Stereoselective synthesis of 4-hydroxy-2,3,6-trisubstituted tetrahydropyrans

[reaction: see text] Reaction of homoallylic alcohols with aldehydes in the presence of TFA gives, after hydrolysis of the ester, 4-hydroxy-2,3,6-trisubstituted tetrahydropyrans with the creation of three new stereocenters in a single-pot process. By varying the aldehyde component, a variety of functionalized side chains are installed at C-2. The utility of this approach is extended to the enantioselective synthesis of tetrahydropyrans with >99% ee.     

Total synthesis of the thiopeptide antibiotic amythiamicin D

The thiopeptide (or thiostrepton) antibiotics are a class of sulfur containing highly modified cyclic peptides with interesting biological properties, including reported activity against MRSA and malaria. Described herein is the total synthesis of the thiopeptide natural product amythiamicin D, which utilizes a biosynthesis-inspired hetero-Diels-Alder route to the pyridine core of the antibiotic as a key step. Preliminary studies using a range of serine-derived 1-ethoxy-2-azadienes established that hetero-Diels-Alder reaction with N-acetylenamines proceeded efficiently under microwave irradiation to give 2,3,6-trisubstituted pyridines. The thiazole building blocks of the antibiotic were obtained by either classical Hantzsch reactions or by dirhodium(II)-catalyzed chemoselective carbene N-H insertion followed by thionation, and were combined to give the bis-thiazole that forms the left-hand fragment of the antibiotic. The key Diels-Alder reaction of a tris-thiazolyl azadiene with benzyl 2-(1-acetylaminoethenyl)thiazole-4-carboxylate gave the core tetrathiazolyl pyridine, which was elaborated into the natural product by successive incorporation of glycine and bis-thiazole fragments followed by macrocyclization.     

New insights into the coordination chemistry and molecular structure of copper(II) histidine complexes in aqueous solutions

Aqueous solutions of Cu2+/histidine (his) (1:2) have been analyzed in parallel with infrared, Raman, ultraviolet/visible/near-infrared, electron spin resonance, and X-ray absorption spectroscopy in the pH range from 0 to 10. Comprehensive interpretation of the data has been used to extract complementary structural information in order to determine the relative abundance of the different complexes. The formation of six different, partly coexisting species is proposed. Structural proposals from literature have been unambiguously confirmed, refined, or, in several cases, corrected. At highly acidic conditions, Cu2+ and his are present as free ions, but around pH = 2, coordination starts via the deprotonated carboxylic acid group. This results in the intermediate species Cu2+[H3his+(Oc)] and Cu2+[H3his+(Oc)]2. The coordination via Oc is attended with a drop in the pKa value of the other receptor groups resulting in a concomitant conversion to the bidentates Cu2+[H2his0(Oc,Nam)] and Cu2+[H2his0(Oc,Nam)]2, with the latter being dominant at pH = 3.5. Coordination of the imidazole ring begins around pH = 3 and leads to the formation of the mixed ligand complexes Cu2+[H2his0(Oc,Nam)][Hhis-(Oc,Nam,Nim)] and Cu2+[Hhis-(Nam,Nim)][Hhis-(Oc,Nam,Nim)] around pH = 5. It is demonstrated that coordination of the imidazole ring occurs predominantly via the N(pi) atom. At pH > 7, the double-tridentate ligand complex Cu2+[Hhis-(Oc,Nam,Nim)]2 is the major species with the N atoms in the equatorial plane and the O atoms in the axial position. This complex decomposes at pH > 10 into a copper oxide/hydroxide precipitate. The overall results provide a consistent picture of the mechanism that drives the coordination and complex formation of the Cu2+/his system.     

Total syntheses of the bromotyrosine-derived natural products ianthelline, 5-bromoverongamine and JBIR-44

The total syntheses of the bromotyrosine-derived natural products ianthelline, 5-bromoverongamine and JBIR-44 are described and their cytotoxic activity in a cervical cancer (HeLa) cell line and human umbilical vein endothelial cells (HUVECs) are reported.     

Polysubstituted piperidines via iodolactonization: application to the asymmetric synthesis of (+)-pseudodistomin D

Conjugate addition of lithium (S)-N-allyl-N-(α-methyl-p-methoxybenzyl)amide to methyl (E,E)-hepta-2,5-dienoate furnished the corresponding β-amino ester. N-Protecting group manipulation, ring-closing metathesis, and ester hydrolysis gave enantiopure [N(1')-tert-butoxycarbonyl-1,2,3,6-tetrahydropyridin-2'-yl]ethanoic acid. Subsequent iodolactonization gave a bicyclic iodolactone scaffold. This key intermediate was elaborated to (+)-pseudodistomin D [in >99% ee and 7% yield over 16 steps from methyl (E,E)-hepta-2,5-dienoate].     

3-benzoyl-2-quinolinecarboxaldehyde: A novel fluorogenic reagent for the high-sensitivity chromatographic analysis of primary amines

3-Benzoyl-2-quinolinecarboxaldehyde has been synthesized and characterized for use as a precolumn fluorogenic reagent for the ultrahigh sensitivity determination of primary amines by micro-column liquid chromatography with laser-induced fluorescence detection. The reaction conditions and the spectral properties of the derivatives were investigated with standard amino-acids. The detection limits, with an HeCd laser operated at 442 nm, are in the low femtogram range. The linear dynamic range is at least three orders of magnitude. The separation of a standard amino-acid mixture and the high-sensitivity analysis of a hydrolysed protein sample are demonstrated.     

Ceramic Micro-Particles Synthesised using Emulsion and Sol–Gel Technology: An Investigation into the Controlled Release of Encapsulants and the Tailoring of Micro-Particle Size

Controlled release technologies have many applications in such diverse fields as the pharmaceutical, agricultural, cosmetic and food industries, where tailored release rates and protection of the active molecule for delivery at a specific site or time are advantageous. Silica microspheres, with controlled diameters of 10–50 m and containing Orange II dye as a model encapsulant, have been synthesised by combining water-in-oil (w/o) emulsion technology with sol–gel chemistry. The average particle size may be controlled by the microemulsion parameters, including the surfactant and solvent concentrations, and by the sol–gel processing parameters, particularly water-to-silicon alkoxide ratio, pH, temperature, ageing and mixing conditions. Physical properties of the SiO₂ microspheres, which modulate the release rates of the encapsulated molecule (including pore size and tortuosity), are also controlled by the sol–gel process parameters.The effect of synthesis parameters, including surfactant concentration, sol–gel solution pH and drying temperature, on the morphology of the SiO₂ microspheres produced will be discussed. The effect of such parameters on the corresponding release rates of the model encapsulants will also be presented.     

Detection of s-triazine pesticides in natural waters by modified large-volume direct injection HPLC

There is a need for simple and inexpensive methods to quantify potentially harmful persistent pesticides often found in our water-ways and water distribution systems. This paper presents a simple, relatively inexpensive method for the detection of a group of commonly used pesticides (atrazine, simazine and hexazinone) in natural waters using large-volume direct injection high performance liquid chromatography (HPLC) utilizing a monolithic column and a single wavelength ultraviolet-visible light (UV-vis) detector. The best results for this system were obtained with a mobile phase made up of acetonitrile and water in a 30:70 ratio, a flow rate of 2.0 mL min⁻¹, and a detector wavelength of 230 nm. Using this method, we achieved retention times of less than three minutes, and detection limits of 5.7 μg L⁻¹ for atrazine, 4.7 μg L⁻¹ for simazine and 4.0 μg L⁻¹ for hexazinone. The performance of this method was validated with an inter-laboratory trial against a National Association of Testing Authorities (NATA) accredited liquid chromatography-mass spectrometry/mass spectrometry (LC-MS/MS) method commonly used in commercial laboratories.     

Luminescence Characterization of a Novel, Hydrophobically Modified and Heavy Atom-Functionalized, Water-Soluble Polymer

A hydrophobically modified water-soluble polymer, based upon acrylic acid and styryl derivatives, was synthesized. A proportion (ca. 75 mol%) of the styryl residues in the copolymer contain a bromine substituent as a heavy-atom functionality. It has been shown that room-temperature phosphorescence (RTP) can be induced in an acenaphthylene (ACE) label, covalently bound to the polymer chain, through intramacromolecular interactions in dilute solutions of the copolymer. This is the first instance in which RTP has been generated in either label or solubilized guest, in such a fashion. The conformational behavior of the functionalized copolymer, BrSTY/STY/AA, has been studied using RTP, fluorescence lifetime, and time-resolved anisotropy measurements and compared to that of both its unbrominated, styrene-modified analogue, STY/AA, and poly(acrylic acid) PAA itself. The conformation transition which accompanies conversion of each polyacid into the corresponding fully neutralized polysalt is much more dramatic in either hydrophobically modified species than in poly(acrylic acid). Intramacromolecular aggregation leading to the creation of hydrophobic domains within the coils of the macromolecules is enhanced at a low pH and severely impedes segmental motion in the two styrene-modified polyacids. The effect is greater in the bromine-containing polymer, which suggests that more densely packed domains are formed in this species than in STY/AA. In addition to altering the magnitude of the effect that neutralization has upon the molecular dynamics of the polyacid in aqueous media, hydrophobic modification raises the pH range over which the change in conformational behavior of the macromolecule is apparent.