Syntheses of vinyl polymers containing the N-phenothiazinyl group in the side chain

Four kinds of vinyl polymers containing N-substituted phenothiazinyl groups in side chains were obtained by syntheses of the respective monomers and subsequent polymerizations. Thus, N-acrylamidomethylphenothiazine, N-(N-acrylamidomethyl)carbamoylethyl phenothiazine, β-(N-phenothiazinyl)ethyl acrylate and methacrylate, and β-(N-phenothiazinyl)ethyl vinyl ether were synthesized. It was found that all monomers except the last monomer can be polymerized with typical free-radical initiators such as α,α′-azobisisobutyronitrile to afford stable soluble polymers with electron-donating characteristics, presumably due to the absence of a hydrogen atom at the site of the nitrogen atom of the phenothiazinyl group. The last monomer was found to be susceptible to typical cationic initiators such as boron trifluoride etherate to afford a stable soluble polymer also with the electron-donating characteristic.     

A Convenient Route to Functionalized Branched-Chain Sugars Via a Tosyl-Epoxide Derivative

Abstract

Starting from methyl 4,6-O-benzylidene-2-deoxy-α-D-ribo-hexopyranoside-3-ulose 1 and proceeding through its corresponding tosyl-epoxide derivative 2, various branched-chain sugars (3-8) were prepared by nucleophilic and reductive ring openings. The presence of the sulfonylated oxirane group was found to be compatible with chemical transformations of the benzylidene acetal group (9-11), allowing facile access to the 6-deoxyhexoses (12-13).     

Room-temperature polycondensation of β-amino acid derivatives VI. Synthesis of various N-(hydroxyethyl) nylons

Various N-(hydroxyethyl)amino acid esters having a methyl substituent or phenyl group between amine and ester groups have been synthesized and their polycondensation behavior was investigated. These substituted amino acid esters gave amorphous polyamides which were soluble in alcohol. A model reaction between N-(hydroxyethyl)-amine and carboxylic acid ester was carried out in order to elucidate the role of hydroxyethyl group on the polycondensation. It was found that the amidation reaction took place rapidly at room temperature when the alkyl group of the carboxylic acid was small. N-(Hydroxyethyl) polyamides were obtained from N,N′-(bishydroxyethyl)-dicamines and dicarboxylic acid esters. The reaction mechanism of the room-temperature polycondensation reaction is discussed.     

1H NMR studies of intramolecular hydrogen bonding in N-(pyridyl)amides of 6-methylpicolinic acid N-oxide

The ¹H NMR spectra of seven N-(pyridyl)amides of 6-methylpicolinic acid N-oxide in chloroform were obtained. The influence on the chemical shifts of the N? H protons of temperature, concentration and the CH₃ substituent in the pyridine ring was studied. The N? H protons were found to be shifted to low fields (～14 ppm) owing to the formation of strong intramolecular hydrogen bonding. The influence of the pyridine ring on the chemical shift of the N? H proton is comparable with the inductive effect of the p-nitrophenyl group. The hindered rotation around the N-pyridyl bond of N-(α-pyridyl)amides of 6-methylpicolinic acid in solution is discussed.     

Alkyl Ether Analogs of Chlorophyll-a Derivatives: Part 1. Synthesis, Photophysical Properties and Photodynamic Efficacy

The synthesis, preliminary in vivo biological activity, singlet oxygen and fluorescence yields of a series of alkyl ether derivatives of chlorophyll-a analogs are described. For short-chain carbon ethers (1–7carbon units), it was observed that the biological activity increased by increasing the length of the carbon chain, being maximum in compounds with n-hexyl and n-heptyl chains. Related sensitizers prepared by reacting 2-(1-bromoethyl)-2-devinylpyropheophorbide-a with (sec)alcohols were found to be less effective. Under similar treatment conditions, photosensitizers containing cis- and trans- 3-hexenyl side chains were ineffective. Thus, both stereochemical and steric factors caused differences in sensitizing activity. In general, pyropheophorbide-a analogs were found to be more active than related chlorin e₆ derivatives, in which the isocyclic ring (ring “E”) was cleaved. Related photosensitizers in the 9-deoxy- series were found to be as effective as the corresponding pyropheophorbide-a analogs. The photosensitizers prepared from pyropheophorbide-a methyl ester and chlorin e₆ trimethyl ester have long wavelength absorption at 660 nm (ε 45000 to 50000). Reduction of the carbonyl group in the pyropheophorbide-a to methylene (ring E) resulted in a blue shift to 648 nm (ε 38000).     

Mass spectrometry of N-(Pyrimidin-2-yl)amino acids and their methyl esters

N(Pyrimidin-2-yl)-glycine, -alanine and -phenylalanine (1-3) and their methyl esters (4-6) were investigated using electron impact (EI) mass Spectrometry. The results showed that EI-induced decomposition occurs on the carboxylic group or involves the loss of R₂OH. In contrast to earlier investigations on N-(pyrimidin-4-yl)amino acids, elimination of water (in 1-3) or methanol (in 4-6) was found to be of EI-induced nature. The loss of 'COOH from M⁺ of ester 4 suggests the occurrence of a skeletal rearrangement leading to the isomeric N-methylamino acid.     

Photo-oxidation of the 2,4-dichloropentanes and PVC

The photo-oxidation of PVC and its model compounds, the dl- and meso-2,4-dichloropentanes, were studied by high-resolution NMR spectroscopy. The structure, ? CHCl? CH₂? CO? CH₂? was found to be present in PVC after photo-oxidation. Two peaks, which corresponded to the CHCl and CH₂ groups next to the carbonyl group, were observed in carbon disulfide–acetone-d₅ mixture, at 6.15 and 7.25τ, respectively. From the NMR spectra, the ratio of the CH₂ to CHCl protons in PVC and the model compounds were found to increase linearly with the time of photo-oxidation after induction periods. The initial rates of the model compounds were comparable with that of PVC; i.e., 1.6 × 10^?2 hr^?1, at 30°C. Since similar gaseous products were also detected by mass spectrometry in the initial stage, their photo-oxidation probably assumed the same rate-determining step. According to the results that the dl-2,4-dichloropentane was photo-oxidized 1.5 times faster than the meso-compound, it would be likely that the syndiotactic sequences in PVC might be more easily photo-oxidized than the isotactic sequences.     

Synthesis of antimicrobial agents. II. Syntheses and antibacterial activities of optically active 7-(3-hydroxypyrrolidin-1-yl)quinolones

Two optically active isomers of 1-ethyl-6,8-difluoro-1,4-dihydro-7-(3-hydroxypyrrolidin-1-yl)-4-oxoquinoline-3-carboxylic acid ( 10 ) were prepared. One of the isomer, 7-[(3S)-hydroxypyrrolidin-1-yl] derivative 8 , was about 4 times more potent in vitro than the other, 7-[(3R)-hydroxypyrrolidin-1-yl] derivative 4 , and approximately two times more active than the racemate, 7-[(3RS)-hydroxypyrrolidine-1-yl] derivative 10. Optical active 8 was the most active in in vivo, followed by 10 , and 4 was the least active compound. But, they were more potent than CI-934 12 and norfloxacin. From the results, (3S)-hydroxypyrrolidinyl group was found to be one of the beneficial group for PCA-anti-bacterial agent.     

Die Aminoalkylierung von Carbonylverbindungen mit Hilfe der Wittig-Reaktion

The Aminoalkylation of Carbonyl Compounds by the Wittig-Reaction The Wittig reaction would be a very suitable way to replace the carbonyl group in aldehydes and ketones by a 2-amino-ethylidene group if a simple and convenient method could be devised for synthesizing (2-amino-ethyl)triphenylphosphonium bromides 3 . We have synthesized compounds of type like (2-dialkylaminoethyl)-, (2-morpholino-ethyl)-, (2-(1-imidazolyl)ethyl)-, and (2-(1-triazolyl)ethyl)-triphenylphosphonium bromides (cf. Table 1), by melting at 150° the hydrobromides of triphenylphosphine and of the appropriate 2-amino-ethanol. The phosphonium bromides of type 3 could be converted with ketones by the Wittig reaction into the desired amino-ethylidene compounds of type 2 , e.g. 18 – 22 (Table 2). In the case of the reaction with 4-chlorobenzaldehyde the steric course of the transformation was studied, and conditions were found favoring either cis or trans compounds (e.g. 27a or 27b in the reaction of the phosphonium bromide 11 , cf. Table 3).     

Fast and Reliable Automated Synthesis of RNA and Partially 2′-O- Protected Precursors (`Caged RNA') Based on Two Novel,Orthogonal 2′-O-Protecting Groups,Preliminary Communication

Two sets of RNA phosphoramidites, carrying the (fluoride-labile) 2′-O-[(triisopropylsilyl)oxy]methyl (=tom) group and the (photolabile) [(R)-1-(2-nitrophenyl)ethoxy]methyl (=(R)-npeom) group, were prepared (see 1 – 4 and 5 – 8 , resp.). The two protecting groups were completely orthogonal to each other. Three ribozyme-substrate constructs, protected each by a (R)-npeom group, were synthesized; on photolysis, efficient cleavage of this remaining protecting group occurred (Scheme 3). It could be demonstrated that the presence of one (R)-npeom group within a RNA strand has only a minor influence on the pairing properties of corresponding duplexes.     

Solution equilibria of aromatic dinitroso compounds: a combined NMR and DFT study

Solution-state nitroso monomer-azodioxide equilibria and conformational freedom of several aromatic dinitroso derivatives, differing in the spacer group between the aromatic rings, were studied by one- and two-dimensional variable temperature ¹H NMR spectroscopy and by quantum chemical calculations. The proton signals of nitroso monomer-azodioxide mixtures revealed by low-temperature NMR were assigned and validated using B3LYP-D3/6-311+G(2d,p)/SMD level of theory. In almost all cases, a preference towards the formation of only one azodioxy isomer of aromatic dinitroso compounds was found, which was assigned to Z-dimer according to computational data. Nevertheless, the computed small energy difference between the Z- and E-isomer could not account for the extreme preference for Z-dimer formation, indicating an influence of entropic or solvent effects. The formation of shorter oligomers in solution was excluded based on integrated ¹H NMR signal intensities. The experimental results indicated an average dimerization Gibbs energy of about ??5 kJ/mol at 223 K and were found to be in very good correlation with dimerization energies obtained by solution-phase optimization.

     

Design,synthesis, and anticancer activity evaluation of novel aziridine-1,2,3-triazole hybrid derivatives

Some new 1-aryl-4-[(aziridine-1-yl)diaryl-methyl]-5-methyl-1H-1,2,3-triazole derivatives 7j–s were synthesized by the one-pot reaction of diaryl-(1-aryl-5-methyl-1H-1,2,3-triazol-4-yl)methanol compounds 6j–s formed from 1-aryl-5-methyl-1H-1,2,3-triazole-4-carboxylic acid derivatives. The new compounds 7j–s and 6j–s are investigated by ¹H and ¹³C NMR, MS, and IR. The anticancer activity of the synthesis target compounds was evaluated against human leukemia (HL-60) cells and human hepatoma G2 cells. Some of the compounds were highly efficient. The ¹H-NMR signals of the aziridine-ring cis-H/trans-H protons were found to be two group peaks at 1.800–1.884 and 1.183–1.327?ppm.     

Oxidation of menthone oxothiolane

meta-Chloroperoxybenzoic acid (m-ClPBA) was shown to be an oxidant for two stereoisomers of menthone oxothiolane. The effect of steric factors on the ability to oxidize the sulfide group was found. Oxidation of (5S,6S,9R)-6-isopropyl-9-methyl-1-oxo-4-thiaspiro[4.5]-decane to the sulfone was prevented by the steric proximity of an isopropyl group to the S atom in the oxothiolane ring. Translated from Khimiya Prirodnykh Soedinenii, No. 6, pp. 588–590, November–December, 2008.     

Conformational analysis of N-arachidonylethanolamide (anandamide) using nuclear magnetic resonance and theoretical calculations

The conformational properties of cis-5,8,11,14-eicosatetraenoylethanolamide (anandamide) were analysed by the combined use of NMR experimental results plus molecular simulations. The structure of anandamide was found to be a predominantly linear with a seven-atom ring of the ethanolamine group having a hydrogen bond which stabilizes the molecule. The vinylic group present has a cis conformation in solution. The terminal chain has a linear conformation and undergoes isotropic fast motion typical of this structure. Copyright © 2001 John Wiley & Sons, Ltd.     

Mass spectrometry in structural and stereochemical problems—CXCIX Contrasting fragmentations of singly- and doubly-charged o-, m- and p-hydroxyalkylphenones and their trimethylsilyl ethers

High resolution mass spectrometry, metastable defocusing and deuterium labeling of trimethylsilyl (TMS) ethers have been used to study the electron-impact induced fragmentations of o-, m- and p-hydroxyalkylphenones and their TMS ether derivatives. These derivatives have proven useful in contrasting the fragmentation patterns of singly- and doubly-charged ions because of the competing fragmentations: α-cleavage and a McLafferty rearrangement from the ketone moiety and methyl cleavage from the TMS group. A proximity effect was responsible for a markedly increased methyl radical loss from the o-TMS ether. This fragmentation was minor with the m- and p-isomers. Significantly intense doubly-charged ions were formed from ketonic cleavage and by the loss of a TMS methyl radical. The sequence of fragmentation depended on the size of the alkyl group attached to the ketone carbonyl. There was no evidence found for a McLafferty rearrangement occurring from the doubly-charged molecular ion of the TMS ethers of the hydroxyalkylphenones but the rearrangement occurred from the doubly-charge molecular ion of bis-3-(1-oxopentyl)-4-hydroxy-phenyl-methane and, of course, from the singly charged [M]^+. The bis-p-hydroxyphenylmethane derivatives were studied in an effort to increase the intensity of the doubly-charged ions as it was expected that the charges would be separated by a longer distance.     

Electron spin resonance spectrum of the diphenylcyclobutene anion radical

The anion radical of 1,2-diphenylcyclobutene was studied by electron spin resonance. The hyperfine splittings were found to be 0·47 and 0·74 G for the meta-positions, 2·23 and 2·69 G for the ortho-positions and 4·21 G for the para-positions of the phenyl rings. The methylene proton splittings were 4·27 G, which would imply that the value of Q is 27 G, much lower than that of other cyclobutene anions. It was also estimated that the angle between the axis of the p-orbitals of the ethylene group and that of the phenyl group is about 30°, in agreement with that found for the tetraphenylethylene anion.     

Potential antipsychotic agents. Part 8. Antidopaminergic properties of a potent series of 5-substituted (−)-(S)-N-[(1-ethylpyrrolidin-2-yl)methyl]-2,3-dimethoxybcnzaimides. Synthesis via common lithio intermediates

A series of 5-substituted (?)-(S)-N-[(1-ethylpyrrolidin-2-yl)methyl]-2,3-diniethoxybenzanndes were made by reaction of the corresponding benzoyl chlorides with (S)-1-ethylpyrrolidine-2-methylaruine (→ 14–16 , 18–21 ). The acids required were prepared in a regiospecific manner from 5-bromo-2,3-dimethoxybenzoic acid which was protected as dihydrooxazole (→ 4–8 ), metalated, reacted with various electrophiles (MeI, EtI, BuBr, CC1³CCl³ or MeSSMe), and hydrolyzed (→ 9–13 ). Alternatively, (-)-(S)-5-bromo-N-[(1-ethylpyrrolidin-2-yl)methyl]-2,3-di-methoxybenzamide was treated with KH followed by BuLi and an electrophile (I₂ or Me³SiCl) to give the 5-iodo and 5-(trimethylsilyl) derivatives 17 and 22 , respectively. All 5-substituted amides were highly potent inhibitors of [³H]spiperone binding in rat striatal membranes with IC⁵⁰ values of 0.5 to 5 nM (Table 3). Thus, a relatively large steric bulk can be accomodated in the position para to the 2-MeO group. This work also supports the notion that a positive as well as negative electrostatic potential can be located in this position. A selected number of derivatives were also investigated in vivo and found to inhibit apomorphine-induced behavioural responses in the same dose range as haloperidol and raclopride (Table 4). This new group of benzamides is suitable for investigations of dopamine D-2 receptors in labelled or unlabelled form.     

Preparation and characterization of organosoluble copolyimides based on a pair of commercial aromatic dianhydride and one aromatic diamine, 1,2-bis(4-aminophenoxy)-4-tert-butylbenzene, series

 A series of copolyimides with high molecular weights, excellent mechanical properties, heat-resistant properties, and good solubilities in organic solvents were synthesized from six kinds of commercial dianhydrides and 1,2-bis(4-aminophenoxy)-4-tert-butylbenzene. Monomers for synthesizing insoluble polyimides and monomers for synthesizing soluble polyimides were used to synthesize semialternating copolyimides with arbitrary solubilities. Fifteen kinds of soluble copolyimides were synthesized through chemical or thermal cyclodehydration. These copolyimides were found to be easily soluble as well as able to be processed by casting from solutions such as N-methyl-2- pyrrolidone, N,N-dimethylacetamide, dimethylformamide, dimethyl sulfoxide, m-cresol, and tetrahydrofuran. The easily dissolved characteristics of this series of copolyimides stemmed from the tert-butyl group, the ortho-linked aromatic unit, and the ether group within 4-tert-butylbenzene. Besides, when the dianhydride molecules used contained organosoluble groups and were mixed at varying molar ratios, the solubilities in organic solvents could be greatly enhanced. The copolyimides could improve the processability of polymers, while maintaining or increasing their excellent mechanical properties and heat-resistant properties. Received: 21 July 2000 Accepted: 13 December 2000     

Cyclization Studies with N-Mannich bases of 2-substituted indoles

The synthesis of the indoles 7 , 15 , 16 with a 3-methoxyphenyl group, attached via an α-side chain of 1,2,or 3 CH₂ units, is reported. These compounds, after appropriate protection at C(3), were transformed into the N-[(dimethylamino)methyl]indoles 22 , 23 , and 24 , respectively. When treated with AcCl, these N-Mannich bases gave, in two cases, stable N-(chloromethyl)indoles 25 and 26 . In the presence of SnCl₄, ring closure occurred via electrophilic attack of 1-methylideneindolium ions on the methoxyphenyl group. Formation of seven-membered rings (→ 27 , 28 ) and eight-membered rings (→ 29 ) was found to be a favorable process. Cyclization to six-membered rings did not occur within this series.     

NMR study of 2-alkoxy-1,3,2-dioxaphospholanes. II—molecular conformation of alkoxy substituents

The conformation of some 2-σ-1,3,2-dioxaphospholanes (σ=OAlkyl, CI) is studied. The determination of the ²J(POC) and ³J(POCC) coupling constants, which are influenced by the bulk of the alkoxy group, is a means of obtaining information about the rotation around the P? OR bond, which is dependent on steric interactions between the phosphorus lone pair, the alkoxy group and the substituents on the ring. When σ is a tert-butoxy group, a direct ‘through-space’ interaction is found between the phosphorus atom and one of the primary carbons of the OR group. If there is no substituent on the ring, the ³¹P chemical shifts are little affected by changes in OR; a diamagnetic effect is observed, however, in the case of the tert-butoxy group which is enhanced for the 4,4,5,5-tetramethyl derivatives.