Stereoselective synthesis of the glycosidase inhibitor australine through a one-pot, double-cyclization strategy

[reaction: see text] A stereocontrolled, convergent synthesis of the alkaloid australine, a glycosidase inhibitor of the pyrrolizidine class, is described. The chiral starting materials were ketone 3, derived from L-erythrulose, and alpha-alkoxy aldehyde 4, prepared from L-malic acid. A key step of the synthesis was the highly stereoselective aldol reaction between 4 and a Z boron enolate derived from 3. Another key step was the one-pot construction of the bicyclic pyrrolizidine system by means of a three-step sequence of SN2 displacements induced by benzylamine on a trimesylate precursor.     

Chemoenzymatic approaches toward dechloroansamitocin P-3

[reaction: see text] The enantioselective total synthesis of proansamitocin, a key biosynthetic intermediate of the highly potent antitumor agent ansamitocin P-3, is described which bears a diene-ene RCM as the key macrocyclization step. Feeding of proansamitocin to an AHBA block mutant Actinosynnema pretiosum (HGF073) yielded ansamitocin P-3 as well as dechloroansamitocin P-3, the latter also being formed upon fermentation in the presence of 3-amino-5-methoxybenzoic acid.     

A RISM approach to the liquid structure and solvation properties of ionic liquids

We test for the first time the performance of the reference interaction site model (RISM) to predict the liquid structure and solvation of room-temperature ionic liquids (RTILs) represented with different degrees of accuracy. The model gives satisfactory results, proposing itself as a possible method to explore and to describe at a chemically realistic level the solvation shell in ionic liquids, which is believed to play a fundamental role in the static electronic and vibrational properties of these systems.     

Synthetic strategies to epoxydiynes and a key synthon of the neocarzinostatin chromophore

We present herein our recent efforts towards the synthesis of epoxydiynes which represent an unusual structural feature of the neocarzinostatin chromophore. A number of different routes to these epoxydiynes have been explored with varying success. Ultimately a concise and convergent approach was developed, which involved the addition of an allenyl zinc bromide to propargylic ketones/aldehydes followed by epoxide formation. This new protocol enabled us to synthesise a fully elaborated epoxydiyne which will find application for our studies towards the total synthesis of the NCS chromophore.     

Gold nanoparticle-initiated free radical oxidations and halogen abstractions

We report on the use of EPR spectroscopy and spin trapping technique to detect free radical intermediates formed in the presence of gold nanoparticles. Phosphine- and amine-protected gold nanoparticles were found to initiate air oxidation of organic substrates containing active hydrogen atoms, such as amines and phosphine oxides. Nanoparticles protected by stronger bound ligands (e.g., thiols) were inactive in these reactions. We also found that gold nanoparticles are able to abstract a halogen atom from the halogenated compounds, presumably due to the high affinity of gold metal for halogens. Reaction of Au nanoparticles with chloroform showed an unusual inverse isotope effect. The trichloromethyl spin adduct was observed when Au nanoparticles were mixed with CDCl(3) but not with CHCl(3). This unexpected behaviour suggests that C-H bond breaking is not the rate-determining step in Au-initiated hydrogen abstraction.     

Hydrogen bonding affects the persistency of alkyl peroxy radicals

The effect of 1,1,1,3,3,3-hexafluoro-2-phenylpropan-2-ol (HFPP) on the persistency of sec-alkyl peroxy radicals has been investigated. The formation of a hydrogen-bonding complex between HFPP and the radical resulted in a large increase in the lifetime of the radical. This variation was accompanied by a decrease in the g-value. An enthalpy change of -3.4 kcal mol-1 was estimated for the formation of the hydrogen-bonded complex.     

Dielectrophoresis for the manipulation of nanobioparticles

Dielectrophoresis (DEP) is a nondestructive electrokinetic mechanism with great potential for the manipulation of bioparticles. DEP is the movement of particles induced by polarization effects in nonuniform electric fields. Since the 1960s, this technique has been successfully used for the manipulation of microbioparticles, such as microorganisms. Moreover, due to the advances in microfabrication techniques, that allowed progressively smaller microstructures to be constructed, DEP can now be used for the manipulation of nanobioparticles. The first research studies on the DEP of nanobioparticles started in the 1990s. Since then, many research groups have carried out outstanding work with DEP of nanobioparticles such as macromolecules, virus, and spores. However, the need of a critical report that integrates these findings is evident. The aim of the present review is to depict the state-of-the-art on the use of DEP for the separation of nanobioparticles and the potential trends of novel applications of this technique. This review compiles and analyzes the significant findings obtained by many researchers. This publication is intended to provide the reader with state-of-the-art information on many research studies focused on DEP to handle nanobioparticles.     

Full-fledged proteomic analysis of bioactive wheat amylase inhibitors by a 3-D analytical technique: Identification of new heterodimeric aggregation states

Wheat proteinaceous alpha-amylase inhibitors (alpha-AIs) are increasingly investigated for their agronomical role as natural defence molecules of plants against the attack of insects and pests, but also for their effects on human health. The wheat genomes code for several bioactive alpha-AIs that share sequence homology, but differ in their specificity against alpha-amylases from different species and for their aggregation states. Wheat alpha-AIs are traditionally classified as belonging to the three classes of tetrameric, homodimeric and monomeric forms, each class being constituted by a number of polypeptides that display different electrophoretic mobilities. Here we describe a proteomic approach for the identification of bioactive alpha-AIs from wheat and, in particular, a 3-D technique that allows to best identify and characterize the dimeric fraction. The technique takes advantage of the thermal resistance of alpha-AIs (resistant to T > 70 degrees C) and consists in the separation of protein mixtures by 2-D polyacrylamide/starch electrophoresis under nondissociating PAGE (ND-PAGE, first dimension) and dissociating (urea-PAGE or U-PAGE second dimension) conditions, followed by in-gel spontaneous reaggregation of protein complexes and identification of the alpha-amylase inhibitory activity (antizymogram, third dimension) using enzymes from human salivary glands and from the larvae of Tenebrio molitor coleopter (yellow mealworm). Dimeric alpha-AIs from Triticum aestivum (bread wheat) were observed to exist as heterodimers. The formation of heterodimeric complexes was also confirmed by in vitro reaggregation assays carried out on RP-HPLC purified wheat dimeric alpha-AIs, and their bioactivity assayed by antizymogram analysis. The present 3-D analytical technique can be exploited for fast, full-fledged identification and characterization of wheat alpha-AIs.