Synthesis of (S)-isoprenoid thiodiphosphates as substrates and inhibitors

Thiolo thiophosphate analogues of isopentenyl diphosphate (IPP), dimethylallyl diphosphate (DMAPP), geranyl diphosphate (GPP), farnesyl diphosphate (FPP), and geranylgeranyl diphosphate (GGPP) were synthesized. Inorganic thiopyrophosphate (SPP(i)) was prepared from trimethyl phosphate in four steps. The tris(tetra-n-butylammonium) salt was then used to convert isopentenyl tosylate to (S)-isopentenyl thiodiphosphate (ISPP). (S)-Dimethylallyl (DMASPP), (S)-geranyl (GSPP), (S)-farnesyl (FSPP), and (S)-geranylgeranyl thiodiphosphate (GGSPP) were prepared from the corresponding bromides in a similar manner. ISPP and GSPP were substrates for avian farnesyl diphosphate synthase (FPPase). Incubation of the enzyme with ISPP and GPP gave FSPP, whereas incubation with IPP and GSPP gave FPP. GSPP was a substantially less reactive than GPP in the chain elongation reaction and was an excellent competitive inhibitor, K(I)(GSPP) = 24.8 microM, of the enzyme. Thus, when ISPP and DMAPP were incubated with FPPase, GSPP accumulated and was only slowly converted to FSPP.     

Markhasphingolipid A,new phytosphingolipid from the leaves of Markhamia stipulata var. canaense V.S. Dang

Abstract

From the leaves of Markhamia stipulata var. canaense V.S. Dang, one new phytosphingolipid, named markhasphingolipid A (6) together with five known compounds, 4’,7-O-dimethylapigenin (1), narigenin (2), tectoquinone (3), mollic acid (4), 1-hexadecanoyl-sn-glycerol (5) were classified by various chromatographic methods. Their structures were designated by IR, UV, HR-ESI-MS, HR-ESI-MS/MS and NMR experiments. All compounds were recognized for the first time from this species. The cytotoxicity of all n-hexane fractions and isolated compounds (5 & 6) against three human cancer cell lines (HeLa, HepG2, and MCF-7) were evaluated by SRB assay. All n-hexane fractions expressed cytotoxic effect on three tested cancer cell lines (at the concentration of 100?μg/mL, percent of cytotoxicity ranged from 55.81% to 95.83%) as well as compound 5 (IC₅₀ ranged from 48.51 to 63.30?μM) whereas fraction H.I and compound 6 did not show activity.

     

Polymer-supported palladium catalysed Suzuki-Miyaura reactions in batch and a mini-continuous flow reactor system

A polymer-supported palladium(II) salen-type complex exhibited catalytic activity in the cross-coupling reaction of various aryl bromides and heteroaryl bromides with phenylboronic acid in a mini-continuous flow reactor system at elevated temperatures in a phosphine-free system. The reaction was also performed in batch using a number of different solvent systems in order to optimise conditions. The catalytic mini-reactor can be used repeatedly over several cycles in the Suzuki-Miyaura cross-coupling reaction. While the diameter of the flow channel is 3 mm, the macroporous resin supported catalyst is solvent expanded to completely fill the channel. Consequently, the liquid path is through the micro channels of the macroporous resin structure. Intensification of the process over the stirred batch reaction is through increased reagent-catalyst contact and results in a 20-fold increase in the rate of reaction. The residence/space time on the reactor is 10.5 min, compared to 24 h in batch, which means that a diversity of starting materials can be screened over a short period of time. To demonstrate the utility of the system, a diversity of aryl and heteroaryl bromides have been studied.     

Recognition of multiple substrate motifs by the c-ABL protein tyrosine kinase

Using a combinatorial peptide library that is based on the one-bead one-peptide approach we identified 14 peptide substrates for the c-ABL protein tyrosine kinase, which define three distinct consensus sequence groups. This is distinct from many serine/threonine kinases, which often phosphorylate only one major consensus sequence. The three consensus sequences accurately predict phosphorylation sites in cellular ABL substrates proven to play a role in cell signaling. Our data suggest that protein tyrosine kinases have evolved to recognize multiple substrate motifs.     

Synthesis and Characterization of Silica Gels Functionalized with Monochlorotriazinyl β-Cyclodextrin and their Sorption Capacities towards Organic Compounds

Different supports, containing a new derivative of-cyclodextrin – monochlorotriazinyl-cyclodextrin (-CDMCT) – used forthe reduction of pollutants in waste water, have beenprepared. They are based on silica gel, initially eithercoated with polyethyleneimine (PEI) or grafted with3-aminopropyltrimethoxysilane, functionalized in asecond step with -CDMCT. In order to obtainsorbents with high -cyclodextrin content andmaximum accessibility of the -CD cavity, thefuntionalization was studied while varying experimentalconditions. Thermogravimetry, Raman spectroscopy,specific surface area and pore size distribution were usedfor the characterization of supports. Sorption experimentsshow that these sorbents have sorption capacities towardssome organic pollutants. The mechanism of sorption is bothphysical adsorption in the polymer network (for supportsobtained by coating) and/or the formation of an inclusioncomplex between -CDMCT and guest molecules.     

Twistfree and Papapetrou vacuum spacetimes with a spacelike killing vector

We show that, for the case of vacuum solutions of the Einstein equations with a spacelike hypersurface orthogonal Killing vector /³ and associated metricds ² =e ^2U (dx ³)² +e ^–2U _ab dx ^a dx ^b whereU is not a constant, there exists at every point of the quotient 3-space a plane of vectorsK ^a such that £_KR_ab=0 andK ^a R_ab=0 whereR{inab} is the Ricci tensor formed from _ab . Then in the case whereU{in,a} is a timelike or spacelike vector in the quotient 3-space, Petrov type I solutions of the vacuum field equations are obtained. In the simpler case whereU{in,a} is a null vector in the quotient 3-space, the complete solution of the vacuum field equations is obtained. It is shown that this solution is Petrov type III of Kundt's class. For the case of Papapetrou solutions where there is a twist potential which is a function ofU, solutions corresponding to the twistfree solutions are given.     

Silver-catalyzed ring-opening of cyclopropenes: preparation of tertiary α-branched allylic amines

Herein we report a silver-catalyzed ring-opening of cyclopropenes by addition of amines. This transformation is thought to occur via an argentocarbenium intermediate and affords tertiary α-branched allylic amines in good yields and high regioselectivity. The protocol applies to various primary and secondary amines, as well as sterically hindered cyclopropenes. Friedel–Crafts cyclization of the cationic intermediate occurs as a competitive pathway to form methyl-indene.     

Study of the isomeric ratios in photonuclear reactions of natural holmium and lutetium induced by bremsstrahlungs with endpoint energies in the giant dipole resonance region

We have determined the isomeric ratios in ¹⁶⁵Ho(γ, n)^164m,gHo and ¹⁷⁵Lu(γ, n)^174m,gLu photonuclear reactions of natural holmium and lutetium induced by bremsstrahlungs with end-point energies in the giant dipole resonance (GDR) region. The investigated samples were irradiated at electron accelerator Microtron MT-25 of the Flerov Laboratory of Nuclear Reaction, Joint Institute for Nuclear Research, Dubna, Russia. The gamma spectra of the samples irradiated were measured with spectroscopic system consisting of 8192 channel analyzer and high-energy resolution (180 keV at gamma ray 1332 keV of ⁶⁰Co) HP(Ge) semiconductor detector Canberra. The GENIE2000 (Canberra) computer program was used for data processing. The results were discussed and compared with those of other authors.     

A sequential fluid–solid weak coupling analysis of the SPE in stressed Si layers

The kinetically driven growth instability in stressed solids has been a subject of recent investigation as there is an increasing interest in the effects of non-hydrostatic stresses on crystal growth processes. Recent experimental and modeling work have shown that the effect of stress on the solid phase epitaxy (SPE) growth of crystalline silicon from the amorphous phase is responsible for the roughening of its amorphous–crystalline interface. Although our previous model (Phan, A.-V., Kaplan, T., Gray, L.J., Adalsteinsson, D., Sethian, J.A., Barvosa-Carter, W., Aziz, M.J., 2001. Modelling a growth instability in a stressed solid. Modelling and Simulation in Materials Science and Engineering 9, 309–325.) has been able to explain the observed interfacial instability during the crystal growth of intrinsic silicon, it has not been very successful when extended to the SPE growth process of doped silicon. In an effort to identify the sources that may improve the accuracy and robustness of the previously proposed model, we present in this paper a new approach for modeling the crystal growth in stressed Si layers. The technique is based upon the coupling of finite element analysis, the sequentially weak coupling analysis for fluid–solid interaction, and the marker particle method.