Helmut Lackner

Crystal Structures of Actinomycin D and Actinomycin Z3

Untwinned single crystals of the actinomycins D and Z3 that diffracted to atomic resolution could be obtained for the first time. Low-temperature data collection and a new ab initio method for solving the structures led to precise crystal structures which showed, for example, that the unit cell of actinomycin D contains three molecules, two of which are present in the form of a hydrogen-bridged dimer related by a pseudo-twofold axis (see picture).

Synthese von 8-azajuglon (4-hydroxy-5,8-chinolinchinon)

Abstract Structures of substituted quinolinequinones are found in natural products and important drugs. A convenient synthesis of the interesting, new 8-azajuglone (4-hydroxy-5,8-quino-linequinone) ( 6a ) and some useful intermediates ( 4 , 5 ) is described. All NMR- and other data prove the juglone-like structure of 6a .

Die NMR-spektroskopische Identifizierung von Barbituraten

SummaryNMR-spectroscopy offers a highly sensitive analytical method without loss of substance and with great informational value for solving problems in forensic toxicology. An interesting area of application of this method is the identification and quantitative determination of barbiturates, the NMR-spectra of which are primarily determined by the hydrocarbon side chains.Initial investigations using pure substances showed that barbiturates give very characteristic spectra, whereby quite similar compounds such as isomeres and homologues can definitely be distinguished. Since the NMR-spectra of 30 of the most important barbiturates are clearly different from one another, unknown barbiturates can be positively identified by means of direct comparison of the usually distinct and easily interpreted spectra.Mixtures can be qualitatively and quantitatively analysed without difficulty, and absolute quantitative determinations give good results even by grossly contaminated samples. The sensitivity of the method can be increased by the use of a multi-channel analyzer, and if necessary with special sample tubes, to the point where 20 μg of barbiturate still give analysable spectra.ZusammenfassungDie NMR-Spektroskopie bietet sich als hochempfindliches, ohne Substanzverlust arbeitendes Analysenverfahren mit großem Informationswert zur Lösung forensisch-toxikologischer Probleme an. Ein interessantes Anwendungsbeispiel für die eingangs kurz beschriebene Methode schien die Identifizierung und quantitative Bestimmung von Barbituraten, deren NMR-Spektren weitgehend durch die Kohlenwasserstoff-Seitenketten bestimmt werden.Die zunächst mit Reinsubstanzen durchgeführten Versuche zeigten, daß Barbiturate ganz charakteristische Spektren geben, wobei auch sehr ähnliche Verbindungen wie Isomere und Homologe sicher zuzuordnen sind. Da die Spektren der 30 wichtigsten Barbiturate sich alle deutlich voneinander unterscheiden, können unbekannte Barbiturate durch direkten Vergleich der meist recht übersichtlichen und leicht interpretierbaren Spektren einwandfrei identifiziert werden.Gemische lassen sich qualitativ und quantitativ einfach analysieren und absolute quantitative Bestimmungen liefern selbst bei stark verunreinigten Proben gute Ergebnisse. Die Empfindlichkeit der Methode wird durch Benutzung eines Vielkanalanalysators — und gegebenenfalls spezieller Probenröhrchen — soweit gesteigert, daß noch 20 μg Barbiturat gut auswertbare Spektren geben.

Synthese eines verhaltensphysiologisch wirksamen Hexapeptids

1. Gutman, I., Trinajstid, N. : Topics Curr. Chem. 42, 49 (t973), and references therein 2. Schaad, L. J., Hess, B. A.: J. Amer. chem. Soc. 94, 3068 (1972) 3. Gntman, I. : in preparation 4. McCtelland, B. J. : J. chem. Phys. 54, 640 (197t); Outman, I. : Chem. Phys. Letters 24, 283 (1974). 5Graovac, A:, et al. : Theor. chim. Acta 26, 67 (t972) 6. Polansky, O. E.: Mh. Chem. 91,916 (1960) 7. Gutmau, I., Trinajstid, N., Zivkovid, T. : Croat. chem. Acta 44, 501 (1972) 8. Coulson, C. A., Rushbrooke, G. S. : Proc. Roy. Soc. (Edinburgh) A 62, 350 (1948) Synthese eines verhaltensphysiologisch wirksamen Hexapeptids

Structure and Biosynthesis of Isatropolones, Bioactive Amine-Scavenging Fluorescent Natural Products from Streptomyces Gö66

The natural products isatropolone A-C (1-3) were reisolated from Streptomyces Gö66, with 1 and 3 showing potent activity against Leishmania donovani. They contain a rare tropolone ring derived from a type II polyketide biosynthesis pathway. Their biosynthesis was elucidated by labeling experiments, analysis of the biosynthesis gene cluster, its partial heterologous expression, and structural characterization of various intermediates. Owing to their 1,5-diketone moiety, they can react with ammonia, amines, lysine, and lysine-containing peptides and proteins, which results in the formation of a covalent bond and subsequent pyridine ring formation. Their fluorescence properties change upon amine binding, enabling the simple visualization of reacted amines including proteins.

[Propane-diol-(1.3) fatty acid esters as metabolites of postmortal triglyceride catabolism (author's transl)].

SummaryThe investigation of 72 samples of human subcutaneous fat tissue stored in closed small bottles at room temperature showed that every third sample decomposed with the formation of unknown metabolites. The presence of these compounds could already be recognized in the crude lipid extracts by characteristic1H-NMR signals, increasing in intensity with time of storage. After isolation, the unknown metabolites could be identified as di- or mono fatty acid esters of propane-diol-(1.3). Thus, the known scheme of postmortal breakdown of triglycerides is to be supplemented by a further remarkable pathway.ZusammenfassungDie Untersuchung von 72 verschlossen bei Zimmertemperatur gelagerten menschlichen Fettgewebsproben zeigte, daß jede dritte davon unter Bildung unbekannter Metaboliten abgebaut wurde. Die Anwesenheit dieser Verbindungen gab sich bereits im Rohlipidextrakt durch charakteristische, vom Alter der Probe abhängige1H-Kernresonanzsignale zu erkennen. Nach der Isolierung konnten sie als Di- oder Monofettsäureester des Propandiol-(1.3) identifiziert werden. Damit erweitert sich das bekannte Schema des postmortalen Abbaus von Triglyceriden um einen weiteren bemerkenswerten Weg.

Kristallstrukturen von Actinomycin D und Actinomycin Z3

Unverzwillingte, bis zu atomarer Auflosung streuende Einkristalle konnten erstmals von den Actinomycinen D und Z3 erhalten werden. Tieftemperaturmessungen und die Nutzung neuer Ab-initio-Strukturlosungsmethoden lieferten prazise Kristallstrukturen und ergaben, das z. B. die Elementarzelle von Actinomycin D drei Molekule enthalt, von denen zwei als H-Brucken-verknupfte Dimere vorliegen, die uber eine pseudo-zweizahlige Achse in Beziehung stehen (siehe Bild).

Octacidomycine, IV : Neue Totalsynthese von rac-Octacidomycin und strukturverwandten Oligocarbonsäuren / Octacidomycins, IV : A New Total Synthesis of rac-Octacidomycin and Structurally Related Oligocarboxylic Acids

Following a new strategy, an improved total synthesis of the unique antibiotic octacidomycin (1) and of structurally related oligocarboxylic acids was developed (Scheme 1,2). Starting from 3 and the tetraethylester of 1,17-dibromo-6,6,12,12-heptadecane-tetracarboxylic acid (6 ) as a key compound, systematical fragment condensations lead to the nonatriacontanepentadecacarboxylic acid 11 and hence to the 1,3,9,15,21,27,33,39-nonatriacontane-octacarboxylic acid 1. The synthetic pathway can easily be modified and generally be applied for the synthesis of a broad variety of hitherto unknown oligocarboxylic acids or their esters, respectively, and even of cyclic analogues (Scheme 2).

Juglorescein, Juglocombins and Juglochromans: Structure of Juglomycin Dimers from Streptomycetes

Novel juglomycin derivatives with a C28 skeleton were isolated from the Streptomyces strains 815 and GW4184. Juglorescein (1a) and juglocombin A (2a) and B (3a) are C,C dimers of juglomycin C (10) with a five membered ring between the two monomeric moieties. In the juglochromans A-D (4a, 5a, 6a, 6c), two juglomycin C (10) units are connected by C,C and C,O bonds forming a central isochroman or a chroman system. The structures of the new natural products were elucidated by detailed spectra analyses, by comparison of the NMR data with those of related compounds and by biosynthetic considerations. The new natural products were antimicrobially inactive.

Juglomycins G-J: Isolation from Streptomycetes and Structure Elucidation

From the Streptomyces spp. 815 and GW4184, four new 4-juglon-2-ylbutyric acid derivatives, the juglomycins G - J (3a, 4a, 4c, 5c), have been isolated and characterised. The structures were derived from the 1D and 2D NMR data and mass spectra and confirmed by comparison with structurally related compounds. The absolute configuration was deduced from the CD spectra. The new natural products exhibited weak antibacterial activity similar to juglomycin A (5a).