Showing papers in "Topics in Current Chemistry in 1999"

Immobilized Enzymes: Methods and Applications

Abstract: Immobilized enzymes are used in organic syntheses to fully exploit the technical and economical advantages of biocatalysts based on isolated enzymes. Immobilization enables the separation of the enzyme catalyst easily from the reaction mixture, and can lower the costs of enzymes dramatically. This is true for immobilized enzyme preparations that provide a well-balanced overall performance, based on reasonable immobilization yields, low mass transfer limitations, and high operational stability. There are many methods available for immobilization which span from binding on prefabricated carrier materials to incorporation into in situ prepared carriers. Operative binding forces vary between weak multiple adsorptive interactions and single attachments through strong covalent binding.Which of the methods is the most appropriate is usually a matter of the desired applications. It is therefore the intention of this paper to outline the common immobilization methods and reaction technologies to facilitate proper applications of immobilized enzymes.

Principles of Fullerene Reactivity

Abstract: The fullerenes have been established as new and versatile building blocks in organic chemistry. A large number of fascinating fullerene derivatives, especially of the icosahedral buck-minsterfullerene C60, have been synthesized. The chemistry of C60 continues to be good for many surprises. However, based on present knowledge a series of reactivity principles can be deduced which makes derivatization of this all carbon cluster more and more predictable. In this article first the geometric and electronic properties of the parent molecule are analyzed. The bent structure of the carbon network C60 and the filling of its molecular orbital with 60 π-electrons dictate the chemical reactivity. A very important aspect that was introduced with the investigation of fullerene chemistry is the shape dependence of reactivity.

Nanotubes: A Revolution in Materials Science and Electronics

Abstract: Nanotube theoretical and experimental research has developed very rapidly over the last seven years, following the bulk production of C60 and structural identification of carbon nanotubes in soot deposits formed during plasma arc experiments. This review summarises achievements in nanotube technology, in particular various routes to carbon nanotubes and their remarkable mechanical and conducting properties. The creation of novel nanotubules, nanowires and nanorods containing other elements such as B, N, Si, O, Mo, S and W is also reviewed. These advances are paving the way to nanoscale technology and promise to provide a wide spectrum of applications.

An introduction to the theory of geminals

Abstract: Two-electron functions, called also geminals, have been around in quantum chemistry for some time. They represent a generalization of one-electron orbitals accounting for intra-orbital correlation effects. Geminal-based methods can be tailored to be variational as well as size-consistent and size-extensive. In spite of these appealing features, geminals became somewhat eclipsed in modern quantum chemistry because of their relative complexity and because the associated energies do not always cover a sufficient fraction of the correlation energy. However, several recent investigations revisit geminals and advocate the use of some extended geminal models which may turn out to offer useful alternatives to conventional approaches. In this paper, the formalism of two-electron functions will be reviewed in a simple fashion, focusing mainly on qualitative and conceptual points rather than technical details. After a short historical survey, the basic notions of geminals will be reviewed both in first- and second-quantized notations, the latter being especially advantageous when dealing with geminals. A few important points about the optimization of geminal-based wave functions will then be discussed, followed by a discussion about the inherent connection between geminals and the localization problem. We shall close with a few remarks on the prospect of geminal theories.

Solvent-free Reactions

Abstract: For reasons of economy and pollution, solvent-free methods are of great interest in order to modernize classical procedures making them more clean, safe and easy to perform. Reactions on solid mineral supports, reactions without any solvent/support or catalyst, and solid-liquid phase transfer catalysis can be thus employed with noticeable increases in reactivity and selectivity. A comprehensive review of these techniques is presented here. These methodologies can moreover be improved to take advantage of microwave activation as a beneficial alternative to conventional heating under safe and efficient conditions with large enhancements in yields and savings in time.

Superior Biocatalysts by Directed Evolution

Abstract: Useful biocatalysts for organic chemistry can be created by directed evolution.Mutations are introduced into genes encoding biocatalyst proteins of interest by error-prone PCR or other random mutagenesis methods. The mutated genes can be rearranged by recombinative processes like DNA shuffling, thereby significantly enhancing the efficiency with which genes can be evolved. These genes are expressed in suitable microbial hosts leading to the production of functional biocatalysts. Selection or screening procedures serve to identify in a large library of potential candidates the biocatalyst which possesses the desired properties. Examples of applications include subtilisin E with greatly improved catalytic activity and stability in organic solvent, an esterase with 50-fold higher activity in organic solvent, and a β-lactamase conferring a 32,000-fold increased antibiotic resistance. Furthermore, directed evolution of a bacterial lipase resulted in a significant increase in enantioselectivity,thereby demonstrating the enormous potential of this process for organic chemistry.

Macrocyclic Oligo(phenylacetylenes) and Oligo(phenyldiacetylenes)

Abstract: The following is a comprehensive survey of the chemistry of macrocycles comprised entirely of phenyl and acetylenic moieties. Although over four decades old, this area of research has come into its own just in the last few years. Widespread interest in the field has been spurred by recent discoveries utilizing these compounds as ligands for organometallic chemistry, hosts for binding guest molecules, models of synthetic carbon allotropes, and precursors to fullerenes and other carbon-rich materials. This review will discuss the preparation of a tremendous variety of novel structures and detail the development of versatile synthetic methods for macrocycle construction.

Water as Solvent in Organic Synthesis

Abstract: Organic reactions using water as solvent are reviewed with a focus on pericyclic reactions, carbonyl additions, stoichiometric organometallic reactions, oxidations and reductions which show an unusual outcome in terms of reactivity and selectivity compared with those performed in organic solvent. The advantages of using water as a solvent are discussed and related to the hydrophobic effects and the hydrogen-bonding ability of water with a special emphasis on its very high cohesive energy density which strongly favors organic reactions having a negative activation volume.

Ring Opening Reactions of Fullerenes: Designed Approaches to Endohedral Metal Complexes

Abstract: Endohedral complexes of fullerenes are some of the most attractive targets of research in fullerene chemistry and physics. An overview of the field is provided with a focus on endohedral complexes incorporating lanthanide metals, noble gases, and atomic nitrogen. Although the present approaches have been successful in providing the first members of this class of fullerenes, their preparation is still difficult and limited to a few elements. It is argued that ring opening reactions within fullerene shells have the potential to provide easy access to endohedral metallofullerenes on a large scale, including those with transition metals which are potentially the most interesting elements in regard to their materials properties. Current ring opening reactions within fullerene shells are reviewed. An outlook on ring opening reactions leading to effectively large apertures is presented.

Oxynitrilases: From Cyanogenesis to Asymmetric Synthesis

Abstract: Oxynitrilases are enzymes which catalyse the formation and cleavage of cyanohydrins. The cyanohydrin formation reaction proceeds by stereoselective addition of hydrogen cyanide to aldehydes or ketones to give enantiopure α-hydroxynitriles. This simple method of C-C bond formation has become a promising method to obtain a number of biologically active compounds. Cyanohydrin fission plays an important role in nature and is involved in plant defence where hydrogen cyanide is liberated upon plant damage. Among the known oxynitrilases only the (R)-oxynitrilase from Prunus amygdalus and the (S)-oxynitrilases from Hevea brasiliensis and Manihot esculenta are available in sufficient quantities which allow cyanohydrin formation on a larger scale. Prunus amygdalus oxynitrilase can easily be isolated from natural sources (bitter almond bran) and for two (S)-oxynitrilases functional overexpression allows their production in sufficient amounts for broad preparative applications. The three dimensional structure of the (S)-oxynitrilase from Hevea brasiliensis has been determined, and suggestions concerning the reaction mechanism have been discussed. Several procedures employing oxynitrilases have been developed to date which enable cyanohydrin formation on a preparative scale, particularly the use of buffer solutions as the reaction medium, organic solvents with immobilised enzymes, as well as biphasic reaction systems. Possible follow up reactions of the generated hydroxy and nitrile functionality, as well as the conversion of unsaturated cyanohydrins into valuable asymmetric compounds are outlined.

Oligo- and Polyarylenes, Oligo- and Polyarylenevinylenes

Abstract: An important challenge in the design of novel conjugated polymers is the synthesis of materials with tailor-made solid-state electronic properties. This section outlines the synthesis of the most significant classes of poly(para-phenylenevinylene)s (PPVs),poly(para-phenylene)s (PPPs), and related structures. Furthermore, this review demonstrates that the chromophoric and electronic properties of conjugated π-systems are sensitive to their molecular and supramolecular architecture.

Thiocarbonyl Compounds as Specific Tools for Organic Synthesis

Abstract: Thiocarbonyl compounds (thioamides, thioesters, thioketones...) react readily with a large variety of reagents (nucleophiles, electrophiles and radicals) due to their weak C=S bond and the aptitude of sulfur to stabilise an adjacent charge or radical centre. Thus, nucleophilic additions, deprotonation, and sigmatropic rearrangements are often more facile than in the oxygen series. Moreover, a number of specific reactions have been uncovered: thiophilic addition of nucleophiles, Michael addition of enethiolates, the Eschenmoser reaction, oxidation to sulfines, a large variety of [4+2] and [3+2] cycloaddition reactions with 1,3-dienes and 1,3-dipoles. Far from being purely exotic species, thiocarbonyl compounds are now efficient and specific tools and have indeed been used in multi-step synthetic schemes leading to various products of biological interest.

Sulfur Radical Cations

Abstract: Sulfur radical cations are novel reaction intermediates that have attracted considerable attention recently. This in part is due to the renewed interest in the chemistry of radical cations in general, as well as four other factors. The first is the basis for understanding the structure and reactions of radical cations — can their inherent nature be best depicted by analogy with radicals, with cations, or is a new algorithm required? As is exemplified in this review, sulfur radical cations show novel behavior. Second, some reactions of sulfur radical cations are attracting interest for their application in organic synthesis. Third, biological electron-transfer may be mediated by sulfur and, indeed, sulfur radical cations may be intermediates in biological redox processes. Finally, materials based on tetrathiafulvalene, polythiophene, and related sulfur compounds have high electrical conductivity which may be understood in terms of p-delocalized sulfur radical cations or the related dications. Consequently, a comprehensive and critical review of this field appeared timely.

Benzotrifluoride and Derivatives: Useful Solvents for Organic Synthesis and Fluorous Synthesis

Abstract: Benzotrifluoride (BTF, trifluoromethylbenzene, α,α,α-trifluorotoluene, C6H5CF3) and related compounds are introduced as new solvents for traditional organic synthesis and for fluorous synthesis. BTF is more environmentally friendly than many other organic solvents and is available in large quantities. BTF is relatively inert and is suitable for use as a solvent for a wide range of chemistry including ionic, transition-metal catalyzed and thermal reactions. It is especially useful for radical reactions, where it may replace benzene as the current solvent of choice for many common transformations. BTF and related solvents are also crucial components of fluorous synthesis since they can dissolve both standard organic molecules and highly fluorinated molecules. This chapter provides an overview of the reactivity and toxicological properties of BTF and analogs and then summarizes their recent uses as reaction solvents in both traditional organic and new fluorous synthesis.

The Higher Fullerenes: Covalent Chemistry and Chirality

Abstract: Many higher fullerenes, including some of their isomers, can be separated by high performance liquid chromatography (HPLC) on a number of stationary phases, a remarkable fact in view of the similarity of the carbon spheroids which differ mainly in shape and electronic properties of their π-systems, in addition to slight variations in size. Except for C70, which is available in preparative amounts from fullerene soot extract without tedious HPLC purification and has been derivatized in many ways, most separations of the larger carbon spheroids are limited to the milligram scale and require a multistep chromatographic purification. Furthermore, taking into account the relatively small amounts of these carbon cages contained in fullerene soot, the availability of pure higher fullerenes has remained the bottleneck in the field of their multifaceted chemistry. Still, a number of pure adducts of C76, C78 and C84 has now been isolated and characterized, and reactivity as well as regioselectivity principles begin to emerge for the higher fullerenes.

Reactions in Supercritical Carbon Dioxide (scCO2)

Abstract: The present contribution highlights recent developments in the application of compressed (liquid or supercritical) carbon dioxide as a solvent for chemical reactions. After a brief introduction to the basic physical properties of scCO2, some practical aspects of the use of compressed gases are discussed. A survey of successful applications of compressed and particularly supercritical CO2 in organic synthesis is provided with an emphasis on metal-catalyzed reactions.

Phospholipases as Synthetic Catalysts

Abstract: Natural phospholipids can be completely modified with a group of hydrolytic enzymes found in living organisms. Phospholipase A1, phospholipase A2, and 1,3-specific lipases are hydrolases which can selectively cleave the ester bonds at position sn1 and sn2. The compounds of partial hydrolysis can be reacylated chemically. Each of the compounds obtained can then be modified with the very efficient phospholipase D which can effect polar head substitution in the presence of an alcohol as a phosphoryl acceptor. The enzymes from bacterial sources are readily available from culture broth and are highly selective. Phospholipase C can be used to obtain diacylglycerol and organic phosphates as hydrolysis products. The sequential use of the latter enzymes allows the preparation of organic diphosphates. The factors affecting the specificity and selectivity of these enzymes is discussed.

Screening for Novel Enzymes

Abstract: The development of new biocatalysts as synthetic tools for chemists has been expanding rapidly over the last several years. It is now possible either to discover or engineer enzymes with unique substrate specificities and selectivities that are stable and robust for organic synthesis applications. This has been made possible by the application of the newest screening and selection technologies that allow rapid identification of enzyme activities from diverse sources.We focus on how to recognize and tackle important issues during the strategic design and implementation of screening for novel enzymes. We also review the approaches available for biocatalyst discovery and relate them to the isolation of thermostable enantioselective esterases and alcohol dehydrogenases for the purpose of illustration and discussion.

Carbon-Rich Molecular Objects from Multiply Ethynylated π-Complexes

Abstract: The synthesis and properties of a series of multiply ethynylated π-complexes of iron, manganese, and cobalt are described. These complexes were shown to be useful as modules for the construction of larger organometallic carbon-rich molecular objects which can be regarded as segments out of either a planar organometallic all-carbon net or an expanded fullerene, a fullerenyne. Screening of the material properties of these objects showed that some of them form organometallic liquid crystalline phases or stable Langmuir-Blodgett films at the air-water interface. The methodology for the construction of these organometallic modules should lead to the future synthesis of larger segments of organometallic all-carbon nets of different topologies.

Cyclic and linear acetylenic molecular scaffolding

Abstract: During the past decade, the construction and investigation of expanded acetylenic π-chromophores has become a central area of chemical research. It has been fueled by the availability of new synthetic methods, in particular Pd(0)-catalyzed cross-coupling reactions, the discovery of the antitumor activity of a series of natural compounds possessing reactive enediyne π-chromophores, and the need for new nanoscale molecular and polymeric materials that exhibit unusual electronic and optical functions and properties. In this review, synthetic approaches to the cyclo[n]carbons (cyclo-C n ), n-membered monocyclic rings of sp-hybridized C-atoms with unique electronic structures resulting from two perpendicular systems of conjugated π-orbitals — one in-plane and one out-of-plane — are presented. In the following sections, the syntheses and properties of perethynylated molecules, constituting a versatile “molecular construction kit” for acetylenic molecular scaffolding, are discussed. Examples of such compounds are perethynylated annulenes, radialenes, olefins and cumulenes, or transition metal complexes. The article concludes by outlining advances ion novel acetylenic polymers, such as poly(triacetylene), the third linearly conjugated polymer with a non-aromatic, all-carbon backbone.

Asymmetric [4+2] Cycloadditions Mediated by Sulfoxides

Abstract: Asymmetric [4,2] cycloadditions involving the use of enantiomerically pure sulfoxides as the main controller of stereoselectivity are reviewed. Diels-Alder reactions with sulfinyldienes and sulfinyldienophiles, 1,3-dipolar reactions with vinylsulfoxides, and hetero-Diels-Alder reactions are the main objectives of this review. The influence of the sulfinyl group on the reactivity, regioselectivity, and especially stereoselectivity of these reactions has been mainly considered in order to understand the synthetic scope and limitations of the sulfinyl group acting as a chiral inductor in these reactions. Apparent deficiencies in proposed stereochemical models have been also highlighted.

Biocatalytic Approaches for the Synthesis of Enantiopure Epoxides

Abstract: Because of their high chemical versatility, enantiopure epoxides, as well as their corresponding vicinal diols, are recognized as being high value intermediates in fine organic chemistry, in particular for the synthesis of biologically active compounds in optically pure form.Therefore, research work aimed to set up efficient procedures allowing for the preparation of such target molecules has been intensively developed recently, leading to the emergence of various new methods based on either conventional chemistry or on biocatalytic reactions. In this review, we will focus on the use of such enzymatic approaches for the synthesis of enantiopure epoxides. Examination of the recent literature indicates that two general strategies have thus been developed, i.e. (a) the formation of the epoxide ring itself from an appropriate precursor (in general the corresponding olefin) and (b) the resolution of racemic substrates already bearing an oxirane ring. Several of these approaches have been shown to allow the synthesis of epoxides of different structures,which were thus obtained in enantiomerically enriched or even enantiopure form.

Glycosyltransferase-Catalyzed Synthesis of Non-Natural Oligosaccharides

Abstract: Enzymes are indispensable tools in modern organic synthesis. Recent progress in cloning techniques, microbiology and protein purification supply an ever growing number and quantity of preparatively useful biocatalysts. Initially used to synthesize compounds found in nature, enzymes are now probed on non-natural substrates to an increasing degree. They work on highly functional and unprotected substrates under mild and environmentally friendly conditions. In addition, they exhibit an excellent chemo-, regio- and stereoselectivity. The following article will focus on the application of glycosyltransferases in the area of molecular glycobiology. Selected reactions with non-natural substrates will be discussed.

Metal Catalysis in Water

Abstract: Organometallic catalysis in aqueous systems is now a very active field or research, both from an academic and an industrial point of view. The use of transition-metal catalysts in water or in a two-phase system offers the same advantages as in a usual organic medium. However they simplify the separation of the catalyst from the products, eventually for its recycling, and this is very important for large-scale chemical processes. The use of water as the solvent can also exhibit different selectivities to those shown in an organic medium. A comprehensive review concerning organometallic catalysis in aqueous solution is presented here, with particular emphasis on the application in organic synthesis.

Catalytic Antibodies for Organic Synthesis

Abstract: Monoclonal antibodies with strong binding affinities tailored to any molecular target can be produced from immunized mice using hybridoma technology. Due to their directable binding specificities and ease of preparation, monoclonal antibodies are used in the daily practice of biological research as well as in many diagnostic applications. Since 1986 monoclonal antibodies with catalytic properties have been prepared by immunizing mice with stable transition state analogs of chemical reactions, thereby providing a versatile source of novel biocatalysts. This review discusses catalytic antibodies with respect to organic synthetic reactions.

Electron Correlation in Small Molecules: Grafting CI onto CC

Abstract: Among the post-Hartree-Fock methods, those based on the coupled cluster (CC) ansatz for the electronic wave function proved to be extremely valuable in quantum chemical computations of the molecular electronic structure, being capable of attaining chemical accuracy for many molecular properties of interest. While the widely exploited single reference (SR) singles and doubles CC method (CCSD) is remarkably efficient in handling dynamic correlation, a proper account of nondynamic correlation, which becomes essential in the presence of the quasidegeneracy, requires multireference (MR) formalism. In view of the complexity and computational demands of the available MR CC methods, it is highly desirable to design SR CCSD-type approaches that are capable of accommodating both types of correlation effects. One avenue to achieve this goal is offered by the so-called externally corrected (ec) CCSD methods, which exploit some independent source of higher than pair clusters — whose importance rises with the increasing quasidegeneracy — to correct the standard CCSD equations. In view of the complementarity of SR CC and MR configuration interaction (CI) methods in their ability to describe the dynamic and nondynamic correlation effects, a particularly suitable and affordable external source proved to be an MR CISD wave function, based on a small active or model space, leading to the so-called reduced multireference (RMR) CCSD approach. Following a brief outline of the origins and of the status quo of the ecCCSD and RMR CCSD methodologies, their performance is illustrated by a few examples, and their potential and relationship with other approaches is discussed.

Extremal Electron Pairs — Application to Electron Correlation, Especially the R12 Method

Abstract: The concept of extremal electron pairs is discussed in the context of coupled-cluster theory and the MP2-R12 method. Using extremal pairs the numerical stability of R12-methods is considerably improved, which is demonstrated for CCSD(T)-R12 calculations of the molecules F2, N2, and Be2.

Macrocyclic Structurally Homoconjugated Oligoacetylenes: Acetylene- and Diacetylene-Expanded Cycloalkanes and Rotanes

Abstract: There is ample evidence for the significance of modern acetylene chemistry and its role for the future development in several areas of organic chemistry. In this chapter, the successful syntheses and attempted approaches to macrocyclic structurally homoconjugated oligoacetylenes and oligodiacetylenes, as well as some of their physical properties, are discussed. Such compounds, which are formally derived from permethylated cycloalkanes by insertion of -C≡C- or -C≡C-C≡C-fragments between each pair of adjacent sp 3-hybridized carbon atoms, have been termed [n]pericyclines and expanded [n]pericyclines, respectively. These and analogous hydrocarbons formally derived from [n]rotanes (perspirocyclopropanated [n]pericyclines and “exploded” [n]rotanes) as well as heteroanalogues of [n]pericyclines are presented. In addition, the preparations and properties of macrocycles with mixed ethyne and butadiyne expanders as well as the attempted syntheses of perspirocyclopropanated “exploded” [n]rotanes are also covered. In view of the reported properties, the question of cyclic homoconjugation and homoaromaticity in these unconventional compounds is discussed. Finally, some chemical transformations of these macrocyclic oligoacetylenes and oligodiacetylenes, e.g. the conversion of diacetylene-expanded [n]rotanes into crowns of thiophenes, are presented.

Incorporation of Noncoded Amino Acids by In Vitro Protein Biosynthesis

Abstract: The method of site-specific mutagenesis with noncoded amino acids using suppression of a nonsense codon by a semi-synthetic tRNA was first introduced in 1989. Initially used to probe the tolerance of the protein biosynthetic machinery for compounds other than the 20 primary amino acids, the method has since been applied to study a widely diverse range of biological problems. The ability to introduce side chains bearing subtle structural and electronic differences, fluorescent probes, isotope labels, photolabile protecting groups, chemical handles and photoactivated cross-linkers at unique sites has facilitated studies not currently accessible by other means. Improvements and alternatives to the early methodology are considered as well as some interesting recent applications.

Functionalization and Properties of Designed Folded Polypeptides

Abstract: Designed, folded and functionalized polypeptides and proteins constitute an enormous pool of new shapes, new functions and new materials. By taking advantage in the chemical laboratory of the principles of protein folding used by nature, strategies have so far been developed for the engineering of new catalysts, metalloproteins, heme proteins, glycoproteins, receptors and mimics of the components of the immune system. Catalysts have been developed that catalyze reactions not performed by nature and uncommon folded polypeptide motifs have been engineered and structurally characterized. The search for and exploitation of the tremendous number of proteins yet to be discovered has thus begun. Understanding of the protein folding problem has now reached a level where the design of peptides that approach a hundred residues in size is feasible, although not trivial, and clearly sequence dependent. The most frequently designed motif is the four-helix bundle, but recently monomeric triple-stranded β-sheet structures have also been reported as well as a ββα-motif, helical coiled coils and triple helices. Template-assembled polypeptides as well as linear sequences have been shown to fold into designed solution structures and these and other motifs are now key targets for functionalization. This review describes the principles and strategies used in the design of these motifs, as well as their structural characterization. Strategies for functionalization using both the naturally occurring amino acids and post-synthetic incorporation of non-natural functionality will be described, as well as the level of function that has been achieved by rational design.