Stereocontrol in Organic Synthesis Using the Diphenylphosphoryl Group

In 1959, Horner showed that metalated alkyldiphenylphosphane oxides react with aldehydes or ketones to give alkenes. With this reaction, the diphenylphosphoryl (Ph₂PO) group made its entrance into synthetic organic chemistry. In the thirty-six years since that date, extensive research has shown that this olefination, the Horner–Wittig reaction, has unique properties that make it much more than simply the phosphane oxide cousin of the more famous phosphorus-based olefinations—the Wittig reaction (based on phosphonium salts) and the Wadsworth–Emmons reaction (based on phosphonate esters). Early work on the Horner–Wittig reaction concentrated on the reactivity of phosphane oxides and the regioselectivity of their reactions, but more recently the power of the Ph₂PO group to control the stereochemistry of alkenes, and to produce “on demand” either stereoisomer in high stereochemical purity, has emerged. From the study of these stereocontrolled Horner–Wittig reactions arose the realization that the Ph₂PO group is useful not only for the control of the two-dimensional stereochemistry of alkenes, but also of three-dimensional stereochemistry in general. After a brief introduction to phosphane oxide chemistry, this review will examine the Horner–Wittig reaction, in both its original and “stereocontrolled” varieties. From there, we will move on to an account of the stereoselective construction of molecules containing the Ph₂PO group, concentrating on the stereochemical directing effects of the Ph₂PO group and on the role of its unique combination of attributes—steric bulk, electronegativity, and Lewis basicity—in controlling these reactions. Finally, we will present what is intended as a practical guide to this chemistry, covering the type of functionalized alkenes that have been made with the help of the Ph₂PO group and giving guidelines that we hope will help the organic chemist to make the most of the chemistry the Ph₂PO group has to offer.     

Characterization of glucoamylase immobilized on celite

Immobilization of glucoamylase (EC 3.2.1.3) on Celite R649 bio-catalyst carrier for hydrolysis of maltose and maltodextrin has been investigated in both packed bed and recirculated batch reactors. The kinetics parameters on the hydrolysis of maltose were estimated from the packed bed reactor. It is found that this immobilized enzyme is as efficient as the soluble enzyme in catalyzing hydrolysis of maltose. However, it is less efficient than the soluble enzyme in hydrolyzing 30% (w/v) maltodextrin, giving a maximum dextrose equivalent (DE) value of 96.0% instead of 98.2%.     

Efficient total synthesis of pulchellalactam,a CD45 protein tyrosine phosphatase inhibitor

A new approach to a CD45 protein tyrosine phosphatase inhibitor, pulchellalactam, is described. The key step of the sequence involves addition and elimination of an enolic lactam in a single step and 70% yield, employing an organocuprate reagent. The resulting alpha,beta-unsaturated lactam could be condensed with isobutyraldehyde to produce Z-pulchellalactam or converted into siloxypyrrole, which was subjected to the BF(3) x Et(2)O-promoted coupling reaction with isobutyraldehyde to afford E-pulchellalactam after E1-cB elimination and TFA deprotection. This first total synthesis afforded Z-pulchellalactam in six steps and 32% overall yield from Boc-glycine. The same sequence of reactions could also be applied to the liquid- or solid-phase synthesis of trifunctionalized pulchellalactam derivatives.     

A sequential molecular mechanics/quantum mechanics study of the electronic spectra of amides

We report gas-phase electronic spectra of formamide, N-methyformamide, acetamide, and N-methylacetamide at 300 K calculated using a combination of classical molecular dynamics and time-dependent density functional theory (TDDFT). In comparison to excitation energies computed using the global minima structures, the valence npi* and pi(nb)pi* states show a significant red-shift of 0.1-0.35 eV, while smaller shifts are found for the n3s and pi(nb)3s Rydberg states. In this work, we have identified the physical origin of these shifts arising from variations of the molecular structure. We present simple relationships between key geometrical parameters and spectral shifts. Consequently, electronic spectra can be generated directly from ground-state structures, without additional quantum chemical calculations. The electronic spectrum of formamide in aqueous solution is computed using TDDFT using an explicit solvent model. This provides a quantitative determination of the condensed-phase spectrum. In general, this study shows that temperature effects can change the predicted excitation energies significantly and demonstrates how electronic spectra at elevated temperatures can be computed in a computationally efficient way.     

Experimental measurement and prediction of hydrate forming conditions in the nitrogen-propane-water system

Experimental data on initial hydrate formation conditions have been obtained for the nitrogen-propane-water system in the L₁HG, L₁L₂H, and L₁L₂HG regions, where L₁ is the water rich liquid phase, L₂ is the hydrocarbon rich liquid phase, H is the hydrate and the G is the vapor phase. The measurements covered a range of temperatures from about 275 to 293 K and pressures from about 0.3 to 17.0 MPa. The concentrations covered for the L₁HG region extended from 0.94 to 75.0 mole percent propane in the gas phase, and for the L₁L₂H region they extended from 83.1 to 99.0 mole percent in the condensed liquid phase. Four-phase measurements were made at concentrations of propane from 18.1 to 71.1 mole percent in the gas phase.The experimental data were used to find a fitted binary interaction parameter for predicting hydrate formation in systems containing nitrogen and propane.     

Application of the energy gap law to the decay of charge transfer excited states,solvent effects

Values of non-radiative decay rate constants (k_nr) and emission energies (E_cm) have been obtained for Os(Phen₃)²⁺ in a series of solvents and the results are consistent with the energy gap law. For hydroxylic solvents like water or methanol related studies suggest the existence of strong, specific contributions to the vibrational trapping energy of the solvent.     

An Education in Robustness

A case study is presented of the application of robustness analysis to the choice of examination subjects to be made by a 14-year-old girl. The analysis is conducted in terms of the desirable future career options which may be preserved by different combinations of subjects, and also of the balance with topics selected for their intrinsic interest. The approach, which employs very limited technical apparatus, is justified on a number of grounds-in particular, the crucial importance of uncertainty, and the need for understanding and acceptance by a "client" very unlike the corporate manager. Some tentative conclusions are reached on the extension of such methods to other cases of decision-makers with little, if any, resources to control except their own lives.     

Vertically well aligned P-doped ZnO nanowires synthesized on ZnO-Ga/glass templates

Vertically well aligned P-doped ZnO nanowires were prepared on ZnO-Ga/glass templates at 550 degrees C by reactive evaporation without metal catalysts and the nanowires were found to be single crystalline with the würtzite structure, oriented in the c-axis direction; the P-doping shortened the physical lengths of the ZnO nanowires without changing their diameter, and furthermore, the introduction of P atoms resulted in a much weaker and broader ZnO band edge emission.     

A multi-residue cation-exchange clean up procedure for basic drugs in produce of animal origin

There is considerable interest in maximising the amount of information obtained from animal product analyses, when screening for the presence of veterinary drug residues. One of the barriers to effective multi-residue analysis to date has been a lack of effective clean up procedures to isolate a wide range of residues from the potential interferents, which may be present in both simple and complex (including processed) foods. A cation-exchange clean up has, therefore, been developed for use with acetonitrile extracts of foods, when analysing for several basic drug groups (sulfonamides, benzimidazoles, levamisole, nitroimidazoles, tranquillisers and fluroquinolones). The clean up procedure has also been shown to be effective using a modified extraction solvent for malachite green and leucomalachite green in fish.Several of the key parameters that influence analyte recovery have been investigated and in an optimised procedure, tissue/biofluid samples containing sulfonamides, benzimidazoles, levamisole, nitroimidazoles, tranquillisers and fluoroquinolones are first extracted with acetonitrile. The extract is then dried with sodium sulfate and acidified with glacial acetic acid before loading onto a Bond Elut, strong cation-exchange (SCX) solid phase extraction (SPE) cartridge. Extracts from fish containing malachite green and leucomalachite green can be cleaned up using the same SCX SPE procedure following extraction with citrate buffer/acetonitrile. Typical recoveries of drugs from low level fortified tissues using the optimised procedure lie in the range 53-104% with the exception of carazolol from pig kidney (31%), malachite green from trout (42-51%) and ciprofloxacin from chicken muscle (44%) and from egg (21%).     

DNA-PROTEIN CROSSLINKING IN NORMAL HUMAN SKIN FIBROBLASTS EXPOSED TO SOLAR ULTRAVIOLET WAVELENGTHS

Three normal human skin fibroblast cell lines were exposed to the simulated solar UV radiation produced by a fluorescent sunlamp under conditions in which the wavelength components shorter than either 295, 305 or 315 nm were excluded. The level of DNA-protein crosslinks (DPC) was then measured in those cells using the alkaline elution technique either immediately after irradiation or following a 24 h incubation. In each case, cells were exposed to fluences that induce similar levels of DPC. For cells exposed to 10 kJ m(-2) of sunlamp UV > 295 nm, the level of DPC exhibited a 2-5-fold increase following incubation. In contrast, 40-100% of the DPC were removed upon incubation of cells irradiated with either 100 kJ m(-2) of sunlamp UV > 305 nm or 150 kJ m(-2) of sunlamp UV > 315 nm. A major difference between the effects induced by these wavelength regions is that, in addition to DPC, a very high level of pyrimidine dimers is also produced by sunlamp UV > 295 nm, whereas much lower dimer yields result from treatment with either sunlamp UV > 305 nm or sunlamp UV > 315 nm. A potential role for type II DNA topoisomerase in the formation of these DPC resulting from either the change in conformational structure caused by the presence of a high level of dimers or an involvement of this enzyme in dimer excision repair is discussed.