Search

An immense number of chemical reactions are carried out simultaneously in living cells. NatureIs optimization approach encompasses the assembly of reactions in cascades and to embed them in finely tuned metabolic networks. With the vast progress in the field of biocatalysis, man-made cascades, especially redox cascades, have reached a degree of complexity that needs tools for improved control and optimization. Combined strategies from biocatalysis, metabolic engineering and synthetic biology lead to the establishment of artificial metabolic pathways with minimized interference with the cellular host environment. This review will focus on genetic and metabolic engineering tools for the assembly and introduction of de novo redox pathways into the host Escherichia coli and will present state of the art redox cascades performed by tailor-made microbial cell factories.

This review summarizes the current status of knowledge on asymmetric iridium-catalyzed direct hydrogenations of acyclic and cyclic imines. An overview of the most interesting catalysts with respect to selectivity, activity and substrate scope is given, including a discussion of the effects of different reaction conditions on the enantioselectivity of imine reduction. A detailed analysis of proposed imine hydrogenation mechanisms is presented, revealing that a significant number of recent proposals suggest outer sphere mechanisms, implying that the substrate does not bind to the metal centre during the hydrogenation reaction. An intriguing question is how a high enantioselectivity can be achieved in such systems. Generally, the factors governing the stereocontrol of iridium-catalyzed direct imine hydrogenation are little studied. The mechanistic proposals that have been put forward to explain the enantiodiscrimination of selected complexes are reviewed here, showing that the stereocontrol appears to be governed by weak non-bonding interactions between the substrate and the chiral catalyst complex. These selectivity-determining interactions might be modified through coordination of solvent, additive, or product molecules to the iridium complex, providing a rationale for the effect of solvent or additives on the enantioselectivity.

4-Vinyl-substituted 1,3-dioxolan-2-ones are found to be good substrates for Ru-catalyzed allylic alkylations of chelated amino acid ester enolates. cis-1,3-Dioxolan-2-ones are more reactive than the corresponding trans-isomers. The attack occurs preferentially with regioretention at the position of the leaving group with perfect chirality transfer. Therefore, this protocol is a good complement to the Pd-catalyzed processes, which give only linear products with this type of substrate.

The reaction of Zn-chelated glycine enolate with secondary allylic carboxylates bearing a terminal double bond leads to desired branched amino acid esters (III), (V)/(VI), and (VIII) in good to high yields.

Cyclotrimerizations of ethynyl N-methyliminodiacetic acid (MIDA) boronate (1) with 1,6-diynes 2 have been studied, using three different catalysts (based on ruthenium, rhodium, and iridium) and variable reaction conditions. Successful cyclotrimerization reactions were obtained with both Cp*RuCl(cod) and Rh(cod)2BF4/BINAP as pre-catalysts in THF or acetone. Ruthenium-catalyzed cyclotrimerization of an unsymmetrically bromo-substituted diyne (2f) with 1 was successfully scaled up (2 g) and included in a total synthesis strategy toward potential selective inhibitors of tyrosine kinase 2.

The new title Negishi-type cross-coupling reaction expands the scope of monobromophosphines, which are considered as poor substrates so far.

The process is examined in the presence of Rh- and Ru-catalysts concerning the formation of benzopyran and benzofuran derivatives.

Sialyl Lewis x and derivatives have been synthesized using β-1,4-galactosyltransferase and recombinant α-2,3-sialyltransferase and α-1,3-fucosyltransferase. The enzymatic glycosylations have been achieved on preparative scales with in situ regeneration of UDP-galactose, CMP-N-acetylneuraminic acid, and GDP-fucose. Additionally, galactosyltransferase and fucosyltransferases have been studied with respect to their substrate specificity and inhibition

Electronic properties located on the atoms of a molecule such as partial atomic charges as well as electronegativity and polarizability values are encoded by an autocorrelation vector accounting for the constitution of a molecule. This encoding procedure is able to distinguish between compounds being dopamine agonists and those being benzodiazepine receptor agonists even after projection into a two-dimensional self-organizing network. The two types of compounds can still be distinguished if they are buried in a dataset of 8323 compounds of a chemical supplier catalog comprising a wide structural variety. The maps obtained by this sequence of events, calculation of empirical physicochemical effects, encoding in a topological autocorrelation vector, and projection by a self-organizing neural network, can thus be used for searching for structural similarity, and, in particular, for finding new lead structures with biological activity.

A mixture of solids As and Bs in equilibrium with the dissolved compounds A1 and B1 is transformed completely into one pure solid, say Bs, if the dissolved compounds A1⇌B1 are equilibrating in solution. This is applied to transform 1∶1 mixtures of solid diastereomeric amygdalates (2-hydroxy-2-phenylacetates; mandelates) (R,R)-3 + (S,R)-3 prepared from racemic α-amino nitriles (R,S)-1 with (R)-mandelic acid 2 into stereochemically pure single diastereomers (R,R)-3, or (S,R)-3 (de > 97%) (‘asymmetric transformation of the second kind by application of Dimroth’s principle’). Decomposition of the amygdalates (R,R)-3, or (S,R)-3, with aqueous base affords the enantiomerically pure α-amino nitriles (R)-1, or (S)-1 (ten examples). The chiral auxiliary (R)-mandelic acid is recovered almost quantitatively. The optically active α-amino nitriles are hydrolyzed to amides 6, and further to α-N-alkylamino acids 7. N-Benzylamino acids 7 are hydrogenated to α-amino acids 8. Some of the optically active α-amino nitriles 1 are reduced to optically active 1,2-diamines 9. In most cases, absolute configurations could be assigned by comparison of the specific rotations observed with those of authentic compounds.

Enantioselective Diels–Alder reactions of 1,3-cyclohexadiene with N-sulfinylbenzyl carbamate (1a) or N-sulfinyl-p-toluenesulfonamide (1b) promoted by chiral Ti(IV)-based Lewis acids are reported. The endo-adducts were obtained in 15–76% ee.

Reactions of di(alkyn-1-yl)(chloro)silanes, HSi(Cl)(C≡C-R)2, RSi(Cl)(C≡C-R)2 or HSi(Cl)(C≡C-R)C≡C-R′, with an excess of triethylborane, BEt3, proceed slowly (several days) at 100 – 120 ◦C. Twofold 1,1-organoboration of HSi(Cl)(C≡C-R)2 or HSi(Cl)(C≡C-R)C≡C-R′ leads to siloles, independent of R = nBu, tBu, SiMe3. This provides the most straightforward way to siloles bearing both a hydrogen and a chlorine at the silicon atom. However, in the cases of R = Ph, BEt3 acts as 1,2-hydroborating reagent in the intermolecular first step of the reaction, leading to 1-silacyclobutene derivatives. All siloles and 1-silacyclobutene derivatives were characterized by multinuclear NMR spectroscopy (1H, 11B, 13C and 29Si). Comparable 1-silacyclobutene derivatives were formed using 9-borabicyclo[3.3.1]nonane, 9-BBN, as a well established 1,2hydroborating reagent.

Aromatic polyhedral boranes and carboranes lend themselves to the construction of nanoesque structures suited for unique applications. These include cyclic, water-soluble hosts having a lipophilic core; self-assembling nanorods and bilayer membranes using amphiphilic carborane derivatives; and the huge family of functional structures obtainable from the [closo-B 1 2 (OH) 1 2 ] 2 - by derivatization of the hydroxyl groups. The latter species are potentially useful for molecular delivery devices important to biomedicine and material science. New developments in each of these areas of interest will be presented.

The dicesium salt of the icosahedral borane anion dodecahydroxy-closo-dodecaborate(2−), closo-Cs2B12(OH)12, Cs24, was prepared using an improved synthetic pathway. Heating cesium dodecahydro-closo-dodecaborate, closo-Cs2B12H12, Cs21, with 30% hydrogen peroxide added in successive increments at 105−110 °C provided Cs24 in 95% yield. Reaction progress was monitored using 1H-decoupled 11B NMR while 17O NMR provides the most reliable way to detect the presence of peroxides in the reaction solution. The reaction may be safely increased in scale to afford Cs24 in multigram quantities.

A variety of 2-(1-bromoalkyl) benzoic acids 4 undergo intramolecular nucleophilic substitution reaction when treated with a CsF-Celite as solid base in acetonitrile under reflux condition to give the corresponding cyclized phthalides in moderate to very good yield. These 2-(1-bromoalkyl) benzoic acids 4 are formed by the α-bromination of 2-alkylbenzoic acids 3 using N-bromosuccinimide and a catalytic amount of α,α′-azoisobutyronitrile in carbon tetrachloride under reflux.