Diastereocontrol in Radical Addition to ß-Benzyloxy Hydrazones: Revised Approach to Tubuvaline and Synthesis of O-Benzyltubulysin V Benzyl Ester.

Radical addition to chiral N-acylhydrazones has generated unusual amino acids tubuphenylalanine (Tup) and tubuvaline (Tuv) that are structural components of the tubulysin family of picomolar antimitotic agents and previously led to a tubulysin tetrapeptide analog with a C-terminal alcohol. To improve efficiency in this synthetic route to tubulysins, and to address difficulties in oxidation of the C-terminal alcohol, here we present two alternative routes to Tuv that (a) improve step economy, (b) provide modified conditions for Mn-mediated radical addition in the presence of aromatic heterocycles, and (c) expose an example of double diastereocontrol in radical addition to a ß-benzyloxyhydrazone with broader implications for asymmetric amine synthesis via radical addition. An efficient coupling sequence affords 11-O-benzyltubulysin V benzyl ester.

Spatial variability of arsenic in Indo-Gangetic basin of Varanasi and its cancer risk assessment.

The Indo-Gangetic alluvium is prime region for intensive agricultural. In some areas of this region, groundwater is now becoming progressively polluted by contamination with poisonous substances like arsenic. Intensive irrigation with arsenic contaminated ground water in dry spell results in the formation of As(III) which is more toxic. Thus groundwater quality assessment of Gangetic basin has become essential for its safer use. Therefore we under took study on the spatial variability of arsenic by collecting georeferred groundwater samples on grid basis from various water sources like dug well, bore and hand pumps covering the river bank region of Ganga basin. Water quality was investigated through determination pH, EC, TDS, salinity, Na, K, Ca, Mg, SAR, SSP, CO3, HCO3, RSC, Cl, As, Fe, Zn, Mn and Cu, etc. Results pointed severe As contamination in ground water of three sites of the study area. ARC GIS software is now able to process maps along with tabular data and compare them well, to provide the spatial visualization of information and using this tool, the Geographical Information System (GIS) of arsenic was developed. It was noticed from spatial maps that concentration of arsenic was more near the meandering points of Ganga.

Stereoselective access to tubuphenylalanine and tubuvaline: improved Mn-mediated radical additions and assembly of a tubulysin tetrapeptide analog.

Synthesis of tubuphenylalanine and tubuvaline (Tuv), α-substituted γ-amino acid building blocks for tubulysin family of antimitotic compounds, has been improved using a radical addition reaction in the presence of unprotected hydroxyl functionality. The key carbon-carbon bond construction entails stereoselective Mn-mediated photolytic additions of alkyl iodides to the C=N bond of chiral N-acylhydrazones, and generates the chiral amines in high yield with complete stereocontrol. Reductive N-N bond cleavage and alcohol oxidation converted these amino alcohols into the corresponding γ-amino acids. The route to Tuv proceeded via peptide coupling with serine methyl ester, followed by a high-yielding sequence to convert the serine amide to a thiazole. Finally, peptide bond construction established the tubulysin framework in the form of a C-terminal alcohol analog. Attempted oxidation to the C-terminal carboxylate was unsuccessful; control experiments with dipeptide 18 showed a cyclization interfered with the desired oxidation process.

Comparisons between membrane, bridge and cantilever miniaturized resistive vacuum gauges.

Using bulk micromachining, meander-shaped resistor elements consisting of 20 nm Cr and 200 nm Au were fabricated on 1 µm thick silicon nitride membranes, bridges, and cantilevers. The resistance change as a function of pressure depends strongly on the thermal resistance of the two metal lines connecting the heated resistor to the silicon bulk (cold junction) and on the thermal resistance of the silicon nitride. Relative resistance changes ranging from about 3% (small membrane) to 20% (bridge) per mW of input power were obtained when operating the devices in constant voltage mode. The pressure where maximum sensitivity of these gauges occurs depends on the distance 'd' between the periphery of the heated resistor element and the silicon cold junction. Devices with 'd' ranging from 50 µm to 1,200 µm were fabricated. Assuming that pressures can be reliably measured above the 10% and below the 90% points of the resistance versus pressure curve, the range of these devices is about two orders of magnitude. By integrating two devices, one with d = 65 µm and one with d = 1,200 µm on the same chip and connecting them in series, the range can be increased by about a factor of three. By fabricating the cantilever devices so that they curl upon release, it will be shown that these devices also exhibit larger range due to varying 'd'.

Displaced middle-third fractures of the clavicle-operative management.

Displaced midclavicular fractures resulting in malunion with shortening and rotational deformity does not remodel in adults and incidence of non-union in displaced midshaft clavicular fractures is between 10-15% especially in those with an initial shortening of >20 mm.We have treated 10 patients of displaced middle-third clavicle fracture by open reduction and internal fixation with plate and screws and found it to be very effective in respect to rehabilitation, union and cosmesis.

Free standing luminescent silicon quantum dots: evidence of quantum confinement and defect related transitions.

We report the synthesis of luminescent, free standing silicon quantum dots by dry and wet etching of silicon and silicon oxide core/shell nanostructures, which are synthesized by controlled oxidation of mechanically milled silicon. Dry and wet etching performed with CF(4) plasma and aqueous HF, respectively, result in the removal of the thick oxide shell of the core/shell nanostructures and affect an additional step of size reduction. HF etch is capable of producing isolated, spherical quantum dots of silicon with dimensions ∼ 2 nm. However, the etching processes introduce unsaturated bonds at the surface of the nanocrystals which are subsequently passivated by oxygen on exposure to ambient atmosphere. The photoluminescence spectra of the colloidal suspensions of these nanocrystals are characterized by double peaks and excitation dependent shift of emission energy. Comparison of the structural, absorption and luminescence characteristics of the samples provides evidence for two competing transition processes--quantum confinement induced widened band gap related transitions and oxide associated interface state mediated transitions. The results enable us to experimentally distinguish between the contributions of the two different transition mechanisms, which has hitherto been a challenging problem.

Synthesis of gamma-amino esters via Mn-mediated radical addition to chiral gamma-hydrazonoesters.

Highly stereoselective Mn-mediated couplings of alkyl iodides with chiral N-acylhydrazones bearing ester functionality afford a series of gamma-hydrazino esters, including gamma-substituted, alpha,gamma-disubstituted, and alpha,alpha,gamma-trisubstituted examples. In contrast to prior work with chiral N-acylhydrazones, high stereoselectivity was observed even in the absence of Lewis acid. Microwave-assisted acylation with trifluoroacetic anhydride and reductive N-N bond cleavage provided the gamma-amino ester functionality in a synthetically useful N-TFA-protected form.