On the structure of dithizone

The ¹³C NMR spectrum of dithizone, unlike that of its oxygen analogue, shows only five different types of carbon atom. The ¹³C chemical shift of the C?S group in dithizone is only 7 ppm to lower field of that of the C?O moiety in its analogous compound. The results can be rationalized by consideration of tautomeric equilibria which lead to C_2v time-averaged symmetry.     

Preparation of N-[11C]methyl-2,5-dimethoxy-4-methylamphetamine

In order to evaluate the neurobiological mechanism causing the psychogenic effects of N-methyl-2,5-dimethoxy-4-methylamphetamine (MDOM), the¹¹C labelled analogue was prepared for application in in vivo PET studies by the reaction of 2,5-dimethoxy-4-methylamphetamine (DOM) with [¹¹C]CH₃I. The radiochemical yield was determined in dependence on time, temperature, solvent and amount of substrate. The best conditions for fast labelling reactions with¹¹C on a preparative scale were found to be a reaction time of 10 miutes at 110°C using 1 mg DOM in acetonitrile thus obtaining radiochemical yields of 80% (based on produced [¹¹C]CH₃I).     

The 1H and 13C nmr spectra of the “onium” salts of dithiacyclophanes

The ¹H and ¹³C nmr spectra of three cyclic sulphonium salts ol dithiacyclophanes have been recorded and compared with those of the open-chain analogue. The ¹H spectra indicate that methylation of the dithiacyclophanes gives a mixture of eonformational isorners with slightly different chemical shifts for the benzylic protons. The ¹³C spectra indicate that the smaller rings adopt an unsymmetrical conformation with respect to the aromatic ring but that in the larger ring studied, the aromatic carbon atoms are magnetically equivalent. The relevance of these results to the reactivity of the aromatic ring is discussed.     

Preparation of 125I-Lanreotide and its biodistribution in murine model of melanoma

Lanreotide, a somatostatin analogue, was radioiodinated with ¹²⁵I to explore the possibility of using ¹²³I labeled lanreotide as a diagnostic radiopharmaceutical for tumors overexpressing somatostatin (SST) receptors. Radioiodination was carried out with ¹²⁵I using chloramine T as the oxidant. The labeling yield was >90%. Characterization of ¹²⁵I-Lanreotide was carried out by paper electrophoresis as well as HPLC. ¹²⁵I-Lanreotide was purified by chromatography using a C18 Sep-Pak column. Radiochemical purity of the purified ¹²⁵I-Lanreotide thus obtained was >99%. Significant tumor uptake of ¹²⁵I-Lanreotide was observed in C57BL/6 mice bearing melanoma.     

Substitution of an Internal Disulfide Bridge with a Diselenide Enhances both Foldability and Stability of Human Insulin

Insulin analogues, mainstays in the modern treatment of diabetes mellitus, exemplify the utility of protein engineering in molecular pharmacology. Whereas chemical syntheses of the individual A and B chains were accomplished in the early 1960s, their combination to form native insulin remains inefficient because of competing disulfide pairing and aggregation. To overcome these limitations, we envisioned an alternative approach: pairwise substitution of cysteine residues with selenocysteine (Sec, U). To this end, Cys^A6 and Cys^A11 (which form the internal intrachain A6–A11 disulfide bridge) were each replaced with Sec. The A chain[C6U, C11U] variant was prepared by solid-phase peptide synthesis; while sulfitolysis of biosynthetic human insulin provided wild-type B chain-di-S-sulfonate. The presence of selenium atoms at these sites markedly enhanced the rate and fidelity of chain combination, thus solving a long-standing challenge in chemical insulin synthesis. The affinity of the Se-insulin analogue for the lectin-purified insulin receptor was indistinguishable from that of WT-insulin. Remarkably, the thermodynamic stability of the analogue at 25 °C, as inferred from guanidine denaturation studies, was augmented (ΔΔG_u ≈0.8 kcal mol⁻¹). In accordance with such enhanced stability, reductive unfolding of the Se-insulin analogue and resistance to enzymatic cleavage by Glu-C protease occurred four times more slowly than that of WT-insulin. 2D-NMR and X-ray crystallographic studies demonstrated a native-like three-dimensional structure in which the diselenide bridge was accommodated in the hydrophobic core without steric clash.     

Tricarbonyl (triquinacene)-molybdenum and-tungsten

Triquinacene reacts with hexacarbonylmolybdenum to give tricarbonyl(triquinacene)molybdenum, and with tris(acetonitrile)tricarbonyltungsten to give tricarbonyl(triquinacene)tungsten, whereas efforts to synthesize the corresponding chromium complex, tricarbonyl(triquinacene)chromium, were unsuccessful.The molybdenum complex was characterized by ¹H and ¹³C NMR spectroscopy, mass spectra, and a single crystal X-ray structure determination. The tungsten complex is thermally less stable and more susceptible to oxidation than its molybdenum analogue and was characterized by the mass spectrum and the ¹H NMR spectrum. The crystal structure of the tricarbonyl(triquinacene)molybdenum is compared to that for the free ligand. Besides the expected lengthening of the CC bonds, the complex shows a deepening of the triquinacene “basket”, presumably to give better overlap of the CC bonds with molybdenum orbitals.     

Cycloaddition of alkynes RCCR′ with free singlet dimethyl germylene Me2Ge

Alkynes RCCR′ exhibit a high and specific reactivity towards free dimethyl germylene Me₂Ge as a typical singlet heavy carbene analogue. New and novel unsaturated² 4-,5-, and 6-membered germa heterocycles with 1–3 Ge atoms are formed, dependent on R and R′ in the 7 alkynes used. Corresponding reaction mechanisms are proposed.     

Synthesis,characterization, and evaluation of antimicrobial activities of a new class of macrocyclic phosphonates

A series of a new class of phosphorus analogue macrocycles was accomplished by condensation of N‐substituted‐[bis(3,5‐dimethyl‐2‐hydroxybenzyl)]‐amines with various phosphorus dichlorides in dry toluene in the presence of triethylamine at 0–50°C. All the title compounds were evaluated for antimicrobial activity to determine their efficacy and were effective in suppressing the growth of bacteria and fungi. The chemical structures of the title products were characterized by IR, ¹H, ¹³C, ³¹P‐NMR, mass spectral studies, and elemental analysis. J. Heterocyclic Chem., (2011).     

Copper‐Catalyzed C(sp3)−H/C(sp3)−H Cross‐Dehydrogenative Coupling with Internal Oxidants: Synthesis of 2‐Trifluoromethyl‐Substituted Dihydropyrrol‐2‐ols

The first oxidative C(sp³)−H/C(sp³)−H cross‐dehydrogenative coupling (CDC) reaction promoted by an internal oxidant is reported. This copper‐catalyzed CDC reaction of oxime acetates and trifluoromethyl ketones provides a simple and efficient approach towards 2‐trifluoromethyldihydropyrrol‐2‐ol derivatives in a highly diastereoselective manner by cascade C(sp³)−C(sp³) bond formation and cyclization. These products were further transformed into various significant and useful trifluoromethylated heterocyclic compounds, such as trifluoromethylated furan, thiophene, pyrrole, dihydropyridazine, and pyridazine derivatives. A trifluoromethylated analogue of an Aβ₄₂ lowering agent was also synthesized smoothly. Preliminary mechanistic studies indicated that this reaction involves a copper(I)/copper(III) catalytic cycle with the oxime acetate acting as an internal oxidant.     

The Dimroth rearrangement as a probable cause for structural misassignments in imidazo[1,2-a]pyrimidines: A 15N-labelling study and an easy method for the determination of regiochemistry

Structural misassignments are often seen for complex natural products, but this can also be an issue with seemingly simpler structures. In this paper, we describe how, using a ¹⁵N-labelled analogue, we established that the Dimroth rearrangement can occur in imidazo[1,2-a]pyrimidines and result in an incorrect regiochemical assignment of such compounds. These studies supported a rearrangement mechanism involving addition of hydroxide ion followed by ring opening. It was also observed that C(2) and C(3) substituted regioisomers could be readily distinguished using ¹H NMR spectroscopy.     

Activation of a Carbon–Oxygen Bond of Benzofuran by Precoordination of Manganese to the Carbocyclic Ring: A Model for Hydrodeoxygenation

Stable unsaturated heterocycles such as benzofuran are difficult to remove from petroleum by conventional catalytic hydrotreating. However, in a model system, coordination of Mn(CO)₃⁺ to the aromatic ring of benzofuran activates the C−O bond towards insertion of [Pt(PPh₃)₂] [Eq. (1)]. The insertion is preceded by precoordination to the furan C=C bond; thus, the 2,3-dihydro analogue of 1 , which lacks this double bond, does not undergo insertion of the Pt moiety.     

Discrimination of pseudo‐meta and pseudo‐para diamino‐octafluoro[2.2]paracyclophanes by 1H, 19F,and 13C NMR

Pseudo‐meta and pseudo‐para diamino‐octafluoro[2.2]paracyclophanes are challenging to separate either by chromatography or recrystallization, but through the use of a mixture of the two isomers, the ¹H, ¹⁹F, and ¹³C NMR spectra of these compounds have been fully and unambiguously assigned using ¹H COSY, ¹H‐¹⁹F HOESY, ¹H‐¹³C HSQC, ¹H‐¹³C HMBC, and ¹⁹F‐¹³C HSQC techniques. This permits the easy identification of either of the individual isomers. In addition, the ¹³C spectrum of the pseudo‐ortho analogue is reported and assigned for the first time. The gem shift effect in this series of bridge‐fluorinated paracyclophanes serves to deshield ¹H resonances and shield ¹³C. Copyright © 2012 John Wiley & Sons, Ltd.     

Hydrogen‐Bonding Pincer Complexes with Two Protic N‐Heterocyclic Carbenes from Direct Metalation of a 1,8‐Bis(imidazol‐1‐yl)carbazole by Platinum,Palladium, and Nickel

Pincer protic N‐heterocyclic carbene (PNHC) complexes were synthesized by direct metalation, the formation of a metal carbon bond from an unfunctionalized C?H bond in a single synthetic step. Significantly, direct metalation succeeded even for a first‐row metal, nickel. The chloride complexes were isolated and then converted to the acetate, triflate, or in the platinum case, a hydride analogue. Crystal structures and ¹H, ¹³C, and ¹⁵N NMR data, as well as IR spectra, document the effects of intramolecular hydrogen bonding and the planar but flexible pincer framework. Anti‐Markovnikov addition of O?H bonds to alkynes, including catalyzed alkyne hydration, were demonstrated on the Pt triflate analog.     

Impact of Oxidation State on Reactivity and Selectivity Differences between Nickel(III) and Nickel(IV) Alkyl Complexes

Described is a systematic comparison of factors impacting the relative rates and selectivities of C(sp³)?C and C(sp³)?O bond‐forming reactions at high‐valent Ni as a function of oxidation state. Two Ni complexes are compared: a cationic octahedral Ni^IV complex ligated by tris(pyrazolyl)borate and a cationic octahedral Ni^III complex ligated by tris(pyrazolyl)methane. Key features of reactivity/selectivity are revealed: 1) C(sp³)?C(sp²) bond‐forming reductive elimination occurs from both centers, but the Ni^III complex reacts up to 300‐fold faster than the Ni^IV, depending on the reaction conditions. The relative reactivity is proposed to derive from ligand dissociation kinetics, which vary as a function of oxidation state and the presence/absence of visible light. 2) Upon the addition of acetate (AcO^?), the Ni^IV complex exclusively undergoes C(sp³)?OAc bond formation, while the Ni^III analogue forms the C(sp³)?C(sp²) coupled product selectively. This difference is rationalized based on the electrophilicity of the respective M?C(sp³) bonds, and thus their relative reactivity towards outer‐sphere S_N2‐type bond‐forming reactions.     

Synthesis of chiral building blocks for cephalostatin analogues

The present paper describes the synthesis of 5‐azido‐6‐ketones (14) and 6‐hydroxy‐5‐ketone (20) from Hajos Wiechert ketone as chiral building blocks for cephalostatin analogues. The synthesis of symmetric cephalostatin analogue from 6‐hydroxy‐5‐ketone has also been reported. The characterization of the each synthesized compounds was carried out by IR, ¹H‐NMR, ¹³C‐NMR and High resolution Mass Spectrometry.     

Oxidation of a P−C Bond under Mild Conditions

The reactivity of phosphenium dication [(Ph₃P)₂C‐P‐NiPr₂]²⁺, 1²⁺ , towards pyridine N‐oxide (O‐py) has been investigated. The resulting oxophosphonium dication [(Ph₃P)₂C(NiPr₂)P(O)(O‐py)]²⁺, 2²⁺ , was surprisingly stabilized by a less nucleophilic O‐py ligand instead of pyridine (py). This compound was then identified as an analogue of the elusive Criegee intermediate as it underwent oxygen insertion into the P?C bond through a mechanism usually observed for Baeyer–Villiger oxidations. This oxygen insertion appears to be the first example of a Baeyer–Villiger oxidation involving O‐py.     

Bioluminescent properties of obelin and aequorin with novel coelenterazine analogues

The main analytical use of Ca²⁺-regulated photoproteins from luminous coelenterates is for real-time non-invasive visualization of intracellular calcium concentration ([Ca²⁺]_i) dynamics in cells and whole organisms. A limitation of this approach for in vivo deep tissue imaging is the fact that blue light emitted by the photoprotein is highly absorbed by tissue. Seven novel coelenterazine analogues were synthesized and their effects on the bioluminescent properties of recombinant obelin from Obelia longissima and aequorin from Aequorea victoria were evaluated. Only analogues having electron-donating groups (m-OCH₃ and m-OH) on the C6 phenol moiety or an extended resonance system at the C8 position (1-naphthyl and α-styryl analogues) showed a significant red shift of light emission. Of these, only the α-styryl analogue displayed a sufficiently high light intensity to allow eventual tissue penetration. The possible suitability of this compound for in vivo assays was corroborated by studies with aequorin which allowed the monitoring of [Ca²⁺]_i dynamics in cultured CHO cells and in hippocampal brain slices. Thus, the α-styryl coelenterazine analogue might be potentially useful for non-invasive, in vivo bioluminescence imaging in deep tissues of small animals.     

13C-13C NMR coupling constants in substituted allylic ion-pairs of the type occurring in anionic diene polymerization

¹³C-¹³C NMR coupling constants have been measured on the 1:1 adduct of tert-butyllithium and butadiene, a model for the active centres in the anionic polymerization of butadiene. Solutions in three solvents in which solvation and aggregation properties differ were studied, tetrahydrofuran, diethyl ether and benzene. The 2-methyl- substituted analogue, more appropriate for isoprene type systems was also converted to the potassium salt and a comparison was made of the effect of counter ion. Ion-pair structure is discussed in terms of these measurements.     

The synthesis of a novel trimetallic complex containing three redox centres and an assessment of inductive effect transmission through an iron atom

The novel trimetallic complex [Fe{η⁵-C₅H₄SMo(NO)LCl}₂]; in which L = tris(3,5-dimethylpyrazolyl)hydroborate, and its bimetallic analogue [{(Mo(NO)LCl)}₂(m-S₂C₆H₄)] have been synthesised; electrochemical studies of these compounds indicate that the inductive effects of the molybdenum-containing substituent are transmitted to equal extents through the CFeC and CCC bridging atom chains.     

13C-NMR-spektren von bicyclo[n.1.0]alkenen

The ¹³C-NMR spectra of some bicyclo[3.1.0]hex-3-en-2-ols and of some bicyclo[3.1.0]hex-3-en-2-ones are described. The bond parameters of bicyclo[3.1.0]hex-3-en-2-one are derived from a structure determination of endo-6-methoxy-1,3,6-triphenylbicyclo[3.1.0]hex-3-en-2-one. The electron density is calculated by the EHT method, and correlated with the ¹³C NMR shifts. For comparison the ¹³C NMR spectrum of a bicyclo[4.1.0]hepta-1,5-dione derivative is analysed. The influence of a cyclopropane system attached to a five-membered and to a six-membered ring is elucidated. Whereas the five-membered ring shows conjugation between the carbonyl group and the cyclopropane system, the same effect is not observed in the six-membered ring analogue. This is explained by the highly rigid structure of the five-membered ring.