Precursors Of Analogues Research Articles

Knower–guesser differentiation in ravens: others' viewpoints matter

Differentiating between individuals with different knowledge states is an important step in child development and has been considered as a hallmark in human evolution. Recently, primates and corvids have been reported to pass knower-guesser tasks, raising the possibility of mental attribution skills in non-human animals. Yet, it has been difficult to distinguish 'mind-reading' from behaviour-reading alternatives, specifically the use of behavioural cues and/or the application of associatively learned rules. Here, I show that ravens (Corvus corax) observing an experimenter hiding food are capable of predicting the behaviour of bystanders that had been visible at both, none or just one of two caching events. Manipulating the competitors' visual field independently of the view of the test-subject resulted in an instant drop in performance, whereas controls for behavioural cues had no such effect. These findings indicate that ravens not only remember whom they have seen at caching but also take into account that the other's view was blocked. Notably, it does not suffice for the birds to associate specific competitors with specific caches. These results support the idea that certain socio-ecological conditions may select for similar cognitive abilities in distantly related species and that some birds have evolved analogous precursors to a human theory-of-mind.

ChemInform Abstract: Synthesis of the 3-Aza(9)metacyclophane System by Oxidative Cleavage of a 3-Aza(6)(1,7)naphthalenophane Derivative.

Reaction of 10,11-dimethoxy-1,4,5,6-tetrahydro-7,9-ethano-3-benzazecine-3(2H)- carbonitrile (3) with ozone at -78°, followed by destruction of the ozonide with dimethyl sulfide, gave, in 82% yield, 15-formyl-12,13-dimethoxy-8-oxo-4-azabicyclo[9.3.1]pentadeca-1(15), 11,13-triene-4-carbonitrile (4), a representative of the new 3-aza[9] metacyclophane system. The precursor (3) was obtained by cyanogen bromide-induced eliminative ring destruction of 8,9-dimethoxy-2,3,5,6,10,11,11a,11b-octahydro-1H-benzo[de] pyrido [3,2,1-ij] quinoline (2) in 96% yield. An attempt to make the analogous precursor for the 3-aza[8] metacyclophane system was unsuccessful due to a preferred nucleophilic attack by bromide ion. Reduction of (4) with sodium tetrahydroborate gave 8-hydroxy-15-( hydroxymethyl )-12,13-dimethoxy-4- azabicyclo [9.3.1]pentadeca-1(15),11,13-triene-4-carbonitrile (5) in 79% yield.

ChemInform Abstract: Synthesis of 2,3,5-Tri-O-benzyl-D-arabinitol 1,4-Cyclic Sulfate and Its Conversion into Potential Precursors of Shikimate Substrate Analogues.

ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

ChemInform Abstract: Synthesis of Branched Chain 2-Deoxyoct-3-ulosonic Acid Derivatives as Precursors for C-Nucleoside Analogues.

Abstract Reaction of 2,3,4,5,6-penta-O-acetyl-D-galactonic 1 and D-gluconic acid chloride 2, respectively, with derivatives of malonic acid furnished substituted 2-deoxyoct-3-ulosonic acid esters, amides, and nitriles. Further modification was carried out by O-acylation and halogenation.

ChemInform Abstract: Synthesis of Precursors of Linear Thienocarbazole Analogues of Ellipticine and Olivacine.

Amides from Goldberg coupling in the benzo[b]thiophene series have been prepared as precursors of linear thienocarbazoles by ring B convergent methods of synthesis.

ChemInform Abstract: A New Access to Alkyl-α-ketoglutaric Acids, Precursors of Glutamic Acid Analogues by Enzymatic Transamination. Application to the Synthesis of (2S,4R)-4-Propyl-glutamic Acid.

Abstract 4-Alkyl-2-alkylidene-glutaric acids are easily obtained by a Claisen-Johnson rearrangement, providing a short access to 4-alkyl-α-ketoglutaric acids. These compounds are substrates of the glutamic oxalacetic transaminase (GOT), allowing the enzymatic synthesis of biologically important analogues of l -glutamate. A new analogue, (2S,4R)-4-propyl-glutamic acid, is described.

ChemInform Abstract: Nucleic Acid Related Compounds. Part 111. Glucose-Derived 3′-(Carboxymethyl)-3′-deoxyribonucleosides and 2′,3′-Lactones as Synthetic Precursors for Amide-Linked Oligonucleotide Analogues.

ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

Solvent-free microwave-assisted multi-component reaction for preparation of 2-amino-1-aryl-2-(cyclohex-1-enyl)ethanones as precursors of pseudoephedrine analogues

Microwave irradiation of chloroacetylarenes and enamines induced an aza-Darzens reaction followed by rearrangement of the aziridinium intermediate to give (2-amino-3-alkenoyl)arenes that were reduced selectively to syn-beta-aminoalcohols as pseudo-ephedrine analogues.

Fluorinated enamines of nucleobases as precursors of nucleoside analogues. Synthesis, spectroscopic and structural studies

The 1H and 19F NMR spectra of N-α-fluoro-β-trifluoromethylenamines and isostructural N-β-fluoro-β-trifluoromethylenamines of nucleobases dissolved in CDCl3 and DMSO-d6 have shown distinct differences associated with the conformational conversion between the Z and E stereoisomers. In the E stereoisomer the tetrafluoropropenyl group is rotated relative to the heteroring plane, whereas the Z stereoisomer assumes the most planar structure. The flat conformation of the Z stereoisomer is stabilised by internal hydrogen bonding between Cα–H and the carbonyl oxygen (pyrimidinic bases) or the endocyclic nitrogen (purinic bases). Large variations in the magnitudes of the chemical shifts of Cβ–H, Cα–F, C6–H and C8–H were observed, i.e. the chemical shift increased with increasing polarity and ability of DMSO-d6 to establish intermolecular hydrogen bonds in competition with intramolecular hydrogen bonds. The (Z)-N4-benzoyl-N1-(1,3,3,3-tetrafluoroprop-1-enyl)cytosine crystals undergo a phase transition at 230 K induced by the tetrafluoropropenyl substituent reorientations. Between 300 and 230 K the molecules are present in two conformations, and below 230 K the molecules gradually assume five conformations, remaining in a stable equilibrium with intermolecular forces, evidenced by single-crystal X-ray diffraction.

Intramolecular 1,3-dipolar cycloaddition of N-alkenyl nitrones en route to glycosyl piperidines

Stereoselective intramolecular 1,3-dipolar cycloaddition of homochiral N-(alkenylglycosyl)nitrones, prepared by allylation of C-(glycosyl)nitrones and subsequent oxidation, is described. The previously described 2-aza-Cope rearrangement was not observed for these substrates, but evidences of E/ Z isomerism during the cycloaddition were obtained. The obtained cycloadducts can serve as key precursors of imino disaccharide analogues. This is exemplified by a short route to a protected 2-furanosyl-4-hydroxy-6-phenyl piperidine.

Chemical synthesis of nucleoside H-boranophosphonates and their application as precursors of P-modified nucleotide analogues

Nucleoside H-boranophosphonates were synthesized via the condensation reactions of appropriately protected nucleosides with monopyridinium H-boranophosphonate and subsequent deprotection under basic conditions. 3',5'-O-Protected dinucleoside H-boranophosphonates were also synthesized via the condensation of the corresponding 5'-O-protected nucleoside 3'-H-boranophosphonates with 3'-O-protected nucleosides. A study on the chemical properties of the resultant dinucleoside phosphate analogues revealed that the P-H group could be further modified under anhydrous basic conditions.

Modulation of Carbene Spin State Population through Precursor Photophysics

Dicarbomethoxycarbene can be generated by photolysis of S-C sulfonium ylides derived from thiophene. By manipulating the thiophene (leaving group) portion of the ylide, the initial spin distribution of the carbenes can be strongly influenced. With certain carbene traps, product distributions from dicarbomethoxycarbene depend on the initial spin state distribution in which the carbene is generated and this is used as a means to report on the initial spin state distributions. This approach should be general for other carbenes generated from analogous precursors.

A Novel and Convenient Protocol for Synthesis of Pyridazines

A new flexible strategy for the synthesis of diversely functionalized pyridazines from 4-chloro-1,2-diaza-1,3-butadienes and active methylene compounds is reported. The high chemoselectivity of this approach offers access to structural precursors of GABA-A antagonist analogues.

Plasmodium berghei: Lack of antimalarial activity of an analogue of folate precursor, 2,4-diamino-6-hydroxymethylpteridine in a mouse model

It was earlier hypothesized that the malarial parasite may convert precursors of folate analogues to synthesize de novo inhibitors toxic to itself, but not to the mammalian cell. It was suggested that one such analogue, 2,4-diamino-6-hydroxymethylpteridine (DAP) may be converted to aminopterin (AMP), a known dihydrofolate reductase inhibitor. In the present study, we evaluated the ability of DAP to inhibit proliferation of Plasmodium berghei NK65 in mice, with(out) folinic acid rescue. Cumulative dosages of DAP ranging from 0.1 to 20 mg/kg bw. administered either orally or intraperitoneally showed no suppression of parasite growth, or gave mild activities that were not statistically significant ( P > 0.05). Our findings do not seem to support the hypothesis of selective de novo metabolism of DAP to AMP by the malarial parasite.

Synthesis of biomimetic precursors of isovelleral analogues

Based on how the mushroom Lactarius vellereus converts an inactive precursor into the cytotoxic dialdehyde isovelleral (1) via a cyclic enol ether, as part of a binary chemical defense system that protects the fruit bodies against parasites, a synthetic way to obtain analogous dialdehydes masked in the same way has been developed. As isovelleral analogues (e.g. 2 and 3) possess extremely potent cytotoxic activity, but display low selectivity as their biological activity is linked to their reactivity, suitably masked isovelleraloids that are converted to the corresponding dialdehyde under specific conditions, may constitute a way to utilize these potent compounds. Specifically, compounds 4 and 5, biomimetic precursors of the isovelleral analogues 2 and 3, but trapped as the stable methyl acetals, have been prepared. (Less)

Importance of the Solvent-Exposed Residues of the Insulin B Chain α-Helix for Receptor Binding

Conjointly, the solvent-exposed residues of the central alpha-helix of the B chain form a well-defined ridge, which is flanked and partly overlapped by the two described insulin receptor binding surfaces on either side of the insulin molecule. To evaluate the importance of this interface in insulin receptor binding, we developed a new powerful method that allows us to introduce all the naturally occurring amino acids into a given position and subsequently determine the receptor binding affinities of the resulting insulin analogues. The total amino acid scanning mutagenesis was performed at positions B9, B10, B12, B13, B16, and B17, and the vast majority of the insulin analogue precursors were expressed and secreted in amounts close to that of the wild-type (human insulin) precursor. The analogue binding data revealed that positions B12 and B16 were the two positions most affected by the amino acid substitutions. Interestingly, the receptor binding affinities of the B13 analogues were also markedly affected by the amino acid substitutions, suggesting that GluB13 indeed is a part of insulin's binding surface. The B10 library screen generated analogues covering a wide range of (20-340%) of relative binding affinities, and the results indicated that a structural stabilization of the central alpha-helix and thereby a more rigid presentation of the binding epitope at the insulin receptor is important for receptor recognition. In conclusion, systematic amino acid scanning mutagenesis allowed us to confirm the importance of the B chain alpha-helix as a central recognition element serving as a linker of a continual binding surface.

Synthesis of Glycosyl Boranophosphates and Their Applications as Precursors of Glycosyl Phosphate Analogues

Glycosyl boranophosphate triesters were synthesized via a boranophosphorylation of reducing sugars. The usefulness of the resultant glycosyl boranophosphates as versatile chemically stable precursors of various glycosyl phosphate derivatives is demonstrated.

Low pressure MOCVD of Er 2O 3 and Gd 2O 3 films

In this paper, we present a comparative study of microstructure, crystallinity, and physical properties of MOCVD-grown Er 2O 3 and Gd 2O 3 films, which are grown under identical conditions and using analogous precursors. They are characterized by the variety of techniques for their structure and properties. As-grown films were polycrystalline. Incorporation of heteroatomic species into the film's matrix, such as carbon, was dependent onto the oxides types and film's growth conditions. Er 2O 3 film displays 5.8 eV and Gd 2O 3 film exhibit 5.4 eV bandgap. Electrical characterizations show that the as-grown films were leaky. Thin films of Er 2O 3 display similar properties as observed in their thick counterparts, which manifest that it is possible to scale down these films for potential uses.

Nanosized Au4Pd28(CO)22(PMe3)16 Containing 32-Atom Au4Pd28 Core-Geometry with Nearly Regular Encapsulated Au4 Tetrahedron: Proposed Multitwinned-Composite Growth-Pattern Involving Four Interpenetrating Au-Centered Cuboctahedral-Based Three-Layer (Pd3)A(AuPd6)B(Au3)C Polyhedra

Our synthetic exploratory efforts to obtain new nanosized Au–Pd carbonyl/phosphine clusters by use of the trimethylphosphine precursor Pd10(CO)12(PMe3)6 with smaller-sized PMe3 ligands (versus precursors with relatively larger PEt3 ligands) have previously produced via reaction with Au(SMe2)Cl an unusual Au4Pd32(CO)28(PMe3)14 (2) containing a pseudo-D2 36-atom Au4Pd32 core-geometry with a highly distorted encapsulated Au4 tetrahedron. Herein we report a striking illustration that analogous precursors under different reaction conditions have given rise to another new type of Au–Pd cluster, Au4Pd28(CO)22(PMe3)16 (1), that not only has a completely dissimilar Au4Pd28 core-geometry with a nearly regular encapsulated Au4 tetrahedron but also a totally different postulated multitwinned-composite growth-pattern. This extraordinary cluster, which was obtained from the reaction of Pd10(CO)12(PMe3)6 with Au(PPh3)Cl or Au(SMe2)Cl (estimated yield, ∼20–40%), has a 32-atom Au4Pd28 framework that roughly conforms to cubic T (23) symmetry that is maintained by inclusion of the 16 PMe3 P atoms but is completely reduced to general C1 (1) symmetry by inclusion of the 22 bridging CO ligands. 1 was isolated under different crystallization conditions to give two solvated crystal forms: namely, 1a as diisopropyl-solvated triclinic ( $$\hbox{P}\bar 1 $$ with Z = 2), and 1b as THF/hexane-solvated monoclinic (P2/c with Z = 4). A comparative analysis of resulting low-temperature CCD X-ray diffractometry determinations revealed an amazing molecular similarity between the actual shapes of the highly deformed Au4Pd28 architectures and ligand connectivities of 1 within the two dissimilar crystal structures. These results clearly indicate that the large observed localized geometrical distortions of 1 are primarily induced by intracluster strain-releasing effects and not by crystal-packing interactions. We propose a multitwinned growth-pattern of its Au4Pd28 core involving the formation of a Au4Pd24 composite-twinned framework formed from four markedly deformed interpenetrating three-layer Au-centered (Pd3)A(Au(n)Pd6)B(Au3)C cuboctahedra (n = 1–4) that are oriented along the four localized threefold axes of the Au4 tetrahedron. The other four outermost (external) Pd atoms that are tetrahedrally disposed about the Au4Pd24 composite presumably provide stabilization by face-condensations (i.e., three tetracapped, one tricapped). This new type of multitwinned bimetallic cluster has direct relevance to both ligated and non-ligated (bare) non-crystalline metal nanoparticles, of which many have been postulated to be multitwinned.

An asymmetric approach to the radiosynthesis of both enantiomers of α-[11C]methyldopa and α-[11C]methyltyrosine for positron emission tomography

In PET, α-methyl amino acids can play a dual role: a) precursors of neurotransmitters analogues for the study of neurodegenerative diseases; b) non-metabolised analogues of proteinogenic amino acids for the study of amino acids uptake into normal and cancer cells. The difference in the uptake rates during a PET scan could visualise cancer cells in a human body. Clinical applications of such amino acids are strongly limited due to their poor availability. For the synthesis of α-[11C]methyl-tryptohan, an industrial procedure was adopted. All attempts to prepare enantiomerically pure α-[11C]methylated tyrosine failed. We carried out [11C]methylation of metalocomplex synthons derived from protected DOPA or tyrosine. Individual diastereomers were successfully separated by preparative HPLC, diluted with excess of water and extracted on C18 cartridges. Optimisation of the procedure followed by hydrolysis of the complexes and purification of the enantiomers of α-[11C]methylDOPA and α-[11C]methyltyrosine is underway.