Zur Synthese von Human-Big-Gastrin I und seinem 32-Leucin-Analogon

The preparation of the pure tetratriacontapeptide amide 2 (human big gastrin I) and the analogue Leu³²-human big gastrin I from the crude synthetic materials obtained after deblocking of the overall protected tetratriacontapeptide amide derivatives by means of trifluoroacetic acid is described. The criteria for homogeneity obtained by chromatographic, electrophoretic, enzymatic and spectroscopic methods are reported.

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Abkürzungen HBG-I Human-Big-Gastrin I - LHBG-I 32-Leucin-Human-Big-Gastrin I - HBG-[1-20] N-terminale Teilsequenz [1–20] des Human-Big-Gastrins I - HG-17-I Human-Gastrin I - LHG-17-I 15-Leucin-Human-Gastrin I - HG-13-I Human-Minigastrin I - LHG-13-I 11-Leucin-Human-Minigastrin I Es werden hier die von der IUPAC-IUB Commission on Biochemical Nomenclature empfohlenen Abkürzungen für Aminosäuren und Schutzgruppen verwendet.Andere Abkürzungen.Anm.: Auf Grund der kürzlich erfolgten Strukturkorrektur (R. A. Gregory, H. J. Tracy, J. I. Harris, M. J. Runswick, S. Moore, G. W. Kenner undR. Ramage, Hoppe-Seylers Z. physiol. Chem.360, 73, 1979) sind HG-13-I und LHG-13-I neuderdings richtiger als Des-1-Tryptophan-Human-Minigastrin I bzw. [Des-1-Tryptophan]-11-Leucin-Human-Minigastrin I zu bezeichnen].Vorläufige Mitt.:E. Wünsch, G. Wendlberger, A. Hallett, E. Jaeger, S. Knof, L. Moroder, R. Scharf, I. Schmidt, P. Thamm undL. Wilschowitz, Z. Naturforsch.32c, 495 (1977).3. Mitt.:G. Wendlberger, L. Moroder, A. Hallett undE. Wünsch, Mh. Chem.110, 1407 (1979).     

Zur Synthese von Human-Big-Gastrin I und seinem 32-Leucin-Analogon 3. Mitteilung: Darstellung der allseits geschützten Gesamtsequenzen

The syntheses of the fully protected tetratriacontapeptide amide derivatives corresponding to the proposed primary structure of human-big-gastrin I and its 32-leucine analogue by three different routes are described. In addition, the synthesis of the N-terminal eicosapeptide derivative (sequence 1–20) is reported.

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Andere Abkürzungen DCCD Dicyclohexylcarbodiimid - HONSu N-Hydroxysuccinimid - TFE Trifluoressigsäure - HMPA Hexamethyl-phosphorsäuretrisamid - DMF Dimethylformamid Abkürzungen: Es werden hier die von der IUPAC-IUB Commission on Biochemical Nomenclature empfohlenen Abkürzungen für Aminosäuren und Schutzgruppen verwendet.     

Zur Synthese von Human-Big-Gastrin I und seinem 32-Leucin-Analogon 1. Mitteilung: Darstellung der Teilsequenzen 28–34, 23–27, 21–22 und 15–20

Human-Big-Gastrin I, a peptide hormone of 34 amino acid residues, and the 32-leucine analogue were synthesized. For this purpose six suitable peptide fragments were prepared at first, which subsequently were condensed to the total sequence. In this paper we describe the syntheses of four suitably protected peptide fragments corresponding to the sequences 28–34, 23–27, 21–22 and 15–20 of human-big-gastrin I. For the protection of the side-chain functionstert-butanol derived groups removable in the final step by acidolytic cleavage were used. The -amino-functions were selectively blocked as benzyloxycarbonyl-and 2-nitrophenylsulfenyl-derivatives, respectively.

Abkürzungen: Es werden hier vorwiegend die von der IUPAC-IUB Commission on Biochemical Nomenclature empfohlenen Abkürzungen für Aminosäuren und Schutzgruppen verwendet. Wegen der universellen Anwendbarkeit bedienen sich die Autoren auch der imHouben-Weyl ² niedergelegten und eingehend erläuterten Abkürzungen.DCCD=N,N-Dicyclohexylcarbodiimid,HONSu=N-Hydroxysuccinimid.     

Zur Synthese von Human-Big-Gastrin I und seinem 32-Leucin-Analogon 2. Mitteilung: Darstellung der Teilsequenzen 9–14 und 1–8

The syntheses of the hexapeptide and octapeptide derivative corresponding to the sequences 9–14 and 1–8 of human-big-gastrin I, respectively, are described. The two fragments obtained predominantly by stepwise procedures, represent in the suitably protected form building blocks for the total syntheses of human-big-gastrin I and its 32-leucine-analogue.

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Abkürzungen DCCD Dicyclohexylcarbodiimid - HONSu N-Hydroxysuccinimid - TFE Trifluoressigsäure - DMF Dimethylformamid - DCHA Dicyclohexylamin Es werden hier die von der IUPAC-IUB Commission on Biochemical Nomenclature empfohlenen Abkürzungen für Aminosäuren und Schutzgruppen verwendet. Andere Abkürzungen     

Ternary metal borides [La,Ce,Pr,Nd,Sm] Os4B4 and [Y,La,Ce,Pr,Nd,Sm,Gd,Tb] Ir4B4 with NdCo4B4-type structure

New ternary metal borides with compositionR. E. T ₄B₄ (R. E.=rare earth metal,T=transition metal) have been synthesized within the systems [La,Ce,Pr,Nd,Sm]–Os–B and [Y, La, Ce, Pr, Nd, Sm, Gd, Tb]–Ir–B. All compounds were found to be crystallizing with NdCo₄B₄-type structure. Magnetic measurements (80–300 K,Curie-Weiss behaviour, _p ~ 16K and µ_eff=9.94µ_B for TbIr₄B₄) indicate Y andR. E. elements (except Ce) to be trivalent in these compounds. The crystal chemistry of the isotypic series [Y,R. E.] [Os,Ir]₄B₄ is discussed.

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Ternäre Metallboride. [La,Ce,Pr,Nd,Sm] Os₄B₄ und [Y,La,Ce,Pr,Nd,Sm,Gd,Tb] Ir₄B₄ mit NdCo₄B₄-Struktur

Zusammenfassung Es wurden neue Metallboride der ZusammensetzungR. E. T ₄B₄ (R. E.=Seltenerdmetall,T=Übergangsmetall) innerhalb der Systeme [La,Ce, Pr,Nd,Sm]–Os–B und [Y,La,Ce,Pr,Nd,Sm,Gd,Tb]–Ir–B hergestellt. Alle Verbindungen kristallisieren entsprechend dem NdCo₄B₄-Typ. Magnetische Messungen (80–300K,Curie-Weiss-Verhalten, _p ~ 16K und µ_eff=9.94µ_B für TbIr₄B₄) zeigen an daß Y und dieR. E.-Elemente (ausgenommen Ce) in diesen Verbindungen trivalent sind. Die Kristallchemie der isotypen [Y,R. E.][Os,Ir]₄B₄-Verbindungen wird diskutiert.

     

Synthesis of 2-Substituted Benzthiazoles as Tetramisole Analogs

Zusammenfassung Es wurde eine Reihe 2-substituierter Benzthiazole (3–11) als Analoge des 6-Phenyl-2,3,5,6-tetrahydroimidazo[2,1-b]thiazols (Tetramisol) synthetisiert. Alle dargestellten Verbindungen wurden auf ihre anthelmintische Wirkung überprüft, wobei allerdings keine nennenswerte Aktivität festzustellen war.

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A number of 2-substituted benzthiazoles (3–11) have been synthesized as analogs of 6-phenyl-2,3,5,6-tetrahydroimidazo[2,1-b]thiazole (tetramisole). All the compounds were tested against two intestinal nematodes in rats and hamsters but none showed any noteworthy activity.

Communication No. 2845 from C.D.R.I., Lucknow, India.     

Zur Kenntnis der Reaktionsfähigkeit des unsubstituierten Thiomorpholins und alkylsubstituierter Thiomorpholine. 3. Mitt

A new synthesis of thiomorpholine by ring closure of -chloro--aminodiethylene-sulfide with potassium hydroxide is reported. Numerous reactions of thiomorpholine (1) and, especially, 2-methyl-3-ethyl-thiomorpholine (2) are described such as acylation, diacylation (3–43), reactions with sulfonic acid chlorides (44–52), isocyanates (53–61, 70–75), diisocyanates (62–66, 76–78) and isothiocyanates (67–69, 79–82), alkylation reactions (83–111) and the synthesis of thiomorpholino-dithiocarbamates (112–121).

Teil der Dissertation,E. Wilms, Techn. Hochschule Aachen, 1971.     

Beiträge zur Chemie der Pyrrolpigmente, 42. Mitt. Kraftfeldrechnungen an Gallenfarbstoffen: Die Energiehyperfläche rubinoider Pigmente

The energy hypersurface of rubinoid bile pigments is calculated using a force field model previously described. Two cases are observed. I: The pigment is substituted symmetrically or unsymmetrically by apolar groups. This results in a very shallow energy valley containing several enantiomeric conformers of approximately equal energies. II: Substitution by polar groups, especially in position 8 and 12 of the rubin skeleton, (e.g.–CH₂–CH₂–COOH) is followed by a lock in bonding between such groups and the lactam ring functions. Thereby only two enantiomeric conformers, which are energetically stabilized, are possible. The barrier between these species amounts to about 40 kJ/mol. These results are compared with the experimental facts available so far. An analysis of the corresponding energy hypersurfaces of the diastereomeric forms of (Z,Z)-, (E,Z)-, (Z,E)- and (E,E)-configurations is given as well.

41. Mitt.:Falk H., Müller N., Mh. Chem.112, 791 (1981).     

Darstellung von Organoquecksilber—Stickstoffverbindungen durch Synproportionierung

The exchange reaction ofR ₂Hg and >N–Hg–N< compounds yielding organomercury—nitrogen compounds may be widely applied, as shown here in the synthesis ofN-phenylmercury-amides,-imides,-heterocycles and-triazenes.

     

Crystal structure of (S,S)-diphenylethanediammonium (R,R)-tartrate

Summary The crystal structure of (–)-diphenylethanediammonium-(R,R)-tartrate was determined. From this structure determination, the (S,S) configuration was assigned to the (–)-diphenylethanediamine. The asymmetric unit of the crystal structure contains two units of the title compound plus one molecule of ethanol and one water molecule, which form an intricate network of 19 hydrogen bonds.

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Die Kristallstruktur von (S,S)-Diphenylethandiammonium-(R,R)-tartrat

Zusammenfassung Es wurde die Kristallstruktur von (–)-Diphenylethandiammonium-(R,R)-tartrat bestimmt. Aus dieser Strukturbestimmung ergab sich die Zuordnung der (S,S)-Konfiguration zum (–)-Diphenylethandiamin. Die asymmetrische Einheit der Kristallstruktur besteht aus zwei Formeleinheiten der Titelverbindung sowie einem Molekül Ethanol und einem Wassermolekül, welche ein komplexes Netzwerk von insgesamt 19 Wasserstoffbrücken bilden.

     

Mittlere Schwingungsamplituden der Hexachloro- und Hexabromo-Anionen einiger Lanthanide

Mean amplitudes of vibration for various octahedral complex compounds of the typeLnCl₆ ^3– andLnBr₆ ^3– (withLn=Nd, Eu, Gd, Dy, Er, and Yb) have been calculated, at different temperatures, using known spectroscopic data. The results are briefly discussed and it is found that theLn–Cl andLn–Br amplitude values are highly characteristic.

     

Ylide von Heterocyclen,III Pyridinium-Ylide von Malonylheterocyclen

Reaction of isatoic anhydride with the betaine esters2 or3 represents a new synthesis of pyridinium ylides of type5, which have been previously obtained by several other ways. Treatment of the ylide5 with inorganic acids results in the formation of their pyridinium salts5 a–d. Hydrogenation or dehydrogenation of5 with Pd/C give the piperidylquinoline9 or the betaine10, respectively. Both of them can be prepared by an alternative way. ThepK values of some pyridinium ylides were determined.

II. Mitteilung:Kappe Th., Korbuly G., Stadlbauer W., Chem. Ber.111, 3857 (1978).     

Einwirkung von Schwefel und Ethylenimin auf höhermolekulare symmetrische Ketone, 4. Mitt

The higher molecular ketones, undecanone-6 (1), tridecanone-7 (2), pentadecanone-8 (3), heptadecanone-9 (4) react with ethylenimine and sulfur to give 2,3-disubstituted 5,6-dihydro-1,4-thiazines (9–12) and 2,2-dialkylated thiazolidines (17–20). The reduction of9–12 with formic acid yields the corresponding thiomorpholines13–16 (70–90% yield).9–12 is also obtained by the reaction of -chloro ketones (5–8) and the sodium salt of cysteamine 30–75% yield); cysteamine reacts with1–4 to give the thiazolidines17–20 (37–53% yield).

Teil der DissertationJ. Stalschus, Techn. Hochschule Aachen, 1974.     

Struktur und Farbigkeit von P,P′-Tetra-t-butyl-und P,P′-Tetraphenyl-oxalsäurediphosphid und Derivaten

The unexpected violet colour of P,P-tetraphenyl-oxalic acid diphosphide (3) stimulated the synthesis of the following derivatives: P,P-tetra-t-butyl-oxalic acid diphosphide (2), N,P-tetraphenyl-oxalic acid amide phosphide (4) and P, -triphenyl-glyoxylic acid phosphide (5). The compounds could be prepared by the reaction of the corresponding acyl chlorides with diorganyl-(trimethylsilyl) phosphine; (organyl=t-butyl and phenyl). The electronic transitions of green-blue2 and red5 in the 450–700 nm region are discussed, also theirv C=O in the ir spectrum. These results are interpreted in connection with the molecule structures of2 and3 which have been determined by X-ray crystal structure analysis. In2 the framework P–C(O)–C(O)–P is only slightly distorted from a coplanartrans-position, in3 somewhat more. The bonds at P have the expected pyramidal arrangement. The direction of the lone pairs at the P-atoms, derived from this bond arrangement, is discussed with respect to the electronic transitions in acyl phosphides.

     

Aminoalkoholester von Hydroxyboranen,IX Salicylamid-Bor-Mannichbasen als potentielle Antitumorwirkstoffe

A synthesis of new boron containingMannich bases of salicylamide by reaction of salicylamide, formaldehyde and boron-heterocycles is reported.

VIII. Mitteilung:Stump, R. K., Zimmerman jr., H. K., Schleppnik, A. A., Gutsche, C. D., Liebigs Ann. Chem.667, 18 (1963).     

Der Einfluß großer Salzkonzentrationen auf die Oxydationsreaktion von Fe(phen) 3 2+ mit Ce(IV) in Schwefelsäure

The influence of NaClO₄, NaCl and Na₂SO₄ on the oxidation of Fe(phen) ₃ ²⁺ by Ce(IV) was investigated by means of the stopped-flow method. At the concentrations range of NaClO₄ and NaCl 0.1–1.0M the rate constant values decrease from 1.03·10⁵ to 0.56·10⁵M^–1s^–1 and from 1.08·10⁵ to 0.81·10⁵M^–1s^–1 respectively.In varying concentrations of Na₂SO₄ solutions (0.05–0.35M) the rate constant values decrease from 1.05·10⁵M^–1s^–1 to 0.45·10⁵M^–1s^–1.Taking into account the negative salt effect the mechanism of the reaction progress is proposed.

     

Zur Kenntnis der Reaktionsfähigkeit des Thiomorpholins und alkylsubstituierter Thiomorpholine, 4. Mitt.

Thiomorpholine as well as alkyl substituted thiomorpholines and their Sdioxides, respectively, are transformed into the corresponding N-Aminothiomorpholines by nitrosation (1–5) followed by the reduction with zinc in acetic acid/acetic acid anhydride under simultaneous formation of the corresponding N-acetyl derivates, and hydrolysis by hydrochloric acid (6–9). Examples of this method are described. 4-Aminothiomorpholines and their Sdioxides react with aldehydes or ketones to give azomethines (10–31). Acylation with mono-and dicarbonic acid chlorides leads to the N-acyl derivatives32–44.Mannich condensation is also possible. By oxidation with yellow mercury oxide tetracenes are formed (46–47).

Teil der DissertationM. Schmitz, Techn. Hochschule Aachen, 1975.     

Reaktion von 2-(N-Alkyl-p-hydroxyanilino)-1,4-benzochinonen Diazomethan. N-(Alkyl-p-hydroxyanilino)-4,7-indazolchinone und ihre isomeren N-Methylderivate

The reaction of N-alkyl-p-hydroxyanilinobenzoquinones1 a–d, its acetylderivatives1 ₁–c₁ and the methoxyderivative1 a₂ with diazomethan yields in dependence on the reaction-conditions the indazolquinones2 a–d, 2 a₁–c₁ or2a ₂, the1-methylindazolquinones3 a–d and3 ₁–c₁, and finally the methoxy-1-methylindazolquinones5 a–d. The 2-methyl-isomeres6 a–d are formed only in small amounts. Methylation of2 a with dimethylsulfate gives5 a and6 a in the ratio of appr 2 to 1. Acetylation of2 a–d with acetanhydride leads to the N–O-acetylderivatives, which are easily hydrolyzed to2 a₁–d₁ during work up;3 a d yields3 a₁–d₁. The structures are established by the described crossexperiments and by spectroscopy (UV/VIS, IR, NMR).

Herrn Prof. Dr.G. Zigeuner zum 60. Geburtstag gewidmet.     

HPLC Separation of O-Acylated Flavonoids and Biflavones from Some Species of Gymnospermae

Flavonoids present in the extracts from leaves of Pseudotsuga menziesii (Pinaceae), Ginkgo biloba (Ginkgoaceae) and Podocarpus dacrydioides (Podocarpaceae) were separated by use of the reversed phase HPLC method. The analysed compounds belong to different groups of flavonoids – biflavones (amentoflavone, bilobetin, 5–methoxybilobetin, podocarpusflavone A, sequoiaflavone, podocarpusflavone B, ginkgetin, isoginkgetin, sciadopitysin, kayaflavone, hinokiflavone, 2,3–dihydrosciadopitysin, 2,3–dihydroisoginkgetin), O–acylated flavonol glycosides (daglesiosides I, II, III, IV, trans–tiliroside, trans–ditiliroside), flavonol O–glycosides (astragalin, isoquercetin) and flavonol aglycones (kaempferol, quercetin, isorhamnetin). The conditions for flavonoid separation were optimized using various RP–18 columns. The chromatographic resolution was performed with isocratic or gradient elution – optimized by Drylab program or by traditional trial-and-error method, depending on the composition of flavonoid complex.     

Ein Beitrag zur Stereochemie des Arsens in As(III)—Sauerstoffverbindungen

The oxygen coordination sphere around As(III) consists of the three primary oxygen atoms (average As–O distance 1.78₅ Å) and secondary oxygen atoms between 2.70 and 3.37 Å (3.37 Å is the assumed sum of theVan der Waals radii). Reasons are discussed why neither the number (0–3) nor the length of the secondary As–O distances exert an influence on the geometry of the [AsO₃]-group and its As–O distances.