G. Jung

Oxidative phenol coupling—tyrosine dimers and libraries containing tyrosyl peptide dimers

Abstract The principles of phenol oxidation are outlined and summarized. Various procedures were used to dimerize tyrosine derivatives, especially linear tripeptides and cyclohexapeptides, via cross-linking of their phenolic side-chains. The coupling was performed by potassium hexacyanoferrate(III), phenyliodine(III)-bis(trifluoroacetate), vanadium(V)-oxyfluoride or horseradish peroxidase. The individual dityrosine and isodityrosine derivatives obtained in preparative scale, as well as the peptide-dimer libraries generated, were characterized by HPLC and electrospray ionization mass spectrometry. Further analyses were carried out by NMR spectroscopy, fluorescence spectroscopy and gas chromatography.

Gas chromatographic determination of the configuration of isovaline in antiamoebin, samarosporin (emerimicin IV), stilbellin, suzukacillins and trichotoxins

SummaryThe D-(resp. R) configuration of isovaline (=2-ethylalanine) was proved for the peptide antibiotics antiamoebin, Tü 165 (CBS 382.62), stilbellin, samarosporin (=emerimicin IV), suzukacillin B (A), trichotoxin A-40 and A-50. This contradicts the previously reported L-configuration for isovaline in antiamoebin and emerimicin IV. The configuration was determined by GC of the N-trifluoroacetyl-isovaline n-propyl ester on glass capillary columns coated with the chiral stationary phase N-propionyl-L-valine tert.-butylamide polysiloxane (Chirasil Val). The D-configuration of the isovaline from trichotoxin A-40 was also established independently using GC of N-pentafluoro-propionyl-isovaline (+)-3-methyl-2-butyl esters on glass capillary columns coated with OV 17.

Oxoammonium Resins as Metal-Free, Highly Reactive, Versatile Polymeric Oxidation Reagents

Polymer-supported oxidation of alcohols was conducted very efficiently by employing oxoammonium salts, the reactive intermediates in TEMPO oxidations (TEMPO=2,2,6,6-tetramethylpiperidinoxyl). These highly reactive salts (see scheme; X=Br, Cl) could be prepared and isolated on the polymeric support, and were used for the conversion of single compounds as well as of complex mixtures of alcohols.

(−)-isovaline: confirmation of its D-(R)-configuration by X-ray analysis of its N-chloroacetyl derivative

Abstract The N-chloroacetyl derivatives of (−)-isovaline 1 crystallizes in space group P21 with Z = 4 and a = 10.675(6), b = 7.698(4), c = 11.739(2) A and β = 97.32(4)°. The structure was solved by the heavy atom method and refined to R = 0.0718 and RG = 0.0991 with 1890 independent reflexions (F0 > 0). The absolute configuration of 1 was determined as R by application of the Hamilton test with two data sets (CuKα and MoKα-radiation). There are two independent molecules 1 showing flat backbone confirmations, which include weak intramolecular bifurcated hydrogen bonds. Strong intermolecular hydrogen bonds determine the crystal packing, in which antiparallel chains of single molecules run along [010]. The (R)-assignment is in agreement with the order of elution ( d before l ) of enantiomers of N-trifluoroacetyl- dl -isovaline-n-propyl ester on glass capillaries coated with the chiral phase N-propionyl- l -valine-t-butylamide-polysiloxane.

Untersuchungen zur totalsynthese des ferredoxins—I : Synthese der aminosäuresequenz von C. pasteurianum ferredoxin

Zusammenfassung Die Synthese der Aminosauresequenz von Ferredoxin aus Clostridium pasteurianum nach der Festphasenmethode wird beschrieben. Das Polypeptid wurde isoliert und charakterisiert als S-Sulfonat und stimmt in Molekulargewicht, Endgruppenanalyse, UV-Spektrum und Aminosaureanalyse mit dem S-Sulfonat von naturlichem Apoferredoxin uberein.

13C NMR spectroscopic studies on the conformation during stepwise synthesis of peptides bound to solubilizing polymer supports

Abstract The C-13 {C-13-H-1} triple resonance technique allows constitutional and conformational studies on polypeptides bound to mono- and bi-functional solubilizing polyoxyethylene supports. High resolution shows distinct differences between random coil and α-helical conformations. This method is a valuable additional tool for control of the growing peptide during stepwise synthesis on soluble polymeric supports. Examples of partial sequences of the polypeptide antibiotic alamethicin and sequential analogs (Aib-Ala) n demonstrate the applicability for peptide polyoxyethylene esters with mean molecular masses between 2000 and 10,000.

Deuterium-isotopieeffekte auf die 13C-chemischen verschiebungen und kohlenstoff-deuterium kopplungskonstanten in deuterierten verbindungen

Abstract The isotope effects on the 13 C NMR chemical shifts and coupling constants ( 13 C 1 H and 13 C 1 H) have been determined by pulse Fourier transform 13 C NMR investigation at 22·63 MHz for more than 30 common deuterated and protonated solvents. The observed isotope effects correlate with hybridization and electron withdrawal at the coupling carbon within the series of comparable compounds. In agreement with MO-theoretical calculations a linear correlation between the J CD values of CD x groups and the J CH values of the corresponding CH x groups was found. The experimentally determined J CD values show an average deviation from the calculated line J CD = (γ D /γ H )J CH = 0·154 ×J CH on the order of± 1 Hz.

Resolution of sulphur-containing amino acids by Chiral phase gas chromatography

SummaryMethyl esters of the pentafluoropropionyl-amino acid derivatives of the tetrafunctional, sulphur-bridged, stereoisomeric lanthionines, cystathionines and β-methyl-lanthionines were resolved on glass capillaries coated with the chiral stationary phase N-propionyl-L-valine-N-tert-butylamide-polysiloxane (Chirasil-Val) within 35min. Interestingly, L-cystathionine elutes before its D-enantiomer in contrast to the usual order of emergence on an L-phase. The method was applied to the polypeptide antibiotic nisin, which contains mesolanthionine and 2S,3S,6R-3-methyl-lanthionine.N-Pentafluoropropionyl-S-alkylthiocysteine methyl esters (R=methyl, ethyl, n- and iso-propyl, n- and sec-butyl, n-octyl, neo-pentyl, cyclohexyl-, benzyl-, tolyl-) were separated on Chirasil-Val within 30min. The identity of all derivatives was shown by combined gas chromatography-mass spectrometry.

Chromatographic and mass spectrometric characterization of the structures of the polypeptide antibiotics samarosporin and stilbellin and identity with emerimicin

SummaryThe structural identity of the polypeptide antibiotics, samarosporin I(II) and stilbellin I(II) with emerimicin IV(III) has been established by thin-layer chromatography, quantitative amino acid analysis by ion-exchange chromatography, gas-liquid chromatography of the N-pentafluoropropionyl amino acid n-propyl esters and N,O-bis-pentafluoropropionyl phenylalaninol with quartz capillaries coated with the chiral stationary phase N-propionyl-L-valine-tert-butylamide, and determination of the relative molecular masses and sequence-specific fragments by field desorption fast atom bombardment mass spectrometry. The separation of closely related sequence analogues of the above polypeptides could be achieved by reversed-phase high-performance liquid chromatography with spherical, fully porous octadecylsilyl bonded phases, and 86% aqueous methanol as eluent. The application of both chromatographic and mass spectrometric methods is demonstrated to be most valuable for the characterization of antibiotics with the unusual constituents α-aminoisobutyric acid, isovaline and phenylalaninol. The methology employed is regarded to be applicable to all polypeptide antibiotics of the peptaibol class.

Synthesis of thiazole, imidazole and oxazole containing amino acids for peptide backbone modification.

Novel 5‐ring heterocyclic building blocks are synthesized. These can be incorporated into analogs of peptide antibiotics such as microcin B17, which is a potent DNA‐gyrase inhibitor that exhibits eight thiazole and oxazole moieties. In particular, the syntheses of imidazole and bisoxazole amino acids as novel peptidomimetics are reported, this includes a new procedure for the oxidative conversion of the intermediates oxazoline, imidazoline as well as oxazole–oxazoline into the corresponding heteroaromatic compounds. A mixture of 1,8‐diazabicyclo‐[5.4.0.]‐undec‐7‐ene/carbon tetrachloride/acetonitrile and pyridine proved to be a very effective and mild agent. Copyright