Introduction of functional groups into peptides via N-alkylation

An optimized protocol for the mild and selective Fukuyama-Mitsunobu reaction was used for mono- and di- N-alkylation on solid support. Thereby, nonfunctionalized aliphatic and aromatic residues are quickly introduced into transiently protected, primary amines of a linear peptide. N-Alkylation can also be used to implement alkyl chains carrying (protected) functionalities suited for subsequent modification. Applicability of this method is demonstrated by various N-alkylated analogues of a cyclic CXCR4 receptor antagonist originally developed by Fujii et. al.     

Localization of N-oxide groups by means of nitrogen chemical shifts

The applicability of nitrogen chemical shifts to the localization of N-oxide groups in azine ring systems is exemplified by 1,2,4-triazine systems. The average excitation energy approximation in the theory of magnetic shielding gives a good linear correlation with the nitrogen shieldings in azine N-oxides.     

The chlorine evolution reaction promoted by organocatalysts with amide functional groups

<正>Since the nineteenth century, the chlor-alkali process entails the electrochemical oxidation of sodium chloride solutions to Cl₂ by the chlorine evolution reaction(CER) and the simultaneous production of sodium hydroxide and H₂ at the cathode, of which sodium hydroxide and Cl₂ are widely used as important chemicals [1]. Currently, Cl₂ production relies heavily on the chlor-alkali process, which is implemented on an industrial scale worldwide,     

N-alkylation of dimethylaniline using 1,3,2-oxaphosphalenes

Conclusions 2,2,2-Trimethoxy-3,5-diphenyl-4-benzoyl-1,3,2-oxazaphospholene has alkylating properties toward dimethylaniline.Translated from Izvestiya Akademii Nauk SSSR, Seriya Khimicheskaya, No. 7, pp. 1631–1633, July, 1979.     

Acid-catalyzed N-alkylation of tosylhydrazones using benzylic alcohols

N-Alkylation of tosylhydrazones in the presence of an acid catalyst is described for the first time. Tris(pentafluorophenyl) borane was found to be a mild and efficient catalyst when benzylic alcohols were used as the alkylating agents.     

Epoxidation reaction of perfluoroalkenes with tert-amine N-oxide

Straight-chain aliphatic terr-amine N-oxides were found to be useful oxidizing agent for epoxidation of tri- and tetra-substituted perfluoroalkenes under mild conditions in high yields.The process for epoxidation by employing tri-n-butylamine N-oxide gave the best result in the reagent survey.     

Controlling a recognition-mediated reaction using a pH switch

The selective recognition-mediated reaction between a nitrone bearing a urea recognition site and a maleimide bearing a proton switchable recognition site can be turned 'on' and 'off' by the addition of base and acid respectively.     

Effects of polymer structure on reactivity of functional groups in reduction reaction using tin hydride soluble supports

The influence of macromolecular chains onto reactivity of the grafted functional group has been investigated through reduction of 6‐bromohexene using tin hydride soluble polymer supports. Kinetic investigations clearly indicate a retarding effect of the polymer structure on the substrate diffusion. Correlations of molecular weight and degree of functionalization with reactivity of the functional lateral groups are discussed. In dilute regime, an increasing of internal density of the polymer coil leads to a diminution of the rate constant k_H. Thus, the higher density of the coil limits the substrates diffusion, which favors the radical cyclization and so formation of the cyclic product. At the opposite, in concentrated regime formation of the acyclic product, hex‐1‐ene is favored despite the higher viscosity of such medium that should limit the diffusion. © 2006 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 44: 5954–5964, 2006     

Direct synthesis of functional azaxanthones by using a domino three-component reaction

NH aldimines, generated in situ from the corresponding aldehydes by reaction with ammonium acetate, serve as nitrogen nucleophiles in reactions with 3-(1-alkynyl)chromones and 3-cyanochromones that generate functionalized azaxanthones. These processes take place under mild conditions that do not require dry solvents. The products of the reactions described represent new chemical entities. We believe that the newly developed cascade process will serve as a potent method for the synthesis of N-heterocycles and in diversity-oriented synthesis.     

Calculating the knowledge-based similarity of functional groups using crystallographic data

A knowledge-based method for calculating the similarity of functional groups is described and validated. The method is based on experimental information derived from small molecule crystal structures. These data are used in the form of scatterplots that show the likelihood of a non-bonded interaction being formed between functional group A (the `central group') and functional group B (the `contact group' or `probe'). The scatterplots are converted into three-dimensional maps that show the propensity of the probe at different positions around the central group. Here we describe how to calculate the similarity of a pair of central groups based on these maps. The similarity method is validated using bioisosteric functional group pairs identified in the Bioster database and Relibase. The Bioster database is a critical compilation of thousands of bioisosteric molecule pairs, including drugs, enzyme inhibitors and agrochemicals. Relibase is an object-oriented database containing structural data about protein-ligand interactions. The distributions of the similarities of the bioisosteric functional group pairs are compared with similarities for all the possible pairs in IsoStar, and are found to be significantly different. Enrichment factors are also calculated showing the similarity method is statistically significantly better than random in predicting bioisosteric functional group pairs.     

Controlling the Scholl reaction

Guidelines for the application of the Scholl reaction were developed. Labeling experiments demonstrate that the Scholl reaction fails in small, unsubstituted oligophenylenes (e.g., o-terphenyl) due to oligomerization of the products (e.g., triphenylene). Incorporation of suitably placed blocking groups (e.g., t-butyl) suppresses oligomerization. The well-established directing group effects in electrophilic aromatic substitution predict the outcome of Scholl reactions of substituted substrates. Activating o,p-directing groups (e.g., MeO) direct bond formation o,p, either intramolecularly or intermolecularly. Deactivating o,p-directing groups (e.g., Br) also direct bond formation o,p but yields are lower. Deactivating m-directors (e.g., NO2) suppress reaction. MoCl5 and PhI(OOCCF3)2/BF3.Et2O are general and effective reagents for the Scholl oxidation. Calculations (B3LYP/6-31G(d)) predict the Scholl reaction in alkoxyarenes to proceed via arenium cations, not radical cations. Suzuki-Miyaura couplings were used to generate 12 substituted o-terphenyl derivatives.     

Use of functional microgels with vinyl groups to accelerate photopolymerization reaction

Three types of functional microgels with vinyl groups on their surface were prepared. For the first type, the counter anion from clorin was exchanged with β-methacryloylethyl sulfonic acid, styrene sulfonic acid or allyl sulfonic acid in a microgel with ammonium anions. For the second and third types, a quaternization with N,N-dimethylaminoethyl methacrylate of 3-chloro-2-hydroxypropyl methacrylate in the presence of microgel particles was prepared by emulsion copolymerization of styrene, chloromethylstyrene or N,N-dimethylamino-methylbenzene, and divinylbenzene. The resulting samples show good dispersibility in organic solvents without an emulsifier. A functional microgel-based photopolymer combined with an acrylate monomer and ultraviolet (UV) or visible (VIS) light-absorbing photoinitiators provides oleophilic images when exposed to UV or VIS light and developed in tap water. This photopolymer has a higher sensitivity than those of photopolymers based on microgels with an analogous composition but without vinyl groups. Photopolymers pepared by using functional microgels with a methacryloyl group exhibited a higher rate of polymerization (R_p) than that of photopolymers based on microgels without a vinyl group. The R_p of photopolymers prepared by using a functional microgel with either an allyl group or vinylphenyl group was nearly equal to that of photopolymers based on microgels with ammonium ions. Their high sensitivities are attributed to the rapid photopolymerization in the methacryloyl group. To determine how the photoreaction mechanism enhances sensitivity, the photoreaction products were investigated using a model photopolymerization system. It was found that the gelation reactions enhancing sensitivity are predominantly the polymerization and crosslinking ones when a microgel with the methacryloyl group is used, and the graft copolymerization with acrylate monomers when a microgel with either the allyl group or vinylphenyl group is used.     

Methyl groups of trimethylamine N-oxide orient away from hydrophobic interfaces

The molecular orientation of trimethylamine N-oxide (TMAO), a powerful protein stabilizer, was explored at aqueous/hydrophobic interfaces using vibrational sum frequency spectroscopy (VSFS). The systems studied included the octadecyltrichlorosilane (OTS)/water interface, which represents an aqueous solution in direct contact with a hydrophobic medium. Surprisingly, the measurements revealed that the methyl groups of TMAO pointed into the aqueous phase and away from the OTS. This orientation may arise from the more hydrophilic nature of methyl groups attached to a strongly electron-withdrawing atom such as a quaternary nitrogen. Additional studies were performed at the air/water interface. This interface showed a high degree of TMAO alignment, but the dangling OH from water was present even at 5 M TAMO. Moreover, the addition of this osmolyte modestly increased the surface tension of the interface. This meant that this species was somewhat depleted at the interface compared to the bulk solution. These findings may have implications for the stabilizing effect of TMAO on proteins. Specifically, the strong hydration required for the methyl groups as well as the oxide moiety should be responsible for the osmolyte's depletion from hydrophobic/aqueous interfaces. Such depletion effects should help stabilize proteins in their folded and native conformations on entropic grounds, although orientational effects may play an additional role.     

Synthesis of functional polyamides by the ritter reaction

Polyamides having pendant functional groups such as hydroxyl, mercapto, or imine groups were synthesized by the Ritter reaction of dinitriles and trioxane in concentrated sulfuric acid. The polymerization of β-hydroxyl glutaronitrile yielded a water-soluble polyamide having a low molecular weight which might be ascribed to the participation of the hydroxyl group with the polymerization, while the polymerization of β-mercaptoglutaronitrile resulted in the formation of a crosslinked polyamide which was insoluble in common solvents. Polymerization of dinitriles having imine groups yielded water-soluble polyamides which were effective as a coagulation agent for colloidal solutions.     

Regioselective N-alkylation of benzimidazole via an organotin route

A simple and efficient method for the exclusive N-alkylation of benzimidazole with functional group compatibility has been achieved.     

Distribution of functional groups grafted onto an ethylene-propylene copolymer

A theoretical model, based on the binomial (Bernoullian) distribution function, was employed for the prediction of functional group distribution in an ethylene-propylene copolymer randomly grafted by maleic anhydride. Using the experimentally determined graft level and molecular weight distribution function, the fraction of polymer molecules with given number of functional groups was calculated. The result was checked experimentally by a fluorescence method based on the excimer formation of pyrene fluorophores attached to the anhydride pendants. The time-resolved fluorescence from the pyrene-labeled copolymer yielded the fraction of polymer molecules with a single functional group. The fraction of singly labeled molecules was compared to the calculated functional group distribution and a reasonable agreement was found between the two. The distribution of grafted maleic anhydride was found to be apparently random among polymer molecules. The distribution of distances was calculated between randomly attached consecutive functional groups along the polymer backbone also. The result indicated that the distance distribution function (similar to a decaying exponential) is dominated by short distances. © 1996 John Wiley & Sons, Inc.     

T-for-H exchange reaction between HTO vapor and two functional groups in an aromatic compound in a gas-solid system

The hydrogen-isotope exchange reaction (T-for-H exchange reaction) between HTO vapor and an aromatic compound having two different kinds of functional groups has been observed at several temperatures. The rate constant (k) for each functional group in the T-for-H exchange reaction was obtained by using both theA″-McKay plot method and the data observed. Comparing thesek with each other has led to the following four conclusions in the T-for-H exchange reaction. (1) The reactivity of both the COOH and OH groups increases with a rise in temperature. (2) As to the degree of the effect of the COOH group on the reactivity of monosubstituted phenols, the degree inp-hydroxybenzoic acid is greater than that inm-hydroxybenzoic acid. (3) The HAMMETT rule is useful for estimating the reactivity of a certain aromatic compound. (4) TheA″-McKay plot method is also useful not only investigating the reactivity of the compounds having one kind of functional group, but also doing the reactivity of the compounds having two different kinds of functional groups.