Lithium-Salt Effects in Peptide Synthesis. Part I. Conditions for the Use of Lithium-Salts in Coupling Reactions

The influence of Li-salts on the course of peptide-coupling reactions was investigated. As a model for segment couplings, Ac-Phe-OH was coupled to HCl·H-Ala-OMe using the mixed anhydride, DCC1, DCCl/HOBt, BOP-Castro and TBTU-Knorr methods. As a model for stepwise synthesis Z-Phe-OH was coupled with HCl·Ala-O(t-Bu), using symmetrical anhydrides and active esters. The effects of salt additives such as LiCl, LiBr, LiC10₄, and ZnCl₂ on yields, side-product formation, racemisation, and reaction rates are reported.     

A Tripeptide Approach to the Solid-Phase Synthesis of Peptide Thioacids and N-Glycopeptides

A general and robust method for the incorporation of aspartates with a thioacid side chain into peptides has been developed. Pseudoproline tripeptides served as building blocks for the efficient fluorenylmethyloxycarbonyl (Fmoc) solid-phase synthesis of thioacid-containing peptides. These peptides were readily converted to complex N-glycopeptides by using a fast and chemoselective one-pot deprotection/ligation procedure. Furthermore, a novel side reaction that can lead to site-selective peptide cleavage using thioacids (CUT) was discovered and studied in detail.     

Synthesis of phenylpyrrolylpyrroles. Part II

A series of methyl or ethyl 3-(N-arylpyrrol-3-yl)-1H-pyrrole-2-carboxylates and 2,4-dicarboxylates have been synthesized using an alkyl isocyanides addition-cyclization with N-arylpyrrole derivatives such as the carboxaldehydes and nitropropenes.     

Side Reactions in Peptide Synthesis: Failure of Coupling in Solid-Phase Automatic Synthesis of a Fragment (Sequence 65-74) of the Acyl Carrier Protein

Two major side-products and a desired peptide (each was one-third) were found in analysis of a synthesized fragment (65-74) of the acyl carrier protein by a solid-phase automatic peptide synthesizer. The peptide mixtures were separated and collected by HPLC. Each isolated peptide was characterized via amino-acid composition analysis, mass spectra and specific peptide-bond cleavage to prove the sequence. Each by-product had one amino-acid missing (⁷²Ile and ⁷³Asn, respectively) from the sequence of ACP(65-74).     

Synthesis of condensed quinoxalines. Part II

A novel efficient synthesis of fluorescent, fused quinoxalines was achieved. 7-Triazolyl-1,4-dioxino[2,3-b]-quinoxalines were synthesized by the diazotisation of 7-amino-1,4-dioxino[2,3-b]quinoxaline and coupling with selected aromatic amines followed by air oxidation. Diazotised aryl amines were coupled with 7-amino-1,4-dioxino[2,3-b]quinoxalines followed by subsequent air oxidation afforded 1,4-dioxino[2,3-b]quinoxalino-[6,5-d]1,2,3-triazoles. 7-Amino-1,4-dioxino[2,3-b]quinoxaline was condensed with conjugated enol ethers followed by cyclization in dowtherm resulted in 1,4-dioxino[2,3-b]quinoxalino[6,5-b]pyridines.     

Fibrillation Tendency of Cellulosic Fibers. Part 1: Effects of Swelling

The fibrillation tendencies of various cellulosic fibers in aqueous solution containing alkali metal hydroxide and ethanol were evaluated with two specific parameters: the critical point of fibrillation (CPF_conc.), that is a concentration of swelling agent where the fibrillation begins, and the ratio of initial increase in fibril number to increase in concentration of swelling agent (I_i). The CPF_conc. and the I_i are defined as fibrillation stability and fibrillation sensitivity to swelling agent, respectively. Lyocell fiber (CLY1) has the smallest CPF_conc. and the largest I_i, representing the lowest fibrillation stability and the highest fibrillation sensitivity, leading to the highest fibrillation tendency in CLY1 among the fibers tested. Although crosslinking improved fibrillation stability in lyocell as compared to modal, the fibrillation stability remained higher owing to the high water capacity and the high affinity for alkali. In alkali solution at the same concentration CLY1 fibrillation increased in the order of LiOH > NaOH > KOH. However, the plot of fibril number against solvent retention value of CLY1 in different alkaline solutions gives a slope of 110 count · g/cm³ regardless of alkali type, the critical degree of swelling for CLY1 with no fibrillation was 0.62 cm³/g in alkali solutions and 0.45 cm³/g in ethanol/water mixture.     

Tea Bags for Fmoc Solid-Phase Peptide Synthesis: An Example of Circular Economy

Peptide synthesis is an area with a wide field of application, from biomedicine to nanotechnology, that offers the option of simultaneously synthesizing a large number of sequences for the purpose of preliminary screening, which is a powerful tool. Nevertheless, standard protocols generate large volumes of solvent waste. Here, we present a protocol for the multiple Fmoc solid-phase peptide synthesis in tea bags, where reagent recycling steps are included. Fifty-two peptides with wide amino acid composition and seven to twenty amino acid residues in length were synthesized in less than three weeks. A clustering analysis was performed, grouping the peptides by physicochemical features. Although a relationship between the overall yield and the physicochemical features of the sequences was not established, the process showed good performance despite sequence diversity. The recycling system allowed to reduce N, N-dimethylformamide usage by 25–30% and reduce the deprotection reagent usage by 50%. This protocol has been optimized for the simultaneous synthesis of a large number of peptide sequences. Additionally, a reagent recycling system was included in the procedure, which turns the process into a framework of circular economy, without affecting the quality of the products obtained.     

Aromatic Amines in Organic Synthesis. Part II. p-Aminocinnamaldehydes

Ten derivatives of p-aminocinnamic aldehydes were prepared from the reaction of either aromatic amines with dimethylaminoacrolein or benzaldehydes with acetaldehyde. Their chemical structure and purity were verified by ¹H NMR, ¹³C NMR and IR spectroscopic methods. We found that the synthesis applying dimethylaminoacrolein as the reagent gets better yields than the one based on the reaction with acetaldehyde. The yields of the cinnamic aldehydes varied according to the type of the amino group and the number and position of the substituents. The basic spectroscopic properties of the p-aminocinnamic aldehydes are also described since the compounds may be a precursor for the synthesis of dyes for diverse applications, e.g., in medicine and optoelectronics.     

Synthesis and characterization of branched polystyrene. Part II. Fractionation

Fractionations have been carried out by a column-elution method on mixtures of linear and branched polystyrene. These had been prepared by anionic polymerization followed by a coupling reaction to form star-shaped branched polymers. Therefore, the components of the mixture were each of narrow distribution, and their molecular weights differed from each other as multiples of the original single chain length. For single chains in the 25,000–30,000 molecular weight range, separations were accomplished in which the multiples (number of branches) were 1, 2, 4, and 6. By this means, virtually monodisperse samples of the branched polymers could be isolated.     

A Novel Hydrazine Linker Resin and Its Application for the Solid-Phase Synthesis of alpha-Branched Primary Amines

A novel hydrazine linker resin for solid-phase organic synthesis has been developed. Starting from Merrifield resin, the new N-butyl-N-methylpolystyrene-hydrazine linker is prepared in three steps. Polymer-supported hydrazones, readily prepared from aldehydes and the hydrazine resin, react with alkyl- and arylorganolithium reagents under 1,2-addition to the C-N double bond to afford the corresponding hydrazines. Release from solid support was achieved by reductive N-N bond cleavage using the borane-tetrahydrofuran complex. The resulting alpha-branched primary amines were protected as their amides or carbamates, respectively, and, after purification, were obtained in good overall yields and in high purity (12 examples).     

Quantitative Determination of Resin Loading in Solid-Phase Organic Synthesis Using (13)C MAS NMR

The use of quantitative carbon nuclear magnetic resonance spectroscopy ((13)C NMR) for the determination of resin loadings has been investigated. Magic angle spinning (MAS) NMR spectra have been obtained for solvent-swollen resins on a conventional 7 mm CP/MAS probe using the two pulse phase modulation (TPPM) proton decoupling sequence. Loadings of resin-bound organic compounds were evaluated via addition of tetrakis(trimethylsilyl)silane as reference or using the carbon resonances of the polymeric resin material as an internal standard. Results for several functionalized Wang and trityl resins are consistent with those obtained using well-established analytical methods. The (13)C NMR method has interesting applications in the field of solid-phase organic synthesis (SPOS), since no functional group acting as a support for the attachment of a quantifiable chromophore must be available in the material of interest.     

脲醛树脂合成实验的改进

对中学教材中脲醛树脂制取实验中存在的结论性错误进行了澄清,对大学有机化学实验中脲醛树脂合成实验进行了合理的改进,并对实验过程中的注意事项包括原料配比、酸的选择、pH的确定、温度的选择进行了探索,最终所得工艺条件具有实验效果明显、容易操作及实用性强等诸多优点,适合新时期教改的需要。     

Synthesis of heterocycles. Part II. New routes to acetylthiadiazolines and alkylazothiazoles

Methylglyoxalyl chloride arylhydrazones (III) react with an ethanolic solution of thiourea to give 2-amino-4-methyl-5-arylazothiazoles (XII) instead of the expected 2-acetyl-4-aryl-5-imino-Δ²-1,3,4-thiadiazolines (V) which were obtained from III and potassium thiocyanate. 3-Thiocyanato-2,4-pentanedione (IV) coupled with diazotized anilines to give V. The postulated routes to formation of V and XII from III are given. Nitrosation of V gave the corresponding N-nitroso derivatives (VI) which decomposed upon refluxing in dry xylene to give 2,4-disubstituted-Δ²-1,3,4-thiadiazolin-5-ones (VII). Boiling of either V or VI with hydrochloric acid gave the hydrochloride salt (VIII). The thiadiazolines V gave the respective N-acyl derivatives (IX) and (X) with acetic anhydride and benzoyl chloride in pyridine.     

On-Site Determination of Methylmercury by Coupling Solid-Phase Extraction and Voltammetry

A measurement and speciation procedure for the determination of total mercury (Hg_TOT), inorganic mercury (Hg_IN), and methylmercury (CH₃Hg) was developed and the applicability for on-site determination was demonstrated. A simple, portable sample pretreatment procedure was optimized to extract the analytes. Home-made columns, packed with a new sorbent material called CYXAD (CYPHOS 101 modified Amberlite XAD), were used to separate the two forms of the analyte. Hg_TOT and CH₃Hg were determined by anodic stripping voltammetry (ASV), using a solid gold electrode (SGE). Two certified reference materials (BCR-463 Tuna Fish and Tuna Fish ERM-CE 464) and eight fresh fishes were analyzed. Then, the results that were obtained following the optimized portable procedure were compared with the concentrations obtained, using a direct mercury analyzer (DMA). This quantification, using the two techniques, demonstrated the good performance of the proposed method.     

Chemistry of Diamantane Part II. Synthesis of 3,5-Disubstituted Derivatives

Although chemical¹ and microbiological² methods for functionalisation of one or more of the bridgehead positions of diamantane are available, there have been no reports of substitution reactions at the methylene positions apart from that of the preparation of diamantanone (1)¹ by sulphuric acid oxidation of the hydrocarbon. There are three structural arrangements possible for a non-bridgehead disubstituted diamantane, but the synthetic route described here leads exclusively to 3,5-disubstituted derivatives.

When treated with sodium azide in cold methanesulphonic acid diamantanone (1) underwent a Schmidt fragmentation-recyclisation reaction of the type described by Sasaki et al.,³ yielding a compound which was not isolated but which was presumed to be the keto-mesylate (2) since treatment of the reaction mixture with sodium hydroxide caused a second fragmentation and the final product was the unsaturated acid (3) in 41% yield. The structure of the acid is based on the spectral data and on subsequent chemical transformations. The normal Schmidt rearrangement product, which is probably a mixture of the two possibilities (4) and (5), was also isolated in 50% yield. The unsaturated acid was readily recyclised under acidic conditions. Use of 96% sulphuric acid resulted in the formation of the lactone (6), but use of hot 50% sulphuric acid furnished 5ax-hydroxydiamantan-5-one (7) as the preponderant product (82%). That the hydroxyl-group occupied the axial config-