Angewandte Chemie International Edition

Human DNA topoisomerase II is inhibited in vitro by acutissimin A, a flavano-ellagitannin, with an activity much higher than that of the clinically used antitumor drug etoposide. Acutissimin A is formed by a non-enzymatic, yet diastereoselective, condensation reaction occurring during the aging of red wine in oak barrels. S. Quideau et al. report its high-yielding semi-synthesis in their Communication on page 6012 ff.

Imagine… if the biomachinery of nature accepted every uncoded amino acid site-specifically as desired. Spectacular advances in breaking the genetic code to expand the set of amino acids available for protein biosynthesis are highlighted, and examples of the post-translational chemical modification of proteins containing these nonnatural amino acids are presented (see scheme).

Optimization of synthesis methods for carbon nanotubes is an essential requirement for realizing their potential applications in field-emission devices, (bio)sensors, or as electrical interconnections in microchips. Procedures directly yielding clean nanotubes from a single molecular precursor (see picture) are highly desired and are expected to provide important clues to the general mechanism of nanotube formation.

A radical view of oxygenation: As revealed by recent research, radical intermediates are almost ubiquitous during metal-assisted oxo-functionalizations of organic substrates (see picture). This review covers examples from the areas as diverse as homogeneous and heterogeneous chemistry, as well as metalloenzyme systems.

Microwave magic: GC–MS analysis and quantum chemical calculations were used to show that N₂(SiCl₃)₄ was a product of the reaction of SiCl₄ with N₂ activated with a gas plasma generated by microwaves. N₂(SiCl₃)₄ is the first known perhalogenated silyl hydrazine (see scheme: N blue, Si gray, Cl green).

A mechanistic puzzle in the field of osmium(VIII)-mediated functionalization of olefins: How do the diaminations of olefins to give osmaimidazolidines with a stereogenic osmium center proceed (see scheme: C: gray, N: green, red: O, Os: pink)?

The core of the problem: The selective hydroxylation of benzylic CH bonds by a [Cu₂O₂]²⁺ core is a nonsynchronous concerted process (see scheme). This is the result of density functional calculations on the mechanistic scenario of the monooxygenase reactivity of a bis(μ-oxo)dicopper(III) complex.

The metathesis catalyst 1 allows the first living cyclopolymerization of 1,6-heptadiynes. With the chiral 4-(ethoxycarbonyl)-4-(1S,2R,5S)-(+)-menthoxycarbonyl-1,6-heptadiyne highly tactic polymers with an alternating cis–trans structure and a stereoregularity of greater than 95 % are obtained. Fixation of 1 on poly(2-oxazoline) block copolymers provides access to poly(acetylene)s under aqueous conditions by micellar catalysis.

A semiautomated high-throughput system has been developed to express and purify proteins and assay their catalytic activity. The screen can be used to evolve activity, selectivity, and expression levels of proteins directly or in combination with selections. To illustrate its potential, the system was applied to the directed evolution of catalytic antibodies with aldolase activity.

Stacking the deck: A series of aromatic fluorinated nucleosides (the electrostatic surface potentials are depicted) was used to probe electrostatic effects in the stacking of DNA bases in water. Although increasing fluorine substitution (from zero through five) generally increases stacking ability, a new tetrafluorinated analogue is, surprisingly, the strongest helix stabilizer, while the pentafluorinated base is the weakest.

Running rings around ammonium: Use of amine templates leads to a rich structural chemistry for heterometallic cyclic compounds. For example, use of two diethylammonium cations leads to the formation of the {Cr₁₀Cu₂} cage, which is stabilized by NH⋅⋅⋅F bonds (see picture). The results suggest a new method for making sophisticated polymetallic architectures.

Organolanthanides with amido-tethered N-heterocyclic carbenes: a new bidentate ligand that tethers an N-heterocyclic carbene group to a trivalent lanthanide complex (samarium, depicted, N′′=N(SiMe₃)₂; or yttrium) affords the first organolanthanide amido–carbene complexes and an opportunity to explore the strength and reactivity of the early metal–N-heterocyclic carbene fragment.

Blue lights the way! The rapid evaluation of enantiomeric excess in the high-throughput screening of libraries has been a hurdle to the discovery of effective catalysts. A blue-fluorescent monoclonal antibody (mAb) addresses this problem; mAb 19G2 is used as a fluorescent sensor (see picture) to evaluate a panel of Cinchona alkaloid derivatives in the synthesis of asymmetric amino acids by phase-transfer catalysis.

A potential general approach to potent N-heterocyclic glycosidase inhibitors is illustrated by the first total synthesis of (+)-broussonetine G (1). The key transformation of the synthesis relies on two successive palladium-catalyzed asymmetric allylic alkylations of butadiene monoxide with a nitrogen nucleophile to construct the pyrrolidine core.

Sterically protected tri- and hexanuclear platinum clusters were used as building blocks for the high-yield synthesis of a first-generation dendrimer (see picture; tBu groups are omitted for clarity), which is chemically and thermally stable, and in which the cluster units are separated by conjugated 1,3,5-triethynylphenyl groups.

Less catalyst, lower temperature, and greater generality are the advantages of the new general protocol over those previously described for the palladium-catalyzed coupling of aryl chlorides and alkynes (see scheme). Better results are obtained without a copper cocatalyst, which has been found to inhibit product formation in the coupling reaction of aryl chlorides with terminal alkynes.

An entirely substrate-controlled total synthesis of three members of the thapsigargin family (e.g. trilobolide) is achieved starting from (S)-carvone. The synthesis is linear in nature but is achieved in high yield (>90 % per step). The route permits late-stage divergence, providing access to a range of natural products and structural analogues.

Catalytic building blocks: Chiral porous zirconium phosphonates containing Ru-binap moieties are synthesized by a molecular building-block approach, and characterized by a variety of techniques. These hybrid solids are used for enantioselective heterogeneous asymmetric hydrogenation of β-keto esters with ee values of up to 95 % (see picture). Ready tunability of such a molecular building-block approach promises to lead to useful heterogeneous asymmetric catalysts.

Two types of aromaticity: Experimental and theoretical evidence shows that eight- and nine-atom boron clusters are perfectly planar molecular wheels, with a hepta- or octacoordinated central boron atom, respectively (see picture, B green). The radii of the miniature molecular wheels are found to be 1.8 and 2.0 Å. Analyses of their chemical bonding reveal that they possess double (σ and π) aromaticity, which is responsible for the wheel structures and the extreme coordination environments.

Copper(II)-based complex catalysts (see crystal structures) were prepared and characterized by X-ray crystallography. They were shown to be active catalysts for asymmetric oxidative coupling of 2-naphthol with high enantioselectivity.

Good health! Although not initially present in red wine, acutissimin A (see picture) and other flavano-ellagitannins are formed during aging in oak barrels by a diastereoselective nonenzymatic condensation reaction between flavan-3-ols present in grapes and ellagitannin vescalagin from oak. Acutissimin A is a DNA topoisomerase inhibitor that is 250-fold more potent in vitro than the clinically used anicancer drug etoposide.

In a supermolecular system, the sum of properties is more than that of the individual components. The combination of rod and disc shaped groups (see picture) in the right ratio allows the design of a material with nematic and several layered (smectic) phases. Shape-induced nanophase segregation of rods and discs leads to the formation of distinct sublayers.

Taking the temperature: The electronic properties of DNA largely depend on the orientation of the π stacking. Based on the discrete clusters of interstrand four-base π stacks in Z-form DNA, a molecular thermometer that exploits the differences in the π stackings of B- and Z-DNA has been designed (see picture).

The tubular secondary structure of a folded helical polymer—a poly(m-phenyleneethynylene) derivative carrying multiple cinnamate moieties—is stabilized by intramolecular cross-linking through topochemically controlled photodimerizations (see schematic representation). This approach should enable the generation of organic nanotubes with controlled dimensions and surface functionality that constitute attractive building blocks for functional nanostructures.