Efficient and regioselective synthesis of -diiodinated homobenzylic alcohol derivatives: evaluation as potential anticancer IDO/TDO inhibitors.

A simple and direct synthesis of 2,6-diiodophenylethanol building blocks through highly regioselective metalation ()/oxirane S2-type ring opening of 1,2,3-triiodobenzene is described. A significant impact of the nature of the group on the reactivity of the reaction was discovered but not in terms of site-selectivity. The MIE quenching step is easily controlled by the use of slow-reacting electrophiles "oxiranes" providing solely the -diiodinated homobenzylic alcohol derivatives (internal products) in excellent site-selectivity and with stereoretention.

A strained ring for stereoselective synthesis.

The spring-loaded tension of a cyclic allene expedites synthesis of a natural product.

Domino C-C/C-O bond formation: palladium-catalyzed regioselective synthesis of 7-iodobenzo[]furans using 1,2,3-triiodobenzenes and benzylketones.

A facile and efficient synthesis of 7-iodobenzo[]furan derivatives a highly regioselective tandem α-arylation/intramolecular -arylation of 5-substituted-1,2,3-triiodobenzenes and benzylketones is described. Remarkably, the α-arylation coupling reactions initiate exclusively at the least sterically-hindered position of the triiodoarene, which results in a highly chemoselective transformation. The highest yields were observed in reactions between electron-poor 1,2,3-triiodoarenes and electron-rich benzylketones, yet the optimized reaction conditions were found to be tolerant to a wide range of different functional groups.

The CD33 short isoform is a gain-of-function variant that enhances Aβ phagocytosis in microglia.

Background: CD33 is genetically linked to Alzheimer's disease (AD) susceptibility through differential expression of isoforms in microglia. The role of the human CD33 short isoform (hCD33m), preferentially encoded by an AD-protective CD33 allele (rs12459419T), is unknown. Here, we test whether hCD33m represents a loss-of-function or gain-of-function variant.

Generation and trapping of electron-deficient 1,2-cyclohexadienes. Unexpected hetero-Diels-Alder reactivity.

Keto-substituted 1,2-cyclohexadienes were generated by base-mediated (KOt-Bu) elimination, and found to dimerize via an unprecedented formal hetero-Diels-Alder process, followed by hydration. These highly reactive cyclic allene intermediates were also trapped in Diels-Alder reactions by furan, 2,5-dimethylfuran, or diphenylisobenzofuran to afford cycloadducts with high regio- and diastereoselectivity, and could also be intercepted in a hetero-Diels-Alder process with enamine dienophiles. Endo/exo stereochemistry was unambiguously determined via X-ray crystallography in the case of nitrile-substituted 1,2-cyclohexadiene.

Chlorovirus PBCV-1 protein A064R has three of the transferase activities necessary to synthesize its capsid protein N-linked glycans.

chlorella virus-1 (PBCV-1) is a large double-stranded DNA (dsDNA) virus that infects the unicellular green alga NC64A. Unlike many other viruses, PBCV-1 encodes most, if not all, of the enzymes involved in the synthesis of the glycans attached to its major capsid protein. Importantly, these glycans differ from those reported from the three domains of life in terms of structure and asparagine location in the sequon of the protein.

Side-on Coordination in Isostructural Nitrous Oxide and Carbon Dioxide Complexes of Nickel.

A nickel complex incorporating an N O ligand with a rare η -N,N'-coordination mode was isolated and characterized by X-ray crystallography, as well as by IR and solid-state NMR spectroscopy augmented by N-labeling experiments. The isoelectronic nickel CO complex reported for comparison features a very similar solid-state structure. Computational studies revealed that η -N O binds to nickel slightly stronger than η -CO in this case, and comparably to or slightly stronger than η -CO to transition metals in general.

A Mild Method for the Generation and Interception of 1,2-Cycloheptadienes with 1,3-Dipoles.

1,2-Cycloheptadiene is a strained, transient species that has been underutilized as a synthetic building block. Seven-membered cyclic allenes are mostly known for their propensity to undergo rapid dimerization, and relatively little has been reported regarding their cycloaddition reactivity with 1,3-dienes or 1,3-dipoles. This work describes the trapping of 1-acetoxy-1,2-cycloheptadiene and its unsubstituted counterpart, generated via desilylative elimination, with a range of 1,3-dipolar trapping partners, affording complex polycyclic products with high regio- and diastereoselectivity.

Lead-207 NMR spectroscopy at 1.4 T: Application of benchtop instrumentation to a challenging I = ½ nucleus.

The practicality of obtaining liquid- and solid-state Pb nuclear magnetic resonance (NMR) spectra with a low permanent-field magnet is investigated. Obtaining Pb NMR spectra of salts in solution is shown to be viable for samples as dilute as 0.05 M.

Palladium-catalyzed highly regioselective mono and double Sonogashira cross-coupling reactions of 5-substituted-1,2,3-triiodobenzene under ambient conditions.

An efficient synthesis of 2,3-diiodinated diphenylacetylene and iodinated -terphenylacetylene derivatives through highly regioselective mono and double Sonogashira cross-coupling reactions of 5-substituted-1,2,3-triiodobenzene is reported. Significantly, the regioselectivity of coupling reactions is exclusively performed at the terminal C-I bonds, the less sterically hindered and the most regioactive positions. The highest isolated yields were achieved from reactions of electron-poor/neutral 1,2,3-triiodoarene and electron-rich arylacetylene derivatives.

The -glycan structures of the antigenic variants of chlorovirus PBCV-1 major capsid protein help to identify the virus-encoded glycosyltransferases.

The chlorovirus chlorella virus 1 (PBCV-1) is a large dsDNA virus that infects the microalga NC64A. Unlike most other viruses, PBCV-1 encodes most, if not all, of the machinery required to glycosylate its major capsid protein (MCP). The structures of the four -linked glycans from the PBCV-1 MCP consist of nonasaccharides, and similar glycans are not found elsewhere in the three domains of life.

Effect of nature of electrolytes on retention and selectivity in hydrophilic interaction liquid chromatography.

This work investigates the selectivity and retention changes on four classes of HILIC columns upon addition of 1-20 mM electrolyte. The effect of four electrolytes (NaCl, NaClO, NaPF, and NaCFCO) were tested on neutral, cationic, anionic, and zwitterionic analytes under HILIC conditions (70-90% ACN). These electrolytes alter the retention and selectivity on silica, zwitterionic and diol columns through ion exchange and ionic screening mechanisms.

Nickel as a Lewis Base in a T-Shaped Nickel(0) Germylene Complex Incorporating a Flexible Bis(NHC) Ligand.

Flexible, chelating bis(NHC) ligand 2, able to accommodate both cis- and trans-coordination modes, was used to synthesize (2)Ni(η -cod), 3. In reaction with GeCl , it produced (2)NiGeCl , 4, featuring a T-shaped Ni and a pyramidal Ge center. Complex 4 could also be prepared from [(2)GeCl]Cl, 5, and Ni(cod) , in a reaction that formally involved Ni-Ge transmetalation, followed by coordination of the extruded GeCl moiety to Ni.

1-C-phosphonomethyl- and 1-C-difluorophosphonomethyl-1,4-imino-l-arabinitols as Galf transferase inhibitors: A comparison.

The convenient preparation of iminopentitol derivatives, based on a 1,4-dideoxy-1,4-imino-l-arabinitol scaffold carrying β-phosphono(difluoromethyl) or β-phosphonomethyl appendages, as Galf-1P mimics, is reported. The compounds were tested for their ability to inhibit GlfT2, a vital galactofuranosyltransferase involved in the cell wall biosynthesis of mycobacteria. Interestingly, the Galf-1P mimics lacking a fluorine atom (7 and 8) were very poor inhibitors, showing less than 20% inhibition of GlfT2, whereas compounds 2 and 3, which contains a difluoromethylenephosphonate moiety were more potent inhibitors.

Linear solvation energy relationship (LSER) characterization of the normal phase retention mechanism on hypercrosslinked polystyrenes.

Linear solvation energy relationships (LSERs) were applied to retention on hypercrosslinked polystyrene on silica (HC-Tol) to elucidate the type and relative importance of molecular interactions between model solutes and the HC-Tol stationary phase. Classical amino phase and another hypercrosslinked phase (5-HGN) were used as reference columns. On both the HC-Tol and amino, polar interactions predominate and contribute to retention.

One-Pot Generation of Bicyclo[3.1.0]hexanols and Cyclohexanones by Double Interrupted Nazarov Reactions.

Organoaluminum-mediated double interrupted Nazarov cyclization to access bicyclo[3.1.0]hexanols via nucleophilic methyl attack followed by Simmons-Smith-type electrophilic cyclopropanation is reported.

Methylammonium Cation Dynamics in Methylammonium Lead Halide Perovskites: A Solid-State NMR Perspective.

In light of the intense recent interest in the methylammonium lead halides, CHNHPbX (X = Cl, Br, and I) as sensitizers for photovoltaic cells, the dynamics of the methylammonium (MA) cation in these perovskite salts has been reinvestigated as a function of temperature via H, N, and Pb NMR spectroscopy. In the cubic phase of all three salts, the MA cation undergoes pseudoisotropic tumbling (picosecond time scale). For example, the correlation time, τ, for the C-N axis of the iodide salt is 0.

Evidence for heterolytic cleavage of a cyclic oxonium ylide: implications for the mechanism of the Stevens [1,2]-shift.

Formation and rearrangement of several oxonium ylides containing cyclopropylcarbinyl migrating groups were studied. Efficient ring-contraction by [1,2]-shift to form cyclopropane-substituted cyclobutanones was observed, with no competing cyclopropane fragmentation. Substitution with the hypersensitive mechanistic probe (trans,trans-2-methoxy-3-phenylcyclopropyl)methyl led to cyclopropane fragmentation via an apparent heterolytic pathway, providing the first evidence for ion pair intermediates from ylide cleavage, and suggesting a possible alternative heterolytic mechanism for the Stevens [1,2]-shift.

Epitope mapping of histo blood group antigens bound to norovirus VLPs using STD NMR experiments reveals fine details of molecular recognition.

Attachment of human noroviruses to histo blood group antigens (HBGAs) is thought to be critical for the infection process. Therefore, we have determined binding epitopes of synthetic type 1 to 6 blood group A- and B-tetrasaccharides binding to GII.4 human Norovirus virus like particles (VLPs) using STD NMR experiments.

Linear solvation energy relationships in normal phase chromatography based on gradient separations.

Coupling the modified Soczewiñski model and one gradient run, a gradient method was developed to build a linear solvation energy relationship (LSER) for normal phase chromatography. The gradient method was tested on dinitroanilinopropyl (DNAP) and silica columns with hexane/dichloromethane (DCM) mobile phases. LSER models built based on the gradient separation agree with those derived from a series of isocratic separations.

High pH instability of quaternary ammonium surfactant coatings in capillary electrophoresis.

The two-tailed cationic surfactant dioctadecyldimethyl ammonium bromide (DODAB) produces semi-permanent coatings that yield strongly reversed electroosmotic flow (EOF), for example -0.31 ± 0.01 cm kV s at pH 3.

Oxidation-Initiated Cyclizations of Pentadienyl Ethers: An Alternative Entry to the Nazarov Reaction.

Oxidation-initiated Nazarov reactions of 1,4-pentadien-3-yl ethers take place in the presence of DDQ. Termination by regioselective elimination preserves both stereocenters created during electrocyclization, providing cyclopentanone products bearing an exocyclic methylene unit. Use of catalytic DDQ with MnO as terminal oxidant is also described.

Interrupting the Nazarov Cyclization with Bromine.

The generation of dibrominated cyclopentenones via an interrupted Nazarov cyclization is reported. The installation of two bromine atoms occurs at the α and α' positions of the cyclopentenyl scaffold via successive nucleophilic and electrophilic bromination of the 2-oxidocyclopentenyl cation and its resulting enolate. Notably, the reaction proceeds with good diastereoselectivity, favoring the symmetrical product.