verticillane family of natural products has been devised, utilizing a strategically rigidified relay ring-closing metathesis reaction. The shape of the bicyclic product was used to stereoselectively control the bisepoxidation reaction towards hypoestoxide, a member of this natural product family.

Three-part harmony: Three-component Passerini reactions (P-3CR, see Scheme) of a wide range of aldehydes 2 and isocyanides 3, with hydrazoic acid 4 in toluene, in the presence of a [(salen)AlMe]-complex catalyst afford 5-(1-hydroxyalkyl)tetrazoles 1 in good-to-excellent yields and enantiomeric excess. A tandem Michael addition/enantioselective P-3CR, using an acrolein substrate, affords highly functionalized tetrazoles.

Selective recognition: The first efficient method for the kinetic resolution of racemic amino aldehydes (see scheme, PG=protecting group) is based on a copper(II)/(R,R)-Ph-BOX complex. The coordinated amino aldehydes were transformed into optically active amino acid methyl esters, and the non-coordinated amino aldehydes were converted into optically active amino aldehyde dimethyl acetals.

Highway to Heck: An efficient new one-pot palladium-catalyzed synthesis is described which affords a wide range of 9-fluorenone derivatives in good to excellent yields. A mechanism for the two distinct catalytic steps, CH bond activation followed by oxidative intramolecular Heck cyclization, is proposed and reaction intermediates supporting this mechanism have been isolated.

A reliable phosphonium-based PTC: For the first time a chiral quaternary tetraalkylphosphonium salt has successfully been used as a phase-transfer catalyst (PTC) for asymmetric amination of β-keto esters, in high yield and with high ee (see scheme). Asymmetric amination of a cyclic five-membered β-keto ester is a valuable method for preparing a key intermediate for asymmetric synthesis of aldose reductase inhibitor AS-3201 (Ranirestat).

Is ZnTe it great: Controlling the crystal-growth direction leads to formation of single-crystal ZnTe nanobelts along the 〈00〉 direction. The nanobelts, which were synthesized in oleylamine at 250 °C, have a narrow thickness (<6 nm). The ZnTe nanobelts behave as p-type semiconductors in field-effect transistors (see picture).

Lan-tastic! A lanthionine analogue of lacticin 3147 A2 (Lan-A2, 2) containing multiple thioether bridges (see picture) has been successfully synthesized by a combination of solid- and solution-phase peptide synthesis. Chemically synthesized Lan-A2 (2) exhibits synergistic biological activity similar to natural lacticin A2 (1) in the presence of natural lacticin A1 against Gram-positive bacteria.

Catching the worm: Long myelin-like tubules of a polyethylene oxide-polybutylene oxide block copolymer are kinetically unstable but can be trapped by silica incorporation to produce hybrid nanostructures with high shape anisotropy (see TEM image). Sequestration of mixtures of organosilanes and metal alkoxides or drug molecules in the polymer mesophase gives rise to a range of novel functional nanomaterials.

A magnetic coordination polymer, BBDTA⋅InBr₄, undergoes a spin-Peierls-like phase transition at 250 K. X-ray crystal analysis illustrates that the lattice dimerization accompanies elongation and contraction of the InN coordination bonds. Inhomogeneity of the spin and charge distribution on the organic radical increases progressively as the temperature decreases below the transition temperature.

Cluster's last stand: The hydrated gallium/indium nanocluster [Ga₇In₆(μ₃-OH)₆(μ-OH)₁₈(H₂O)₂₄(NO₃)₁₅] was prepared in a facile, high-yielding synthesis. The use of a key nitroso-containing organic compound as an additive allows for the isolation of multiple grams of the cluster. This larger-scale synthesis facilitates use of the cluster as a single-source precursor for effective thin-film transistors.

A new hierarchy: A supramolecular template strategy is used to synthesize hierarchical micro- and mesoporous metal–organic frameworks. The mesopore walls are constructed from a microporous framework (see picture). The porosity can be tuned by using different templates at various molar ratios.

A twisted mimic: Upon oxidation of [(μ-SCH₂C(CH₃)₂CH₂S-){Fe^I(CO)₂PMe₃}₂], rearrangement yields the mixed-valent Fe^IFe^II cation in a square-pyramid/inverted square-pyramid geometry with a semibridging CO ligand, closely mimicking the [FeFe] hydrogenase enzyme active site. According to de novo design principles, the steric effect of bridgehead bulk in the S–S bridging ligand stabilizes this structure in the absence of the protein matrix.

Shedding a light on the dark: Ultrafast electron diffraction of the tryptophan chromophore, indole (see determined structure; C orange, N blue, H white), reveals the involvement of dark structures in the nonradiative pathways of the isolated molecule. Such dark structures have to be part of the understanding of biological chromophore stability.

Ho ho ho! Characteristic visible and near-infrared (NIR) emission bands of the Pr^III and Ho^III complexes of the tetradentate 1-methyl-3-hydroxypyridin-2-one chromophore are observed in aqueous solution. The Ho^III complex has been structurally characterized and, for the first time for a Ho^III complex, the kinetics of the luminescence decay in the NIR region have been determined in solution.

Hollow nan': Hollow face-centered cubic (fcc) Co nanoparallelepipeds were prepared by thermolysis of solid fcc CoO nanoparallelepipeds in oleylamine (see TEM image). The solid fcc CoO nanoparallelepipeds are reduced by the oleylamine surfactant to form hollow fcc Co nanoparallelepipeds. Voids and fcc Co are generated on the surface of the solid fcc CoO nanoparallelepipeds by the removal of oxide as carbon monoxide.

Stealing C: Scattering of hyperthermal nitrogen ions from a D-ribose film efficiently abstracts carbon from the molecule to form CN (see scheme). The reaction is strongly bond and energy selective for C5 of D-ribose in its pyranose form. The sugar moiety of the DNA/RNA backbone will thus be a vulnerable point for damage caused by reactive scattering of secondary atomic nitrogen ions produced by energetic heavy ions.

Pure and porous: Several hundreds of square meters of enantiopure surface per gram of material were generated by introducing amino acids into periodically ordered mesoporous organosilica materials. The stereochemical nature of the surfaces was probed by measuring adsorption isotherms with chiral gases.

Small but more than enough: Proteins are detected in solution without additional amplification or labeling steps by using a small molecule as a reporter of the protein (see picture, Am-tag=amplification tag). The combination of self-assembled monolayers on gold with matrix-free laser desorption/ionization time-of-flight mass spectrometry offers ultrahigh sensitivity with a detection limit of several attomoles.

Reproducible switching of the polymorph-dependent excited-state intramolecular proton-transfer (ESIPT) luminescence of an imidazo[1,2-a]pyridine between blue-green and yellow (see picture) is achieved by thermal control of its solid-state molecular packing. Thus, ESIPT is a promising mechanism for packing-to-luminescence transduction and amplification that offers a novel design concept for tunable organic luminescent solids.

Open the cage: Symmetrical photoremovable bis-glutamate cages have been designed, synthesized, and characterized that can release a neurotransmitter with unprecedented two-photon efficiencies (see picture), up to 5 GM for BNSF–Glu (BNSF=2,7-bis-{4-nitro-8-[3-(2-propyl)-styryl]}-9,9-bis-[1-(3,6-dioxaheptyl)]-fluorene) at 800 nm, the optimal window both for tissue transparency and classically available laser sources.

Bi and N form a W: An acyclic Bi–N cation (synthesized as its GaCl₄⁻ salt) was prepared from lithium N,N′,N′-tris(trimethylsilyl)hydrazide and BiCl₃ by chloride abstraction. The W-shaped NNBiNN structure and the bonding of this deep blue cation, which can be regarded a bismapentazenium cation, is discussed on the basis of experimental and theoretical data.

It takes two: Both a lysine and a glutamate residue in the active site of tryptophan halogenase are essential for its chlorination activity. A mechanism for the regioselective enzymatic chlorination of tryptophan involving both amino acids is suggested (see scheme).

Copycat: An accurate synthetic model for Rieske type [2Fe-2S] cluster has been prepared that emulates structural and spectroscopic features of the natural protein sites, including the characteristic low g_av value in the EPR spectra of the reduced [2Fe-2S]⁺ species. The picture shows the crystal structure of the molecule (C gray, Fe red, N blue, S yellow), its EPR spectrum after reduction (bottom) and its Mössbauer spectrum (top).

Not like the others: A molecular palladium oxide cluster was formed by self-assembly of palladium(II) and arsenic(V) using mild reaction conditions. The resulting heteropolypalladate [Pd^II₁₃As^V₈O₃₄(OH)₆]⁸⁻ has a distorted cubic shape and edge lengths of about 1 nm. The thirteen Pd^II ions retain four-coordinate square-planar geometry, in marked contrast to all other known discrete polyoxometalates.

Without a transition metal, unsaturated organomagnesium compounds undergo homocoupling in the presence of a substoichiometric amount of the oxidant 2,2,6,6-tertramethylpiperidine-N-oxyl radical (TEMPO) and oxygen. Alkynyl Grignard reagents can even be coupled to give the corresponding diynes with dioxygen in the absence of a catalyst (see scheme).

Two breeds of cat: A palladium-catalyzed Suzuki cross-coupling and an enzymatic reduction with an alcohol dehydrogenase from Rhodococcus sp. together enable the efficient and highly enantioselective synthesis of chiral biaryl alcohols in a one-pot process (see scheme).

A change of the energy transfer mechanism (from contact quenching to FRET) increases the responsiveness of fluorescent hybridization probes. The communication between a responsive fluorescent base surrogate (see picture, green) and a near-infrared dye (red) in peptide nucleic acid provides probes that are extremely dark in the single strand. Hybridization furnishes strong fluorescence increase with a 200 nm shift in emission maximum.

The Trofimenko–Tebbe alliance: The sterically crowded, monoanionic scorpionate ligand Tp^tBu,Me provides a unique environment for the isolation of discrete rare-earth metal complexes with Y(CH₃){Al(CH₃)₄} and La(CH₂) moieties (see structure; C gray, H white, Al orange, B red, La pink, N blue); the latter shows promising reactivity as a Tebbe reagent analogue.

The specific binding of the cytohesin inhibitor SecinH3 to Sec7 domains of cytohesins was shown by the use of a bifunctional photoaffinity probe (see structure) on guanine nucleotide exchange factors (GEFs) and GTPases. This probe should be useful for the proteome-wide profiling of cytohesin complexes and the identification of the binding site.