Der Einfluss der O-Acetylierung auf das konformative Verhalten des Kollagen-Modellpeptides (L-Pro-L-Hyp-Gly)10 und von Gelatine

The Influence of O-Acetylation upon the Conformational Behaviour of the Collagen Model Peptide (L -pro-L -Hyp-Gly)₁₀ and of Gelatin (L -Pro-L -Hyp-Gly)₁₀ which can be considered as a model peptide for collagen structure studies has been synthesized by the Merrifield technique. Subsequently, the hydroxyprolin residues have been acetylated by acetic acid anhydride in trifluoroacetic acid. In the same way, the hydroxyl groups of commercial bovine gelatin have been selectively acetylated. The influence of blocking the hydroxyl groups upon the thermal stability of the tripel helix formed by (L -Pro-L -Hyp-Gly)₁₀ and upon the transition temperature and the gel stability of the gelatin has been investigated by the measurement of optical rotation, circular dichroism, molecular weights and gel melting points. The results show that O-acetylation reduces the thermal stability of the collagen-like tripel helices formed in solution by the synthetic peptide and during the gelation process of gelatin. Our experiments support data previously published by various authors indicating that the hydroxyl group of hydroxyprolin plays an important role in stabilizing the collagen tripel helix. The possibility to use O-acetylated gelatin with its reduced gel forming capability for the preparation of plasma substitute solutions is discussed.     

Elektrochemische Decarboxylierung von L.-Threonin- und Oligopeptid-Derivaten unter Bildung von N-Acyl-N,O-acetalen: Herstellung von Oligopeptiden mit Carboxamid-oder Phosphonat-C-Terminus

Electrochemical Decarboxylation of L -Threonine and Oligopeptide Derivatives with Formation of N-Acyl-N, O-acetals: Preparation of Oligopeptides with Amide or Phophonate C-Terminus Derivatives of α-amino acids with two stereogenic centers (cf. L -threonine) and of di-, tri-, and tetrapeptides are electrolyzed in MeOH or AcOH, with formation of N-acyl-N, O-acetals ( 1b – 15b , 20b ), in an anodic oxidative substitution of the COOH by an OR group. The amine ends of the oligopeptides may be benzyloxycarbonyl(Z)- or (tert-butoxy)carbonyl(Boc)-protected. With unprotected dipeptides, an electrolytic decarboxylative cyclization to imidazolidinones ( 18c , 19c ) may also occur (in H₂O/NH₄OAc). The electrolyses are carried out in simple flasks with cooling jackets (‘undivided cell’), using constant current conditions and anodes of Pt or glassy C. The electrolyte is generated in situ by adding 10–20 mol-% of a tertiary amine. Mild acidic hydrolysis of electrolysis products thus obtained may lead to amino-acid amides or peptide amides ( 10c, 11c, 12c, 17c ) with one amino acid less than the starting material. The N, O-acetals from L -threonine and the oligopeptides also react with organometallic nucleophiles such as Grignard compounds (→ 21 – 26 , 29 ), with formation of products in which the original COOH group has been replaced by alkyl or allyl (sometimes even with moderate stereoselectivity). By treatment of the peptide-derived (open-chain) N, O-acetals with trialkyl or triaryl phosphites/TiCl₄ the RO group is replaced by a phosphodiester group in a (non-diastereoselective) Michaelis-Arbuzov-type reaction ( 1d , 1e , 2d – 9d , 5e ). Thus, the two-step sequence of electrolysis and phosphonation converts an oligopeptide derivative to an analogue with a phosphonic-acid end group. The diastereoisomeric N-protected dimethyl and diethyl dipeptidephosphonates (also prepared from the corresponding diaryl esters by Ti(OR)₄-mediated transesterification) could be separated by preparative HPLC (SiO₂, Lichrosorb Si 60, 10 μm); the dextrorotatory isomers of 1d – 3d were assigned L , D -, the laevoratory ones L , L -configuration by hydrolysis to and identification of the known amino and aminophosphonic acids. The results described demonstrate a new simple route leading, from a given oligopeptide, to pure peptide analogues of known configuration.     

13N-NMR spectroscopy. XXXV. Sequence analysis of alternating and random copolyamides made up of aliphatic and aromatic ω-amino acids

Alternating copolyamides of various ω-amino acids were synthesized by base-catalyzed polycondensation of N-isothiocyanatoacyl ω-amino acids in solution. Derivatives of the following amino acids were used: glycine, β-alanine, γ-aminobutyric acid, δ-aminovaleric acid, ε-aminocaproic acid, D ,L -β-aminobutyric acid, trans-4-aminocyclohexane 1-carboxylic acid, 4-aminophenyl acetic acid, 3-aminobenzoic acid, 4-aminobenzoic acid, 3-amino-4-methyl benzoic acid, and 4-amino-3-methyl benzoic acid. The base-catalyzed polycondensation at lower temperatures gave purer products than the bulk condensation at 180–200°C. ¹³C-NMR and natural-abundance ¹⁵N-NMR spectra measured in trifluoroacetic acid demonstrate that in most cases undisturbed alternating sequences were obtained. Strong neighboring residue effects and long-range sequence effects were found in the ¹⁵N-NMR spectra, and structure/shift relationships are discussed. The sequences of copolyamides obtained by copolymerizations of lactams or β-amino acid N-carboxyanhydrides were investigated by both ¹⁵N-NMR and ¹³C-NMR spectroscopy. ¹³C-NMR spectroscopy was found to be more useful if the copolyamides consist of ω-amino acid units of different chain length. However, ¹⁵N-NMR spectroscopy is more suited if the monomer units differ exclusively by their substituents.     

新型L-羟脯氨酸聚合物键合手性固定相的制备及对手性化合物的拆分

以单分散亲水性交联聚甲基丙烯酸环氧丙酯-甲基丙烯酸乙二醇双酯(PGMA/EDMA)树脂为载体,制备新型L-羟脯氨酸聚合物键合高效手性配体交换固定相。该固定相在配体交换分离模式下,以0.2mol/LNaAc和0.1mmol/LCu(Ac)2水溶液(pH5.2)为流动相,柱温为30℃～50℃,对衍生和非衍生的D,L-氨基酸和α-羟基酸等9种手性化合物进行了高效液相色谱拆分。详细考察了流动相pH值、温度、流速和进样量对手性分离的影响,选择了合适的色谱分离条件。结果表明,所拆分的9种手性化合物,有5种手性化合物能得到基线分离,最好的分离因子α=2.32。     

Synthesis of new aromatic polyamides containing α-amino phosphonate with high thermal stability and low heat release rate

The new aromatic polyamides containing α-amino phosphonate were synthesized from phosphorus-based dicarboxylic acid 4 and various aromatic diamines by direct polycondensation reaction. Dicarboxylic acid 4 was successfully synthesized from trimethyl phosphite, 4-aminobenzoic acid and terephthaldehyde via a three-component reaction. The polymerization reaction produced the polyamides 6a–f with high yield and desirable inherent viscosities. The thermal properties of the all samples were investigated by thermo-gravimetric analysis (TGA). The TGA results in N₂ exhibited the 10% mass loss temperatures (T₁₀) in the ranges of 324–345 °C, while the T₁₀ resulted from thermo-oxidative degradation were higher than those. The main data obtained by microscale combustion calorimetry revealed acceptable combustion properties such as very low peak of heat release rate for the synthesized polyamides 6a–f. The all of the results indicated that these polyamides can be potentially utilized as additive for improvement of thermal resistance and combustion behavior of thermoplastic materials.

     

New cyclopeptides from Trichoderma polysporum (Link ex Pers.) Rifai: cyclosporins B, D and E (author's transl)

New Cyclopeptides from Trichoderma polysporum (LINK EX PERS .) RIFAI : Cyclosporins B, D and E Cyclosporins represent a new group of biologically active metabolites produced by Trichoderma polysporum (LINK EX PERS .) RIFAI and other fungi imperfecti. The structures of the main components, cyclosporins A ( 1 ) and C( 3 ) have been determined as neutral cyclic oligopeptides composed of 11 amino acids, among them a new C₉-amino acid [2–4]. In addition, three minor metabolites, cyclosporins B, D and E, have now been isolated and characterized. Chemical investigation, spectroscopic evidence and X-ray analysis led to the structural formulae of cyclosporins B (2) and D (4) . Both compounds have the same sequence of amino acids as cyclosporin A (1) , with the exception of L -α-aminobutyric acid, replaced in cyclosporin B (2) by L -alanine and in cyclosporin D (4) by L -valine, respectively. Cyclosporins undergo a characteristic intramolecular N,O-acyl migration to furnish the corresponding basic isocompounds. The antifungal activities of cyclosporins are reported.     

Stoffwechselprodukte von Mikroorganismen. 174. Mitteilung Eine neue Synthese des Ferrichroms; enantio-Ferrichrom

Metabolites of Microorganisms. A New Synthesis of Ferrichrome; enantio-Ferrichrome The enantiomer of the natural sideramine ferrichrome was synthesized starting from D-ornithine. The cyclohexapeptide (D-Orn)₃-Gly₃ was obtained by conventional methods of polypeptide chemistry. For the oxidation of the δ-amino groups of the D-ornithine residues to hydroxylamino groups the oxaziridine pathway was successful. The final steps - introduction of the acetyl groups and formation of the iron trihydroxamate complex - followed known procedures. The spectroscopic and chromatographic properties of the crystalline product corresponded to those of natural ferrichrome, the optical rotations and CD. curves being opposite. The biological activity of enantio-ferrichrome was similar to that of the natural sideramine.     

N-Boc-Protected α-Amino Acids by 1,3-Migratory Nitrene C(sp3)−H Insertion

N-Boc-protected α-amino acids are synthesized in two steps from linear or branched carboxylic acid feedstocks. In the first step, the carboxylic acid is coupled with tert-butyl aminocarbonate (BocNHOH) to generate azanyl ester (acyloxycarbamate) RCO₂NHBoc. In the second step, this azanyl ester undergoes a stereocontrolled iron-catalyzed 1,3-nitrogen migration to generate the N-Boc-protected non-racemic α-amino acid. This straightforward protocol is applicable to the catalytic asymmetric synthesis of α-monosubstituted α-amino acids with aryl, alkenyl, and alkyl side chains. Furthermore, α,α-disubstituted α-amino acids are accessible in an enantioconvergent fashion from racemic carboxylic acids. The new method is also advantageous for the synthesis of α-deuterated α-amino acids. N-Boc-protected α-amino acids synthesized using this two-step protocol are ready-to-use building blocks.     

Conformational Studies on Potential β-Turn-Forming Model Peptides

The conformational behavior of POE-bound model peptides Boc-(L -Ala)₂-X-Y-(L -Ala)₂-NHPOE (X – Y = L -Pro-Gly ( I ), Gly-L -Ile ( II ); NHPOE = aminopoly(oxyethylene)) as well as of the repetitive hexapeptide of elastin, Boc-L -Val-L -Ala-L -Pro-Gly-L -Val-Gly-A-NHPOE-M ( III ) (A = photosensitive 3-nitro-4-(bromomethyl)benzoyl group; NHPOE-M = aminopoly(oxyethylane) monomethyl ether) has been studied by means of ¹H-NMR and CD spectroscopy. Compounds I and III form a β-turn with Pro and Gly in positions i + 1 and i + 2, respectively, while an aggregated state for II , has been identified. The results are in good agreement with published prediction codes giving experimental evidence for the dominance of short-range interactions to establish secondary structure in solution.     

Synthesis and modification of new biodegradable copolymers: Serine/glycolic acid based copolymers

Serine/glycolic acid-based biodegradable polymers have been prepared by ring-opening homopolymerization of 3-(O-benzyl)-L -serinylmorpholine-2,5-dione, and ring-opening copolymerization of the morpholine-2,5-dione derivative and L -lactide/ϵ-caprolactone. The homopolymerization was carried out in the melt at 165°C for 3 min using stannous octanoate as the initiator and continued at lower reaction temperatures (130–150°C) for 48 h, using a molar ratio of monomer and initiator of 1000 yielded a polymer of M_n = 4000. The polymer prepared by homopolymerization of the morpholine-2,5-dione derivative was composed of alternating protected serine and glycolic acid residues. Random copolymers of serine and glycolic acid and L -lactic acid/ϵ-caprolactone were synthesized by copolymerization reaction of 3-(O-benzyl)-L -serinylmorpholine-2,5-dione and lactide or ϵ-caprolactone in the melt at 165°C for 3 min and further reaction at 130°C using stannous octanoate as an initiator. The polymers were deprotected and functionalized through the side chain hydroxyl group of serine residues with an acrylate moiety for applications in injectable drug delivery, cell encapsulation. © 1997 John Wiley & Sons, Inc. J Polym Sci A: Polym Chem 35 : 1901–1907, 1997     

Die kinetische polarographische Stufe des Urans in Gegenwart von Chlorat-Ionen

An increase of the 2nd polarographic uranium(VI) wave has been observed in the presence of chlorate ions in HClO₄–NaClO₄, or HClO₄–NaClO₄–NaCl supporting electrolyte, resp. The polarographic measurements at different temperatures and at various perchloric acid concentrations show that this increase is due to a kinetic U(III)-U(IV) current. The activation parameters of the U(III)-U(IV) oxidation reaction with ClO₃ ^– have been calculated usingKautecky's method.The approximately 5fold increase of the 2nd polarographic wave allows the determination of small amounts of uranium (10^–5–10^–6 mole/l).

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Conformational Dependence of One-Bond Cα,H Spin Coupling in Cyclic Peptides

Conformational effects on the one-bond C_α, H coupling constant have been studied in cyclic oligopeptides containing glycine, alanine, sarcosine and proline. The conformational contribution to ¹J (C_α, H) can be described as being composed of a positive hyperconjugative term from the neighbouring N-p_z orbital and a negative one from the carbonyl π-system. For glycyl units, a quantitative relation between ¹J (C_α,H) and the vicinal interorbital angles Φ′ and Ψ′ is derived with maximum values ΔJ (Ψ′) = + 14.0 Hz and ΔJ (Ψ′) = ?4.9 Hz. Applications to conformational analysis of cyclo (L -Pro-Gly)₃, cyclo (D -Ala-D -Ala-L -Ala-D -Ala-L -Ala-L -Ala) and cyclo (Sar)₈ are presented.     

Synthese von ‘D-Isothreonin’ und ‘L-Alloisothreonin’ aus L-Alanin

Synthesis of ‘D -Isothreonine’ and ‘L -Alloisothreonine’ Starting from L -Alanine Starting from L -alanine, ‘D -isothreonine’ ( = (2R, 3S)-3-amino-2-hydroxybutanoic acid) and ‘L -alloisothreonine’ ( = (2S, 3S)-3-amino-2-hydroxybutanoic acid) were synthesized.     

Synthese von Haschisch-Inhaltsstoffen. 5. Mitteilung

A (?)-Δ⁸-6a,10a-trans-tetrahydrocannabinol analogue, with a methyl-(3-dimethyl-amino-propyl)-amino side-chain instead of the n-pentyl radical in the naturally occurring product, has been synthesized by condensing 5-methylamino-resorcinol tosylate with (+)-trans-p-2,8-menthadien-1-ol.     

Selenium‐Modified Microgels as Bio‐Inspired Oxidation Catalysts

Active colloidal catalysts inspired by glutathione peroxidase (GPx) were synthesized by integration of catalytically active selenium (Se) moieties into aqueous microgels. A diselenide crosslinker (Se X‐linker) was successfully synthesized and incorporated into microgels through precipitation polymerization, along with the conventional crosslinker N,N′‐methylenebis(acrylamide) (BIS). Diselenide bonds within the microgels were cleaved through oxidation by H₂O₂ and converted to seleninic acid whilst maintaining the intact microgel microstructure. Through this approach catalytically active microgels with variable amounts of seleninic acid were synthesized. Remarkably, the microgels exhibited higher catalytic activity and selectivity at low reaction temperatures than the molecular Se catalyst in a model oxidation reaction of acrolein to acrylic acid and methyl acrylate.     

Kinetik und Mechanismus der Substitutionsreaktionen von Komplexverbindungen, 47. Mitt.: Aquationskinetik descis-[Co(en)2Cl (m-Toluidin)]2+ in sauren Lösungen

The complex salt [Co(en)₂Cl(m-toluidine)](NO₃)₂ has been synthesized and itscis configuration has been proved on the basis of i.r. spectra. The aquation kinetics of the complex ion has been studied at 4 temperatures in the presence of various amounts of perchloric acid. Experimental data are explained by assuming the following reaction scheme: the amino complex (I) is in equilibrium with its conjugated base, i.e. with the amido-complex (II). The equilibrium constant seems to be of the order of magnitude of 10^–3. Both forms of the complex ion participate to aquation reactions. For the amino-form an activation energy of H=25.6 kcal/mole and for the amido-form H=20.4 kcal/mole have been found. These data are compared to the kinetic parameters of the aquation reaction of analogous complexes, and they are discussed, by presuming a dissociation mechanism.

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Über die Depolymerisierung von Poly-(R)-3-hydroxy-buttersäureester (PHB)

On the Depolymerization of Poly-(R)-3-hydroxy-butanoate (PHB) From cell-free PHB or from dried cells of Alcaligenes eutrophus H 16, which had been grown in an aqueous fructose solution, enantiomerically pure methyl, ethyl, butyl or β-methoxyethyl (R)-3-hydroxy-butanoates are obtained in yields ranging from 75–90% (0.1 to 70 g scale). The depolymerization is achieved by heating the PHB-containing materials to temperatures of 80–160° in the corresponding alcohol with or without the cosolvent dichloroethane in the presence of either sulfuric acid or tetraethoxytitanium catalyst. Since (S)-3-hydroxy-butanoates are also readily obtained (by yeast reduction of aceto-acetates), starting materials derived from 3-hydroxy-butyric acid now belong to the especially useful group of synthetic building blocks which are available in both enantiomeric forms.     

Stoffwechselprodukte von Mikroorganismen. 190. Mitteilung. Über das 4-Oxo-homotyrosin,ein Abbauprodukt des Echinocandins B

D , L -4-Oxo-homotyrosine was synthesized by the acetylaminomalonic ester pathway. The optical resolution was carried out by means of the enzyme acylase I. The L -configuration of the enzymatically produced amino acid was confirmed by degradation to L -aspartic acid. 4-Oxo-homotyrosine obtained by degradation of the polypeptide antibiotic echinocandine B has D -configuration, but his optical purity is low. A hypothetical explanation for its formation from the (2 S, 3 S, 4 S)-3,4-dihydroxyhomotyrosine residue of echinocandine B is proposed.     

A novel 3D lead(II) organometallic framework with four lead(II) nuclei as a secondary building unit: Synthesis and characterization

A new 3D layered compound, [Pb₂(L)₂H₂O] _n (L is phenylmalonic acid) was hydrothermally synthesized and characterized by single-crystal X-ray diffraction. In the compound, lead has four coordination modes. The compound has formed a 2D surface shape structure through these coordinate modes with the ligand, and this 2D layer piles through C-H...π forms the 3D compound.     

Effects of polyethylene spacer length in polymeric electrolytes on gelation of ionic liquids and ionogel properties

Polymer electrolytes containing N,N′-(trans-cyclohexane-1,4-diyl)dibenzamide linkages, polyethylene ((CH₂)_m, m = 2, 4, 10) spacers, and bis(trifluoromethanesulfonyl)amide (TFSA) or bis(fluorosulfonyl)amide (FSA) counteranions (polymer abbreviation: CDBAm•X; m = 2, 4, 10; X = TFSA, FSA) have been synthesized, adding to our previous report (m = 6). In addition, their ability to effect the gelation of six ionic liquids and the properties of the resulting ionogels have been examined. The polymers, except for CDBA10•TFSA, effect the gelation for all ionic liquids used in this study at fairly low concentrations (0.9–50 g/L). Ionogel ionic conductivity is not dependent on the spacer length, but does decrease slightly as increasing amounts of the gelatinizer are introduced. In contrast to ionic conductivity, the temperatures at which these ionogels transition into isotropic fluids is dependent on the spacer length; the gel composed of [EMI][FSA] and 100 g/L of CDBA6•FSA transforms at 120 °C, while the gel composed of [EMI][FSA] and 5 g/L of CDBA2•FSA does not transform into a sol even when temperatures become 155 °C. In brief, ionogel heat resistance can be improved by changing the spacer length of the polyelectrolyte. Finally, it has been determined using cyclic voltammetry that the potential window of the polyelectrolytes is particularly wide, ranging from −1.6 to 2.5 V. © 2014 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2015 , 53, 249–255