Showing papers in "Angewandte Chemie in 1991"

Polyoxometalate Chemistry: An Old Field with New Dimensions in Several Disciplines

Abstract: Inorganic metal–oxygen cluster anions form a class of compounds that is unique in its topological and electronic versatility and is important in several disciplines. Names such as Berzelius, Werner, and Pauling appear in the early literature of the field. These clusters (so-called isopoly- and heteropolyanions) contain highly symmetrical core assemblies of MOx units (M = V, Mo, W) and often adopt quasi-spherical structures based on Archimedean and Platonic solids of considerable topological interest. Understanding the driving force for the formation of high-nuclearity clusters is still a formidable challenge. Polyoxoanions are important models for elucidating the biological and catalytic action of metal–chalcogenide clusters, since metal–metal interactions in the oxo clusters range from very weak (virtually none) to strong (metal–metal bonding) and can be controlled by choice of metal (3d, 4d, 5d), electron population (degree of reduction), and extent of protonation. Mixed-valence vanadates, in particular, show novel capacities for unpaired electrons, and the magnetic properties of these complexes may be tuned in a stepwise manner. Many vanadates also act as cryptands and clathrate hosts not only for neutral molecules and cations but also for anions, whereby a remarkable “induced self-assembly process” often occurs. Polyoxometalates have found applications in analytical and clinical chemistry, catalysis (including photocatalysis), biochemistry (electron transport inhibition), medicine (antitumoral, antiviral, and even anti-HIV activity), and solid-state devices. These fields are the focus of much current research. Metal–oxygen clusters are also present in the geosphere and possibly in the biosphere. The mixed–valence vanadates contribute to an understanding of the extremely versatile geochemistry of the metal. The significant differences between the chemistry of the polyoxoanions and that of the thioanions of the same elements is of relevance to heterogeneous catalysis, bioinorganic chemistry, and veterinary medicine.

Enantioselective Addition of Organometallic Reagents to Carbonyl Compounds: Chirality Transfer, Multiplication, and Amplification†

Abstract: Nucleophilic addition of organometallic reagents to carbonyl substrates constitutes one of the most fundamental operations in organic synthesis. Modification of the organometallic compounds by chiral, nonracemic auxiliaries offers a general opportunity to create optically active alcohols, and the catalytic version in particular provides maximum synthetic efficiency. The use of organozinc chemistry, unlike conventional organolithium or -magnesium chemistry, has realized an ideal catalytic enantioselective alkylation of aldehydes leading to a diverse array of secondary alcohols of high optical purity. A combination of dialkylzinc compounds and certain sterically constrained β-dialkylamino alcohols, such as (–)-3-exo-dimethylaminoiso- borneol [(–)-DAIB], as chiral inducers affords the best result (up to 99% ee). The alkyl transfer reaction occurs via a dinuclear Zn complex containing a chiral amino alkoxide, an aldehyde ligand, and three alkyl groups. The chiral multiplication method exhibits enormous chiral amplification: a high level of enantioselection (up to 98%) is attainable by use of DAIB in 14% ee. This unusual nonlinear effect is a result of a marked difference in chemical properties of the diastereomeric (homochiral and heterochiral) dinuclear complexes formed from the dialkylzinc and the DAIB auxiliary. This phenomenon may be the beginning of a new generation of enantioselective organic reactions.

A New Look at Electron Localization

Abstract: two-particle density for electrons of parallel spin, a function of two electrons’ coordinates (x, y , z and x’, y‘ , z‘) which gives the joint probability of finding one electron at position x , y , z and another electron of the same spin at position x’, y’ , z‘. The analysis showed that electrons of parallel spin restrict themselves to separate regions of space, and hence follows the notion of localized electron pairs. A well-known application of these concepts are the Gillespie and Nyholm

Metallomesogens: Metal Complexes in Organized Fluid Phases

Abstract: Metallomesogens, metal complexes of organic ligands which exhibit liquid crystalline (mesomorphic) character, combine the variety and range of metal-based coordination chemistry with the extraordinary physical properties exhibited by liquid crystals Thermotropic metallomesogens have been made incorporating many metals, including representatives of s-, p-, d-and even f-block elements Both rodlike (calamitic) and disklike (discotic) thermotropic metallomesogens are known, and examples of all the main mesophase types are found Many different varieties of ligand can be used: monodentate (4-substituted pyridines), bidentate (β-diketonates, dithiolenes, carboxylates, cyclometalated aromatic amines), or polydentate (phthalocyanines, porphyrins) As with organic mesogens, molecular shape and intermolecular forces play an important role, ie the ligands are important in determining mesophase character The chief requirement for a metallomesogen is a rigid core, usually unsaturated and either rod- or disklike in shape, bearing several long hydrocarbon tails The metal atom is usually at or near the center of gravity of the molecule In some cases the ligands are themselves mesogenic, but this is not a requirement The presence of one or more metals opens many exciting possibilities: new shapes, not easily generated by organic compounds, and hence new properties are then accessible The incorporation of d-block metals brings with it features such as color and paramagnetism Profound effects arise from the large and polarizable concentration of electron density that every metal atom possesses, since the molecular polarizability is a key factor in determining whether a molecule will form liquid crystals Enhanced physical properties (eg high birefringencies), as well as new and unexpected ones, will result A major requirement for metallomesogens to find applications in new device technology is that the metal–ligand bonds are strong and inert and the complexes stable; this can be accomplished with, for example, chelating ligands and the 5d metals

The Bioinorganic Chemistry of Vanadium

Abstract: Vanadium is a trace element that plays an important, perhaps essential and general role in the regulation of enzymatic phosphorylations Several forms of life, including the fly agaric toadstool (Amanita muscaria) and certain sea squirts (ascidians), are able to concentrate vanadium In other organisms vanadium is part of the active site of some enzymes Well-studied examples are the nitrogen-fixing bacterium Azotobacter and various seaweeds that use vanadate-dependent peroxidases to synthesize halogenated organic compounds Despite its importance as a “biometal” both in primitive, prokaryotic organisms (Azotobacter) and in the highly organized ascidians, which represent an early stage in the evolution of vertebrates, the bioinorganic chemistry of vanadium is still in its infancy Just as young, but undergoing explosive development, is the chemistry of model compounds for vanadium-containing biomolecules, a domain of the bioinorganic coordination chemist, who almost daily discovers compounds with new and surprising structural features This article reviews this fascinating area of bioinorganic chemistry

Chemie der Polyoxometallate: Aktuelle Variationen über ein altes Thema mit interdisziplinären Bezügen

Abstract: Die Verbindungsklasse der Metall-Sauerstoff-Clusteranionen ist nicht nur einzigartig hinsichtlich ihrer topologischen und elektronischen Vielfalt — sie hat auch erhebliche Bedeutung fur ganz unterschiedliche Disziplinen. So sind die fruheren Arbeiten auf diesem Forschungsgebiet mit Namen wie Berzelius, Werner und Pauling verbunden. Derartige Cluster (man nennt sie ublicherweise Isopoly- und Heteropolyanionen) enthalten haufig hochsymmetrische, oft angenahert kugelformige Anordnungen von MOx-Einheiten (z. B. M = V, Mo, W), und ihre Strukturen basieren haufig auf Archimedischen und Platonischen Korpern. Letztere sind von betrachtlichem topologischem Interesse. Noch wissen wir nicht, worin eigentlich die Triebkraft zur Bildung solcher polynuclearer Cluster besteht. Polyoxoanionen sind wichtige Modelle zum Verstandnis der biologischen und katalytischen Wirkung von Metall-Chalcogenid-Clustern, da die Metall-Metall-Wechselwirkungen von sehr gering (oder nicht vorhanden) bis stark (Metall-Metall-Bindungen) reichen konnen. Grundsatzlich lassen sich diese Wechselwirkungen durch die Wahl des Metalls (3d, 4d, 5d), durch Veranderung der Elektronenpopulation (Grad der Reduktion) und den Umfang der Protonierung beeinflussen. Gemischtvalente Vanadate konnen beispielsweise nacheinander mehrere Elektronen ohne Spinpaarung aufnehmen, d.h. die magnetischen Eigenschaften dieser Komplexe lassen sich schrittweise uber einen weiten Bereich variieren. Viele Vanadate wirken als Cryptanden oder Clathrat-Wirte fur Neutralmolekule und Kationen, und, was neu ist, auch fur Anionen, wobei meistens ein bemerkenswerter „induzierter Selbstorganisationsprozes” ablauft. Anwendung finden Polyoxometallate in der Analytischen und Klinischen Chemie, in der Katalyse (einschlieslich Photokatalyse), in der Biochemie (Inhibierung von Elektronentransfer-Prozessen), in der Medizin (antitumorale, antivirale und sogar anti-HIV-Aktivitat) und bei der Herstellung von integrierten Schaltungen, alles Gebiete von aktuellem Interesse. Metall-Sauerstoff-Cluster treten auch in der Geosphare — die gemischtvalenten Vanadate ermoglichen ein Verstandnis der uberaus vielfaltigen Geochemie dieses Metalls — und moglicherweise auch in der Biosphare auf. Zwischen der Chemie der Polyoxoanionen und der Thioanionen derselben Elemente bestehen wichtige Unterschiede, die fur die heterogene Katalyse, die Bioanorganische Chemie und die Veterinarmedizin von Bedeutung sind.

1,4-Dihydropyridines: Effects of Chirality and Conformation on the Calcium Antagonist and Calcium Agonist Activities

Abstract: 4-Aryl-l,4-dihydropyridine-3,5-dicarboxylic diesters of the nifedipine type have become almost indispensable for the treatment of cardiovascular diseases since they first appeared on the market in 1975. There are some twenty derivatives currently under clinical development worldwide and work in this area is continuing undiminished. The 1,4-dihydropyridines are the most effective of the calcium antagonists or calcium channel blockers. They are valued not only for their pharmacological effect, but also as a tool for the investigation of the calcium channel, particularly since the discovery that this class also includes compounds that have exactly the opposite action profile and are known as calcium agonists. There are even instances in which this reversal of activity is found between enantiomers. In view of the importance of chirality to pharmacological activity, the present article will describe methods for the separation of enantiomers, point out the structural differences between calcium antagonists and calcium agonists, and attempt to explain the difference in their behavior.

Structure and Molecular Stacking of Anthocyanins—Flower Color Variation

Abstract: In 1913 Willstatter made the striking observation that the same pigment can give rise to different colors. Thus, the same pigment, cyanin, is found in the blue cornflower and in the red rose. Willstatter attributed the variety of flower colors to different pH values in solution. Indeed, anthocyanin changes its color with pH; it appears red in acidic, violet in neutral, and blue in basic aqueous solution. Willstatter's pH-theory for explaining flower color variation is still to be found in major text books of organic chemistry. Very recently, however, reinvestigation has disclosed that the color variation and stabilization of anthocyanins in aqueous solution could have other causes, namely self-association, copigmentation and intramolecular sandwich-type stacking. The stacking would be mainly brought about by intermolecular or intramolecular hydrophobic interaction between aromatic nuclei such as anthocyanidins, flavones and aromatic acids. In addition, hydrogen bonds and charge transfer interactions may also be involved. The most interesting molecular complexes of anthocyanins are the metalloanthocyanins such as commelinin and protocyanin (blue cornflower pigment). These seemingly pure blue complexes each consist of six anthocyanin and six flavone molecules and two metal ions; their molecular weight is nearly 10000. A structure is proposed for commelinin.

Chemically Modified Oligonucleotides as Probes and Inhibitors

Abstract: Oligonucleotides bind specifically to single-stranded nucleic acids to form a double helix if there is a complementary antiparallel nucleotide sequence. In addition, certain oligonucleotides bind specifically to a variety of proteins. Therefore, biological processes involving these nucleic acids or proteins can be modulated (normally inhibited) by addition of the respective oligonucleotides. The effects of these oligonucleotides and the fields of potential application can be broadened by the introduction of chemically modified nucleotides. For instance, replacing oligonucleotide phosphate groups by methylphosphonates results in the loss of one negative charge per nucleotide and the oligonucleotide becomes more lipophilic. An oligonucleotide carrying a reactive group can modify its binding partner. An oligonucleotide covalently linked to a dye can be localized in a biological specimen. Oligonucleotides attached to an enzyme can be detected in very small amounts since the enzyme can catalyze the formation of large amounts of the substance assayed (e.g., a fluorescent product). An important biochemical application is the detection and localization of a messenger RNA or its gene. Medical applications include the detection of bacterial or viral sequences. There is also great interest in inhibiting the translation of messenger RNA and the transcription and replication of DNA. So-called antisense oligonucleotides are currently being used for the inhibition of protein biosynthesis and of reverse transcription of retroviruses.

Transition‐Metal Thiolates: From Molecular Fragments of Sulfidic Solids to Models for Active Centers in Biomolecules

Abstract: Thiolates are presently a subject of great interest in the chemistry of complexes involving transition-metal elements and soft ligands. The manifold electronic and steric capabilities offered by the monodentate ligands RS⊖ and the bidentate chelate ligands ⊖SRS⊖ have been used to stabilize a broad spectrum of mononuclear, oligomeric, and polymeric complexes with new and remarkable structures and properties. Impetus has especially been provided by the synthesis of polynuclear cagelike homo- and heteroleptic metal–sulfur frameworks, which can often be regarded as “molecular fragments” of the structures of inorganic sulfides. Thiolates and mixed sulfide-thiolates of the late open- and closed-shell 3d metals (Fe, Co, Ni, Cu, Zn) and some of their homologues (Au, Cd, Hg), as well as of Mo, are of particular importance as model complexes for biologically important metal centers coordinated by sulfur. They have played an important role in increasing our understanding of the structure, bonding, and function of the reactive centers in ferredoxins, rubredoxins, nitrogenases, blue copper proteins, metallothioneins, and antiarthritic drugs.

Lantibiotics—Ribosomally Synthesized Biologically Active Polypeptides containing Sulfide Bridges and α,β‐Didehydroamino Acids

Abstract: Lantibiotics are polycyclic peptide antibiotics containing intrachain sulfide bridges, formed from the thioether groups of the amino acids lanthionine and β-methyllanthionine. They also contain α,β-unsaturated amino acids such as didehydroalanine and didehydroaminobutyric acid. A knowledge of the lantibiotic biosynthetic steps and the enzymes involved makes possible a gene technological construction of analogous highly modified polypeptides. To the family of lantibiotics belong nisin, an important food preservative, epidermin, a highly specific therapeutic agent against acne, a series of enzyme inhibitors, as well as immunologically interesting active peptides. Lantibiotics are produced by ribosomal synthesis, starting from inactive precursor proteins (prelantibiotics). The latter are post-translationally converted into the active peptide antibiotics through enzymic modifications. The modifying enzymes effect dehydrations at the serine and threonine residues and stereospecific additions of the cysteine thiol groups to the resulting α,β-unsaturated double bonds, which lead to the formation of several sulfide bridges. Upon subsequent proteolytic cleavage of the leader peptide, the biologically active lantibiotic is formed. Conformational analyses of the lantibiotics, as well as of their prepeptides, enables one to obtain information about the mechanism and steps of the biosynthesis. Antibodies against synthetic prepeptide sequences, and modern instrumental methods for the analysis of peptides, allow structural elucidation of the biosynthetic intermediates.

Towards the Chemical Synthesis of Proteins

Abstract: The chemical total synthesis of proteins using solid supports has made great progress. It is therefore becoming a reality what E. Fischer already predicted in 1902: “I foresee the time when physiological chemistry… is able to prepare synthetic enzymes.” The synthesis of peptides of up to 20 amino acids by the well-established solid-phase procedure on polymeric supports (SPPS) has made great progress through the development of newer supports. At the same time, methods have emerged which facilitate the separation and characterization of peptides, thus allowing optimization of the synthesis of pure materials. The new supports which enable one to synthesize peptides by a rapid continuous flow procedure are characterized by hydrophilicity, beads of approximately equal size, similar swelling properties in the solvents used for peptide synthesis, and stability at high pressure. With graft copolymers of weakly cross-linked polystyrene and linear polyethylene glycol (PEG), the synthetic cycle for coupling of one amino acid can routinely be reduced to 10–20 min with a concomitant higher yield. With beads of monodispersed graft copolymer of 10 μm diameter, a synthetic cycle can, in principle, be shortened to 1–5 min. By utilizing this high-speed solid-phase procedure, larger peptides up to the size of proteins could also be prepared in a few hours. With newer mass spectroscopic methods such as ion-spray mass spectrometry, peptides of up to a molecular mass of 100 kDa can be characterized, and with the advent of capillary electrophoresis, another very efficient separation tool, besides HPLC, is at our disposal.

The Isoinversion Principle—a General Model of Chemical Selectivity

Abstract: A large number of successful methods for chirality transfer, using either stoichiometric or catalytic chiral auxiliaries, are in use today. However, there is a lack of practical and dynamic selectivity models, i.e. models which take into account the entire reaction sequence, and which allow simple and reliable assessment, optimization and prediction of selectivity in asymmetric syntheses. The models that are available are either too strongly biased to the steric requirement of the particular molecules reacting, but do not go beyond classical considerations of static facial differentiation, or they take a demanding, theoretical approach, which because of its inherent limitations and the great theoretical effort required has not yet found its way into the practical world of the synthetic chemist. The “Isoinversion Principle”, developed on the basis of Eyring's theory, closes this gap. With its aid, the synthetic chemist can determine the characteristic isoinversion temperature Ti for the reaction type of interest from a few temperature-dependent measurements of selectivity parameters. Ti then affords information on interesting questions such as optimization etc. The advantage of this method is that it is useful not only for stereoselectivity, but for any kind of process where selectivity in general (regio-,chemo-, etc) is generated at two or more stages of a reaction sequence, regardless of whether these reactions involve the ground state or a diabatic photoprocess. The present review will demonstrate that this generation of selectivity at two or more stages of a reaction sequence occurs more commonly than is generally thought.

The Logic of Chemical Synthesis: Multistep Synthesis of Complex Carbogenic Molecules (Nobel Lecture)†

Abstract: Carbogens, members of the family of carbon-containing compounds, can exist in an infinite variety of compositions, forms and sizes. The naturally occurring carbogens, or organic substances as they are known more traditionally , constitute the matter of all life on earth, and their science at the molecular level defines a fundamental language of that life. The chemical synthesis of these naturally occurring carbogens and many millions of unnatural carbogenic substances has been one of the major enterprises of science in this century. That fact is affirmed by the award of the Nobel Prize in Chemistry for 1990 for the \" development of the theory and methodology of organic synthesis \". Chemical synthesis is uniquely positioned at the heart of chemistry, the central science, and its impact on our lives and society is all pervasive. For instance, many of today's medicines are synthetic and many of tomorrow's will be conceived and produced by synthetic chemists. To the field of synthetic chemistry belongs an array of responsibilities which are crucial for the future of mankind, not only with regard to the health, material and economic needs of our society, but also for the attainment of an understanding of matter, chemical change and life at the highest level of which the human mind is capable. The post World War II period encompassed remarkable achievement in chemical synthesis. In the first two decades of this period chemical syntheses were developed which could not have been anticipated in the earlier part of this century. For the first time, several very complex molecules were assembled by elaborately conceived multistep processes, for example vitamin A followed by an equally dramatic scientific advance during the past three decades, in which chemical synthesis has been raised to a qualitatively higher level of sophistication. Today, in many laboratories around the world chemists are synthesizing at an astonishing rate complex carbogenic structures which could not have been made effectively in the 1950's or early

New Approaches to the Use of Amino Acids as Chiral Building Blocks in Organic Synthesis [New Synthetic Methods (85)]

Abstract: α-Amino acids protected at nitrogen in quite different ways can be transformed without racemization into the corresponding α-amino aldehydes. Provided one chooses the right protecting groups (e.g., two benzyl residues on nitrogen) it is possible for the first time to carry out Grignard-like, aldol, and Me3SiCN additions, and hetero-Diels–Alder reactions with a high degree of nonchelation control. If the reactions of classical carbanions turn out to be nonselective, transmetalation, for example into organotitanium reagents, constitutes an important tool in controlling stereoselectivity. Diastereoselectivity can be reversed by specific variation of the protecting group and reagent. “Protecting-group tuning”, “metal tuning”, and “ligand tuning” are very useful in reactions of α-amino aldimines as well. The α-amino aldehydes can also be converted by Wittig reactions into electron-poor γ-amino olefins, which in turn undergo stereoselective cuprate, Michael, and cycloadditions.

Strained‐Ring and Double‐Bond Systems Consisting of the Group 14 Elements Si, Ge, and Sn

Abstract: The organometallic chemistry of the Group 14 elements E = Si, Ge, Sn in the 1980's is highlighted by the successful construction and characterization of three systems previously thought to be too reactive to exists: (1) three-membered ring compounds including cyclotrisilane, cyclotrigermane, and cyclotristannane, (2) molecules containing EE double bonds including disilene, digermene, and distannene, and (3) strained polycycles containing a skeleton of Group 14 elements, such as bicyclo[1.1.0]tetrasilane, hexagemaprismane, and octasilacubane. The majority of these numerous compounds now available are fully substituted with bulky ligands to suppress the reactivity intrinsic to the systems. These compounds permit examinations of (1) the variation of physical and chemical properties of a system with these elements and also with the ligands and (2) how two systems are interrelated thermally and photochemically with the intermediacy of the divalent (carbene-like) species. Theoretical calculations on virtually all of the parent compounds discussed in this review are evaluated alongside the experimental results. Some polycycles may constitute a stepping-stone on the way to compounds with a triple bond.

Bonding Patterns in Intermetallic Compounds

Abstract: Intermetallic phases have long been among the black sheep in the family of chemical compounds. Their chemical bonding has eluded description by the valence rules, which otherwise are extremely effective. As a result, understanding of the structure–bonding relationships in these phases to date has remained nebulous, even though they form the largest group of inorganic compounds. Their broad industrial applicability and richly varied structural chemistry call for new approaches for explaining their structures, electronic structures, and physical properties. A combination of new experimental and theoretical investigations has revealed interesting local aspects of chemical bonding in metals and thereby pointed to a route from the valence compounds, through the cluster and electron-deficient compounds, to the intermetallic phases.

Enantioselektive Addition von Organometallreagentien an Carbonylverbindungen: Übertragung, Vervielfältigung und Verstärkung der Chiralität

Abstract: Die nucleophile Addition von Organometallreagentien an Carbonylverbindungen ist eine der grundlegendsten Operationen der Organischen Synthese. Eine Modifizierung der Organometallkomponente durch chirale, nichtracemische Hilfsstoffe eroffnet einen allgemeinen Zugang zu optisch aktiven Alkoholen, wobei im besonderen die Leistungsfahigkeit der katalytischen Variante beeindruckend ist. Anders als die herkommlichen Organolithium- oder Organomagnesiumreagentien ermoglichten Organozinkverbindungen eine ideale katalytische enantioselektive Alkylierung von Aldehyden, die zu einer breiten Palette von sekundaren Alkoholen hoher optischer Reinheit fuhrte. Die besten Ergebnisse (bis zu 99% ee) liefert eine Kombination von Dialkylzinkverbindungen mit bestimmten sterisch uberfrachteten β-Dialkylaminoalkoholen wie (—)-3-exo-Dimethylaminoisoborneol [(—)-DAIB] als Trager der Chiralitatsinformation. Die Alkylubertragung verlauft uber einen zweikernigen Zinkkomplex, der ein chirales Aminoalkoxid, den Aldehyd und drei Alkylreste als Liganden enthalt. Die Methode der Chiralitatsvervielfaltigung ermoglicht eine enorme Chiralitatsverstarkung. So kann durch Einsatz von (—)-DAIB mit 14% ee eine Enantioselektion bis zu 98% erzielt werden. Dieser ungewohnliche nichtlineare Effekt kann darauf zuruckgefuhrt werden, das sich die diastereomeren (homochiralen und heterochiralen) zweikernigen Komplexe aus Dialkylzinkverbindung und dem Hilfsstoff DAIB in ihren chemischen Eigenschaften stark unterscheiden. Moglicherweise markiert dieses Phanomen den Beginn einer neuen Generation enantioselektiver organischer Reaktionen.