NHC-Activations on α-, β-, γ-, and Beyond

Over the recent decades, due to the special electronic characteristics and diverse reactivities, N-heterocyclic carbene (NHC) has received significant interest in organocatalyzed reactions. The formation of Breslow intermediates by NHC can convert into acyl anion equivalent, enolates, homoenolate, acyl azolium, and vinyl enolate etc., and the cycloaddition reactions of these species has attracted lots of attention. In this review, we focus on the summry of the development of NHC-activation of carbonyl carbon (or imine carbon) in situ, α-, β-, γ-, and beyond, and the cycloaddition reaction of these species.     

Synthetic Approaches to α-, β-, γ-, and δ-Lycoranes

Lycorane is a pentacyclic core presented in alkaloids isolated from the Amaryllidaceae family of herbaceous flowering plants. Members of this class of natural products have shown to display important biological properties including analgesic, antiviral, and antiproliferative activities. This review presents the known synthetic routes toward α-, β-, γ-, and δ-lycoranes. α-(19 routes), β-(10 routes), γ-(38 routes), and δ-(6 routes).     

γ- and UV-radiation-induced degradation of sphingomyelin,lysosphingomyelin, and related compounds

The experimental data on the formation of final products in the radiolysis of 2-aminoglycerol and lysosphingomyelin (sphingosine phosphocholine) and in the photolysis of N-(2-hydroxypropyl)hexanamide and sphingomyelin suggest the occurrence of the radiation-induced degradation of the above substances with C-C bond cleavage. It was hypothesized that this process occurs by the formation and subsequent degradation of the N-centered radicals of the substrates.     

Direct Synthesis of Amphiphilic α-, β-, and γ-Cyclodextrins

ABSTRACT

The clean one step synthesis of the amphiphilic α-, β-, and γ-cyclodextrins starting from per-(6-bromo-6-deoxy)-α-, -β-, and -γ-cyclodextrins is described. The role of the lipophilic tail is played by various aryl groups (phenyl, p-bromophenyl, p-O-butoxyphenyl, p-pentylphenyl, and o-, m-, and p-nitrophenyl) linked by a thioether bridge to the position C-6 of each glucopyranose unit. The yields of the S-alkylation reactions were very high (85-95%).     

Hydrocarbon (π- and σ-) complexes of nickel,palladium and platinum: Synthesis,reactivity and applications

With the exception of metallocenes, transition metal complexes with hydrocarbon ligands only are rare. However, complexes of this type containing Group 10 metals are known and have been shown to be quite stable. These complexes are versatile precursors for many organometallic compounds. In addition, such compounds can play an important role in many reactions including C–H or C–C activation reactions and have useful applications in the thermal and photochemical production of metal films by chemical vapour deposition (CVD). The present review summarizes the synthesis, properties and chemistry of hydrocarbon complexes of Group 10 metals of the type L_nM or L_nMR₁R₂ (where L_n = σ- or π-hydrocarbon ligands; M = Ni, Pd and Pt; R₁, R₂ = σ-hydrocarbon ligands) without the involvement of any hetero donor ligands such as N, P, O and S in the metal coordination spheres.     

Host–guest interactions between niobocene dichloride and α-, β-, and γ-cyclodextrins: preparation and characterization

The possible inclusion complexes of Cp₂NbCl₂ into α-, β-, and γ-CD hosts have been investigated. The existence of a true inclusion complex in the solid state was confirmed by a combination of thermogravimetric analysis, FTIR, PXRD, and ¹³C CP-MAS NMR spectroscopies. The solid-state results demonstrated that α-cyclodextrin does not form inclusion complexes with Cp₂NbCl₂ whereas β- and γ-cyclodextrins do form such complexes. PXRD, NMR, and thermal analysis showed that the organometallic molecules of Cp₂NbCl₂OH are included in the cavities of β- and γ-cyclodextrins, possibly adopting a symmetrical conformation in the complex, with each glucose unit in a similar environment. In solution, ¹H NMR experiments suggest that niobocene has a shallow penetration on the β-CD leading to upfield shift on H-3 signal with a minor perturbation on the H-5 proton while for γ-CD, both H-3 and H-5 are shifted upfield substantially. This suggests that niobocene penetrates deeper into the γ-CD cavity than in the β-CD cavity, as a result of the cavity size. Electronic supplementary material The online version of this article (doi:) contains supplementary material, which is available to authorized users.     

Intramolecular hydrogen bond energy and cooperative interactions in α-, β-, and γ-cyclodextrin conformers

Accurate estimation of individual intramolecular hydrogen bond (H-bond) energies is an intricate task for multiply H-bonded systems. In such cases, the hydrogen bond strengths could be highly influenced by the cooperative interactions, for example, those between hydroxyl groups in sugars. In this work, we use the recently proposed molecular tailoring approach-based quantification (Deshmukh, Gadre, and Bartolotti, J Phys Chem A 2006, 110, 12519) to the extended systems of cyclodextrins (CDs). Further, the structure and stability of different conformers of α-, β-, and γ-CDs are explained based on the energetics and cooperative contribution to the strength of these H-bonds. The estimated O-H···O H-bond energies in the various CD conformers are found to vary widely from 1.1 to 8.3 kcal mol(-1). The calculated energy contributions to cooperativity toward the H-bond strengths fall in the range of 0.25-2.75 kcal mol(-1).     

Studies on α-, β-, and γ-cyclodextrin inclusion complexes of isoquinoline alkaloids berberine, palmatine and coralyne

The complexation of three isoquinoline alkaloids berberine, palmatine and coralyne with α-, β-, and γ-CDs were studied by absorption, fluorescence, circular dichroism, NMR spectroscopy and microcalorimetric assay techniques. Their binding constant (K _BH) values were determined by Benesi–Hildebrand equation. All the alkaloids formed 1:1 stoichiometry complexes with the cyclodextrins (CDs). The binding affinity is largest in β-CD followed by γ-, and α-CD for coralyne, followed by berberine and then palmatine. The thermodynamic parameters of the complexation were determined by calorimetry. The stoichiometry of complex formation and the variation of the apparent binding constant from spectroscopic studies were confirmed by calorimetry. The formation of the inclusion complexes was entropy driven in almost all the systems. Coralyne formed the strongest complex with all the CDs, followed by berberine and palmatine in that order. Coralyne-β-CD complex was studied through NMR, indicating more than one interaction mode.     

Investigation on the Interaction of Bendazac with β-, Hydroxypropyl-β-, and γ-, yclodextrins

The interactions of Bendazac, a topical non-steroidal anti-inflammatory drug, with-cyclodextrin, hydroxypropyl--cyclodextrin and -cyclodextrinwere investigated to evaluate possibilities to improve the drug's poor water solubilityand eventually to enhance the topical delivery of Bendazac. Phase solubility studiesdemonstrated the ability of the selected cyclodextrins to complex with Bendazac andincrease drug solubility. The amount of solubilized Bendazac increased linearly withthe addition of each cyclodextrin according toA_L type plots. ¹³C-NMR studiesshowed that the Bendazac A-ring was included in the cavity of the three cyclodextrins.The -cyclodextrin was also able to include the B-ring of Bendazac, forminga complex where one drug molecule fitted into two cyclodextrin molecules. Equimolarsolid systems of the drug with each cyclodextrin carrier were prepared using varioustechniques (physical mixing, spray-drying and freeze-drying). The results of differential scanning calorimetry and Fourier transform infrared analysis, performed on the solid systems, demonstrated that freeze-dried and spray-dried products had a high degree of amorphization and agreed with the hypothesis of the existence of drug–cyclodextrin interaction in the solid state. The cyclodextrins tested were able to improve the dissolution of Bendazac. The dissolution profile of the drug was also affected by the physico-chemical properties of each solid system, the freeze-dried products being the most rapidly dissolving forms.     

Interactions of amphiphilic drugs withα-,β-, andγ-cyclodextrins

The association of several amphiphilic drugs with -, -, and -cyclodextrins has been measured by use of drug-sensitive electrodes. Drugs investigated are hydrochlorides of chlorpromazine, dibucaine, tetracaine, and procaine, and valethamate bromide. Each drug forms the drug:cyclodextrin=11 complex with - and -cyclodextrin, and both the 11 and 21 complex with -cyclodextrin, except valethamate which only forms the 11 complex. The strength of the 11 complex formations is in the order of CyD>-CyD>-CyD. The association constant of the 21 complex in drug--CyD is larger than that of 11 complex. The free energy change of the conplex formation has a positive correlation with that of the micelle formation of drugs. The deviation from this relation is explained in terms of fittability of the bulky hydrophobic group of drugs into the cyclodextrin's cavity. The free energy change for the complex formation between chlopromazine or valethamate and -CyD is governed by the enthalpy term and not by the entropy term which controls the surfactant--CyD interactions.     

Reaction of aminals of conjugated unsaturated ω-dimethylaminoaldehydes with 1,2-, 1,3-, 1,4-, 1,5-, and 1,6-diketones

The condensation of aminals of -dimethylaminoacrolein and 5-dimethylaminopenta-2,4-dienal with cyclic and acyclic 1,2-, 1,3-, 1,4-, 1,5-, and 1,6-diketones was studied. A series of previously unknown bis(,-dimethylaminopolyenyl)diketones was synthesized; their structures were established by means of¹H and¹³C NMR spectroscopies. The electron absorption spectra were employed to study the mutual influence of -aminopolyene chromophores separated by two C=O groups.Translated fromIzvestiya Akademii Nauk. Seriya Khimicheskaya, No. 7, pp. 1235–1241, July, 1993.     

UV spectroscopic study of the interaction betweenα-,β-, andγ-cyclodextrins and pyridine derivatives

Complex formation between-,- and-cyclodextrins and some pyridine derivatives (hydroxy,O- andN-methyl) have been investigated by UV spectroscopy. Inclusion processes do not exert any noticeable influence on the UV absorption spectra of most of the guests which do not give rise to tautomeric equilibria or which show a strong prevalence for one of the tautomeric forms. In contrast, the equilibrium between the lactim and the lactim forms of 3-hydroxypyridine (which are present in comparable amounts in aqueous solution) was shown to be markedly affected by the inclusion process with a preferential complexation of the latter tautomer.     

Interaction of naproxen with α-, β-, and γ-hydroxypropyl cyclodextrins in solution and in the solid state

Solid combinations of naproxen with amorphous hydroxypropyl derivatives of -, -, and -cyclodextrin with an average substitution degree per anhydroglucose unit of 0.6 were investigated for thermal behaviour (differential scanning calorimetry), drug crystallinity (X-ray diffractometry), and dissolution rate (dispersed amount and rotating disc methods). Phase-solubility analysis and computer-aided molecular modelling were carried out to study the inclusion complexation of naproxen with hydroxypropyl cyclodextrins. The cavity size of the host is a selective factor for the solubilizing effect, complexing ability, and dissolution rate enhancement on naproxen, hydroxypropyl -cyclodextrin being markedly the most effective derivative. No relationship was found between the decrease in crystallinity of the drug dispersed in the amorphous carrier matrix and the geometrical features of the cyclodextrin macrocycle.     

Vibronic spectra and normal coordinate analysis of substituted anilines—I. 2,3-, 2,4-, and 2,5-dimethylanilines

Vibronic spectra of 2,3-, 2,4-, and 2,5-dimethylanilines (DMA) have been recorded in the vapor phase and analysed primarily for ascertaining the frequencies of certain low lying fundamentals (< 1000 cm⁻¹) which were observed earlier in infrared and Raman spectra with rather poor intensities. In most cases, the investigation of vibronic spectra has supported the data observed in infrared and Raman spectra. However, a new frequency has been observed at ∼120 cm⁻¹ in each molecule and has been assigned to the CNH₂ out-of-plane wag. A detailed analysis of the vibronic spectra of these three molecules revealed that an interaction-induced blue-shift of nearly 1700 cm⁻¹ is caused in the (0, 0) band of all the three DMAs due to an electrostatic interaction between the NH₂ and CH₃ groups.The normal coordinate analyses (NCA) of the above three molecules have been carried out using a general valence force field (GVFF) with 21 principal and 30 interaction force constants, assuming an averaged structure, a planar geometry, and a C_s symmetry in each case. The fundamental frequencies were mostly taken from an earlier work reported from this laboratory. Some frequencies were also picked up from the investigation of the vibronic spectra reported herein. The force field calculations were carried out using the least-squares iterative technique. During final calculations, all the 51 force constants were allowed to iterate simultaneously, which reproduced the 52 experimentally observed fundamentals out of the 54 (35a′+ 19a″) expected ones within an average error of ± 1.0% with a reasonable potential energy distribution (PED) among the various normal modes.     

Quantum chemical investigation on the structural and electronic properties of α-, β-, and γ-cyclodextrin complexes: DFT and QTAIM analysis

To characterize the structural, thermochemical and electronic aspects in complexes of leucine, vanillin and mechlorethamine with α-, β-, and γ-cyclodextrins (CDs), a density functional theory (DFT) study has been conducted in combination with quantum theory of atoms in molecules (QTAIM) analysis. The QTAIM method has been utilized to explore the nature of various possible interactions between leucine, vanillin and mechlorethamine with CDs in terms of bond critical points (BCPs). HOMO and LUMO and atomic charges studies show charge transfer occurs between drugs and cyclodextrins. This behavior has been also investigated via QTAIM charge analysis. On the other hand, based on QTAIM electronic energy indicators we have discussed electrostatic character of interactions between vanillin, leucine and mechlorethamine with inner surface CDs in the coordination sphere.     

Polymorph specific RMSD local order parameters for molecular crystals and nuclei: α-, β-, and γ-glycine

Crystal nucleation is important for many processes including pharmaceutical crystallization, biomineralization, and material synthesis. The progression of structural changes which occur during crystal nucleation are often described using order parameters. Polymorph specific order parameters have been developed for crystallization of spherically symmetric particles; however, polymorph specific order parameters for molecular crystals remain a challenge. We introduce template based polymorph specific order parameters for molecular crystals. For each molecule in a simulation, we compute the root mean squared deviation (RMSD) between the local environment around the molecule and a template of the perfect crystal structure for each polymorph. The RMSD order parameters can clearly distinguish the α-, β-, and γ-glycine polymorph crystal structures in the bulk crystal and also in solvated crystallites. Surface melting of glycine crystallites in supersaturated aqueous solution is explored using the newly developed order parameters. The solvated α-glycine crystallite has a thinner surface melted layer than the γ-glycine crystallite. α-glycine forms first out of aqueous solution, so surface melted layer thickness may provide insight into interfacial energy and polymorph selection.     

Total Syntheses of 11-Acetoxy-4-deoxyasbestinin D, 4-Deoxyasbestinin C,Asbestinin-10, -20, -21 and -23

Six members of the asbestinin family of marine diterpene natural products have been synthesized in an efficient and stereoselective manner from a single oxa-bridged intermediate. Five of these natural products have not been synthesized previously and the structures of four of them have been confirmed as those proposed originally or following revisions to the original structures. The fifth natural product—asbestinin-21—has been shown to be a diastereomer of the compound that had been proposed previously.     

A simple molecular-orbital study of theβ-,α-, and p-bands in triphenylenes

Clar has observed that the spectra of annellated derivatives of triphenylene such as II, III, IV below show remarkable resemblance to those of the phenes defined by the central ring of the triphenylene and its two longest acene limbs, II resembling tetraphene I, and III and IV pentaphene V. We show that this observation can be explained in terms of a simple modification of the Hückel molecular-orbital method.

---

Zusammenfassung Eine Beobachtung von Clar hat gezeigt, daß die Spektren der Benzologen des Triphenylens, wie z. B. II, III, IV außerordentlich ähnlich sind denen der Phene, die ausgehend vom zentralen Ring und den beiden längsten Armen der obigen Systeme gebildet werden. Daher ähnelt das Spektrum von II stark dem des Tetraphens I und die von III und IV dem des Pentaphens V. Es wird gezeigt, daß dieser Beobachtung durch eine einfache Modifikation der Hückelschen MO-Theorie Rechnung getragen werden kann.

---

Résumé Clar a observé que les spectres d'absorption des dérivés annelés du triphénylène tels que, II, III et IV montrent une ressemblance extraordinaire à ceux des phènes définis par l'anneau central du triphényléne et ses deux armes les plus longues. Ainsi le spectre de II ressemble à celui du tétraphène et ceux de III et de IV à celui du pentaphène V. Nous avons démontré qu'on peut expliquer cette observation par une modification simple de la méthode des orbitales moléculaires d'Hückel.

---

---

We gratefully acknowledge many helpful discussions with Dr. E. Clar and Dr. J.-F. Guye-Vuilléme and the award of a D. S. I. R. Maintenance Grant to one of us (D. A. M.-B.). Chemistry Department, University of Glasgow.     

Binding behaviors of scutellarin with α-, β-, γ-cyclodextrins and their derivatives

A series of cyclodextrin/scutellarin inclusion complexes were prepared from α-cyclodextrin, β-cyclodextrin and 2-hydroxypropyl-β-cyclodextrin with scutellarin (SCU), and their inclusion complexation behaviors, such as stoichiometry, complex stability constants and inclusion mode, were investigated by means of UV/Vis spectroscopy, ¹H NMR and 2D NMR. The results showed that the SCU could be efficiently encapsulated in the cyclodextrin cavity in aqueous solution to produce complexes that were more soluble than free SCU. The enhanced binding ability of cyclodextrins towards SCU was discussed from the viewpoint of the size/shape-fit and multiple recognition mechanism between host and guest.     

Steric effects in the catalytic amination of γ-, δ-, and ε-glycols

The amination of butane-1,4-diol, isomeric dipropylene glycols, and cyclohexane-1,4-diyldimethanol in the presence of nickel/copper/chromium catalysts has been studied. The effect of the initial glycol structure on the reaction selectivity has been estimated.