Base-Catalyzed Polymerization of Vinyl Acetamide and Allyl Cyanide

The base-catalyzed polymerizations of vinyl acetamide and allyl cyanide have been studied. It was found by chemical and spectroscopic analyses that the polymer obtained from vinyl acetamide was poly(2-methyl-β-alanine), which was the same structure as the polymer prepared by base-catalyzed polymerization of crotonamide. It is concluded, therefore, that vinyl acetamide was polymerized through the isomerization of allyl group and the proton transfer reaction from amide group. The gas-chromatographic analysis of the polymerization system showed that vinyl acetamide was consumed faster than crotonamide. This, fact suggests that an intermediate other than crotonamide might be present in the process of isomerization of vinyl acetamide. On the other hand, in the base-catalyzed polymerization of allyl cyanide, the allyl group was isomerized, but the reaction of cyanide group hardly occurred.     

Synthesis of 4-substituted glutarimides by free radical addition of iodoacetamide to α,β-unsaturated esters

Free radical addition of either methyl bromoacetate or iodoacetamide to an α,β,-unsaturated ester gave the 4-substituted glutarate or glutarimide respectively, whereas the radical cyclisation of N-bromoacetyl crotonamide gave the 2-substituted succinimide.     

Zur wecheslwirkung der amidfunktion mit dem β-C-atom bei zerfällen α,β-ungesättigter amid: Sauerstoff- odder stickstoff-attacke?

Investigation of ¹³C labelled crotonamide and analysis of the collisional activation spectra from sutitable reference compounds have shown that the radical elimination from the β-C-atom, caused by a neighbouring group interaction between the β-C-atom and the amide function, is essentially induced by a nitrogen attack and only to a minor extent by an attack of the carbonyl oxygen upon the β-C-atom. The resulting ion strucstures are discussed.     

Derivatives of (2R)-N-Glyoxylbornane-10,2-sultam and Their Use as auxiliaries in the diastereoselective spirocyclization of 2-substituted tryptamines

A crude hydrate 6 and a crystalline hemiacetal 7 of glyoxylamide 4 were prepared from crotonamide 5 (Scheme 2). Particularly hemiacetal 7 , but also 6 and the ‘dimer’ 8 (obtained from 7 ) may serve as homochiral auxiliaries. The structure of 8 was determined by X-ray analysis. By arenesulfonyl halides, tryptimines 12–14 of 4 were diastereoselectively transformed into spirotricycles 15–17 and 19 .     

1,6-Asymmetric induction during the conjugate addition of arylcopper reagents to a chiral sulfinyl-substituted pyrrolyl alpha,beta-unsaturated amide.

The asymmetric conjugate addition of arylcopper reagents derived from aryl Grignard reagents and copper(I) iodide to a chiral 1-[2-(p-tolylsulfinyl)]pyrrolyl cinnamide proceeded smoothly to give (3R)-adducts with high diastereoselectivities (> or =92% de) in high yields. Conjugate additions either of the cinnamide with the alkyl Grignard reagent-copper(l) iodide combination or of the crotonamide derivative with aryl Grignard reagent-copper(l) iodide gave moderate to good diastereoselectivities. With these sulfinyl pyrrolyl alpha,beta-unsaturated amides, the chiral auxiliary was efficiently recovered without any loss of optical purity after asymmetric conjugate addition.     

Rhodium(I)-catalyzed asymmetric 1,4-addition of arylboronic acids to alpha,beta-unsaturated amides.

The conjugate addition of arylboronic acids to alpha,beta-unsaturated amides was carried out in the presence of a chiral rhodium catalyst and an aqueous base. The catalyst prepared in situ from Rh(acac)(CH(2)=CH(2))(2) and (S)-binap provided (R)-N-benzyl-3-phenylbutanamide with 93% ee in the addition of phenylboronic acid to N-benzyl crotonamide. The reaction suffered from incomplete conversion resulting in moderate yields, but addition of an aqueous base, such as K(2)CO(3) (10-50 mol%) was found to be highly effective to improve the chemical yields. The role of the base giving a RhOH species active for transmetalation with arylboronic acids was discussed.     

Synthesis of versatile chiral intermediates by enantioselective conjugate addition of alkenyl Grignard reagents to enamides deriving from (R)-(−)- or (S)-(+)-2-aminobutan-1-ol

Conjugate addition of but-3-enylmagnesium bromide to the chiral crotonamide (R)-(+)- and (S)-(−)-3, followed by hydrolysis and oxidation, afforded enantiopure (R)-(+)- and (S)-(−)-3-methyladipic acids 8, respectively. Conjugate addition of vinylmagnesium chloride to the chiral crotonamide and cinnamamides (R)-(+)-3–5, followed by hydrolysis, gave the alkenoic acids (S)-12–14, respectively. Iodolactonization of the latter led to the 5-iodomethyllactones (+)-15–17, which were reduced by means of n-Bu₃SnH into the trans-disubstituted 5-methyllactones (+)-19–21, respectively. Treatment of the iodomethyllactone (+)-16 with LiMe₂Cu or n-Bu₂CuLi furnished the trans-5-alkyl-4-phenyllactones (−)-22 or (+)-23.     

1,3‐Dipolar Cycloaddition Reaction of Nitrile Oxides Revisited—Unusual Side Products Characterized by 2D NMR

Cycloaddition of (4‐trifluoromethyl)phenylnitrile oxide to N‐(4‐methoxyphenyl)acrylamide afforded bicyclic tetrahydro‐oxazolo‐(3,2‐b)[1,3]oxazine‐2‐carboxamide derivative in result of N‐acylation of the initially formed cycloadduct by the dipolarophile. 2:1 Cycloaddition of the same dipole to N‐(4‐methoxyphenyl)crotonamide yielded dihydro[1,2]‐oxazolo[2,3‐d][1,2,4]oxadiazole‐7‐carboxamide because of the second addition of the dipole to the C═N bond of the first formed 2‐isoxazoline compound. Structures of the products have been elucidated by an extensive application of 1D and 2D NMR spectroscopy.     

On the reactions between ethyl benzoylacetate and anisidines

4-Hydroxy-7-methoxy-3-[(m-methoxyphenylimino)-phenylmethyl]-2-quinolone ( 6 ) was a by-product of the condensation of ethyl benzoylacetate and m-anisidine; no corresponding products were obtained from p- and o-anisidine. From o-anisidine, 2-phenyl-8-methoxy-4-quinolone ( 1c ) was isolated and characterized; the same reaction also gave 2-phenyl-4-o-anisidyl-1-8-methoxy-quinoline ( 11 ) and the Schiff base ( 14 ) as by-products; the crotonamide (15) also isolated, is a possible intermediate of the cyclization. The direct condensation of anisidines with ethyl benzoylacetate in diphenyl ether and the transformations of some intermediates were studied.     

Synthesis and molecular structure of piplartine (=piperlongumine)

The structure of piplartine (=piperlongumine) was established as ($\text{1}$)-$\text{3}$-3',4',5'-trimethoxycinnamoyl-5,6-dihydro-2(1H)-pyridone ($\text{13}$) by synthesis and by an X-ray crystallographic analysis. Model condensation of ($\text{E}$)-3,4,5-trimethoxycinnamoyl chloride and crotonamide gave not the expected cinnamoylcrotonamide, but ($\text{1}$)-$\text{N}$-3', 4', 5' -trimethoxycinnamoyl-3-chlorobutyramide ($\text{12}$).     

Synthesis and Chemical Conversions of 2-Chloro-3-cyano-4-methylamino-5-nitropyridine

5-Cyano-6-(-dimethylamino)vinyl-1-methyl-4-pyrimidinone was synthesized by the interaction of -cyano--(N-methylamino)crotonamide with N,N-dimethylformamide diethylacetal. Recyclization of the product in alkaline medium leads to 3-cyano-4-methylamino-2-pyridone. Nitration of the latter and transformation of the nitropyridone by boiling in POCl₃ gave 2-chloro-3-cyano-4-methylamino-5-nitropyridine. This is a key compound for various transformations including the synthesis of derivatives of dipyrido[1,2-a:3,2-e]pyrimidine, thieno[2,3-b]pyridine, and (2-pyridylamino)polyene derivatives.     

Hydrogen-transfer polymerization of methyl-substituted acrylamides

Base-catalyzed hydrogen-transfer polymerization and copolymerization of acrylamide and its methyl-substituted derivatives were studied in pyridine at 110°C. n-Butyllithium was used as an initiator. The observed rates of these homopolymerizations were found to decrease in the following order: acrylamide > crotonamide > methacrylamide > N-methylacrylamide > N-methylcrotonamide > tiglinamide > N-methylmethacrylamide ? α-chlorocrotonamide ? α-cyanocrotonamide = 0. Acrylamide gave the polymer with the highest degree of polymerization among the monomers examined. It was found that the number and the position of the methyl substituent in acrylamide affected significantly both the rate of polymerization and the molecular weight of the polymer. Although all polymers obtained, except the N-methyl derivatives, contained both methanol-soluble and methanol-insoluble fractions, a polyamide structure with unsaturated terminal monomer unit was confirmed by both infrared and NMR determinations. From the NMR determination of the saturated and terminal unsaturated units, the degree of polymerization of the resulting polyamides were also obtained. The monomers were also found to copolymerize by a hydrogen-transfer mechanism. However, the main chain of the resulting copolymers was composed of the more reactive monomer unit, and the less reactive monomer was incorporated only as a terminal unit when a less reactive monomer was copolymerized with a more reactive one. From these results, it was concluded that these polymerizations proceeded via an intermolecular hydrogen-transfer mechanism (i.e., stepwise mechanism).     

Sixteen capillary electrophoresis applications for viral vaccine analysis

A broad range of CE applications from our organization is reviewed to give a flavor of the use of CE within the field of vaccine analyses. Applicability of CE for viral vaccine characterization, and release and stability testing of seasonal influenza virosomal vaccines, universal subunit influenza vaccines, Sabin inactivated polio vaccines (sIPV), and adenovirus vector vaccines were demonstrated. Diverse CZE, CE-SDS, CGE, and cIEF methods were developed, validated, and applied for virus, protein, posttranslational modifications, DNA, and excipient concentration determinations, as well as for the integrity and composition verifications, and identity testing (e.g., CZE for intact virus particles, CE-SDS application for hemagglutinin quantification and influenza strain identification, chloride or bromide determination in process samples). Results were supported by other methods such as RP-HPLC, dynamic light scattering (DLS), and zeta potential measurements. Overall, 16 CE methods are presented that were developed and applied, comprising six adenovirus methods, five viral protein methods, and methods for antibodies determination of glycans, host cell-DNA, excipient chloride, and process impurity bromide. These methods were applied to support in-process control, release, stability, process- and product characterization and development, and critical reagent testing. Thirteen methods were validated. Intact virus particles were analyzed at concentrations as low as 0.8 pmol/L. Overall, CE took viral vaccine testing beyond what was previously possible, improved process and product understanding, and, in total, safety, efficacy, and quality.     

Spectrophotometric and fluorimetric determination of diazepam, bromazepam and clonazepam in pharmaceutical and urine samples

New spectrophotometric and fluorimetric methods have been developed to determine diazepam, bromazepam and clonazepam (1,4-benzodiazepines) in pure forms, pharmaceutical preparations and biological fluid. The new methods are based on measuring absorption or emission spectra in methanolic potassium hydroxide solution. Fluorimetric methods have proved selective with low detection limits, whereas photometric methods showed relatively high detection limits. Successive applications of developed methods for drugs determination in pharmaceutical preparations and urine samples were performed. Photometric methods gave linear calibration graphs in the ranges of 2.85-28.5, 0.316-3.16, and 0.316-3.16 microgml-1 with detection limits of 1.27, 0.08 and 0.13 microgml-1 for diazepam, bromazepam and clonazepam, respectively. Corresponding average errors of 2.60, 5.26 and 3.93 and relative standard deviations (R.S.D.s) of 2.79, 2.12 and 2.83, respectively, were obtained. Fluorimetric methods gave linear calibration graphs in the ranges of 0.03-0.34, 0.03-0.32 and 0.03-0.38 microgml-1 with detection limits of 7.13, 5.67 and 16.47 ngml-1 for diazepam, bromazepam and clonazepam, respectively. Corresponding average errors of 0.29, 4.33 and 5.42 and R.S.D.s of 1.27, 1.96 and 1.14 were obtained, respectively. Statistical Students t-test and F-test have been used and satisfactory results were obtained.     

Effect of certain chemical compounds on secondary metabolites of Penicillium janthinellum and P. duclauxii

The secondary metabolites of Penicillium janthinellum and P. duclauxii were affected by different concentrations of cadmium nitrate, sodium chloride, and sucrose. The fungal culture characteristics including mycelial fresh and dry weight, colony diameter, colony spore mass and reverse color, number of spores, and secondary metabolites were affected as well. Cyclopenin, carlosic acid, erythroskyrin, kojic acid, and patulin were produced by P. janthinellum on cadmium nitrate-free medium. However, cyclopenin, carlosic acid, frequentin, and islandicin were produced at 100 ppm, and cyclopenin at 500 ppm. On the other hand, the secondary metabolites produced by P. duclauxii were 9 on cadmium nitrate-free medium, 7 on medium containing 100 and 500 ppm of cadmium nitrate, and 4 at 1000 ppm cadmium nitrate concentration. Secondary metabolite brevianamide A was produced in the presence and absence of cadmium nitrate. The duclauxin, patulin, terrestic acid, and xanthomegin were produced only on cadmium nitrate-free medium. However, mycophenolic acid was produced only on cadmium nitrate-containing medium. The kojic acid was produced by P. janthinellum at 0.0%, 0.5%, 1.0%, 2.0%, 3.0%, and 5.0% concentrations of sodium chloride. The carlosic acid, erythroskyrin, and patulin were produced only at 0.0% and 1.0%. While carolic acid and islandicin were produced at 1%, 2%, and 3% and frequentin was produced only at 2% and 3%. On the other hand, 8 secondary metabolites were produced by P. duclauxii at 0.0%, 0.5%, 1.0%, and 2.0% concentration of sodium chloride and only 4 were produced at 3%. The secondary metabolites produced by P. janthinellum were 7 at 10% and 20%, 6 at 30%, and 2 only at 40% concentrations of sucrose. However, 8 secondary metabolites were produced by P. duclauxii at 10%, 20%, 30% and 3 at 40% concentrations of sucrose.     

The Book Corner

Abstract

Liquid Chromatography/Mass Spectrometry, Techniques and Applications, A. L. Yergey, C. G. Edmonds, I. A. S. Lewis, and M. L. Vestal, Modern Analytical Chemistry Series, D. Hercules, Editor, 306 pages, Plenum Press, New York and London, 1989. $65.00; price 20% higher outside USA and Canada.

Analytical Microbiology Methods, Chromatography and Mass Spectrometry, A. Fox, S. L. Morgan, L. Larsson and G. Odham, Editors, Plenum Press, New York and London, 1920, 280 pages. $65.00; prices 20% higher outside USA and Canada.

Ion Chromatography, H. Small, Modern Analytical Chemistry Series, D. Hercules, Editor, Plenum Press, New York and London, 1990, 376 pages. $49.50; prices 20% higher outside USA and Canada.     

3D printing to innovate biopolymer materials for demanding applications: A review

Biopolymers are widely available, low-/nontoxic, biodegradable, biocompatible, chemically versatile, and inherently functional, making them highly potential for a broad range of applications such as biomedicine, food, textile, and cosmetics. 3D printing (3DP) is capable of fabricating some customized, complex material structures composed of single or multiple material constituents that cannot be achieved by conventional methodologies (e.g. internal structures design); thus, 3DP can greatly expand the application of biopolymer materials. This review presents a comprehensive survey of the latest literature in 3DP technology for materials from biopolymers such as polysaccharides and proteins. The most commonly used 3DP techniques (i.e. inkjet printing, extrusion-based printing, stereolithography, selective laser sintering, and binder jetting) in biomedical and food fields are discussed. Critical factors affecting the quality and accuracy of 3D-printed constructs, including rheological characteristics, printing parameters (e.g. printing rate, and nozzle diameter, movement rate, and height), and post-printing processes (e.g. baking, drying, and crosslinking) are analyzed. The properties and the emerging applications of 3D-printed biopolymer materials in biomedical, food, and even wider applications (e.g. wastewater treatment and sensing) are summarized and evaluated. Finally, challenges and future perspectives are discussed. This review can provide insights into the development of new biopolymer-based inks and new biopolymer-based 3D-printed materials with enhanced properties and functionality.     

Determination of carbamazepine and its impurities iminostilbene and iminodibenzyl in solid dosage form by column high-performance liquid chromatography

An accurate and precise RP-HPLC method was developed and validated for the determination of carbamazepine and its impurities iminostilbene and iminodibenzyl in a tablet formulation with fluphenazine as an internal standard. Buffer-methanol (50 + 50, v/v) was used as the mobile phase. During validation, specificity, linearity, precision, accuracy, LOD, LOQ, and robustness of the method were tested. The method was proven to be specific against placebo interference. Linearity was evaluated over the concentration range of 100-500, 0.05-0.25, and 0.1-0.5 microg/mL, and the r values were 0.9994, 0.9997, and 0.9979 for carbamazepine, iminostilbene, and iminodibenzyl, respectively. Intraday precision of the method was good, and RSD was below 2% for all analytes. The accuracy of the method ranged from 100.69 to 102.10, 99.76 to 102.66, and 99.26 to 100.08% for carbamazepine, iminostilbene, and iminodibenzyl, respectively. LOD was 0.0125, 0.025, and 0.05 microg/mL and LOQ was 0.05, 0.05, and 0.1 microg/mL for carbamazepine, iminostilbene, and iminodibenzyl, respectiviely. Robustness of the method was proven by using a chemometric approach. The method was successfully applied to the analysis of commercially available carbamazepine tablets and showed good repeatability, with RSD below 2%.     

Stress-induced increase in the amounts of maysin and maysin derivatives in world premium natural compounds from centipedegrass

The red leaves of centipedegrass are known to produce compounds with stronger antibiotic effects than those produced by green leaves. Therefore, the aim of this study was to identify if stress methods (e.g., gamma irradiation, UV-B irradiation, and wounding) could effectively convert green leaves to red leaves, and thereby increase the production of maysin and maysin derivatives that have been known for antibiotic properties. Our results showed differential concentration changes for different compounds using these stress methods. The concentrations of luteolin increased from 0.014% to 0.019%, 0.022%, and 0.028% following gamma irradiation, UV-B irradiation, and wounding, respectively. The concentration of isoorientin increased from 0.898% to 1.938% and 2.538%, while the concentration of mixed rhamnosylisoorientin and orientin increased from 0.303% to 0.474% and 0.690%, following UV-B irradiation and wounding, respectively. Gamma irradiation produced concentrations of isoorientin, rhamnosylisoorientin, and orientin similar to those found in red leaves. The concentrations of derhamnosylmaysin increased from 0.004% to 0.009%, 0.015%, and 0.024% by gamma irradiation, UV-B irradiation, and wounding, respectively. The concentration of maysin increased from 0.515% to 0.714%, 0.583%, and 0.777% by gamma irradiation, UV-B irradiation, and wounding, respectively, while the concentration of luteolin-6-C-boivinopyranoside increased from 0.324% to 0.834%, 0.979%, and 1.493% by gamma irradiation, UV-B irradiation, and wounding, respectively. According to these results, wounding and gamma irradiation are promising methods for increasing the concentrations of maysin and maysin derivatives.