Synthese eines 33gliedrigen Polyaminolactams durch Anwendung der «zip»-Reaktion. 6. Mitteilung über Umamidierungsreaktionen

Synthesis of a 33-membered Polyaminolactam by Use of the Zip-reaction The pentaamino lactam derivative 11 was synthesized from the 13-membered tosylaminolactam 2 . The prolongation of the side chain was achieved using the phthalimido derivative 3 . After removal of the protecting groups the resulting base 11 was treated with KAPA reagent (1,3-propanediamine/potassium-3-aminopropyl-amid). By zip-reaction the 33-membered 13, 17, 21, 25, 29-pentaaza-32-dotriacontanelactam ( 1 ) was formed in 85% yield.     

Die «Zip»-Reaktion: Eine neue Ringerweiterungsreaktion. Synthese von 17-, 21- und 25-gliedrigen Polyaminolactamen. 4. Mitteilung über Umamidierungsreaktionen

The Zip-reaction: A New Method for the Synthesis of Macrocyclic Polyaminolactams The 21- and 25-membered aminolactams 11 and 25 were synthesized from the 13-membered lactam 4 . To introduce the ring enlargement unit (a propylamino group) 4 was N-alkylated using acrylonitrile and the resulting product hydrogenated. Repetition of this reaction sequence gave 3 , which was converted in the presence of base in 90% yield to the ring-enlarged macrocyclic base 11 (Scheme 2). In a similar but stepwise synthesis consisting of two separate ring-enlargement reactions 4 was transformed to 11 via 13 (Scheme 4). Introducing three ringenlargement units into 4 the 25-membered aminolactam 25 was synthesized in 84% yield (Scheme 5). The mechanism of the ring-enlargement reaction is given in Scheme 3. In comparison to a zip-fastener or zipper this reaction is called “zipreaction”.     

Synthese der vier stereoisomeren Dihydropalustraminsäuren. 13. Mitteilung über Schachtelhalmalkaloide

Syntheses of the four stereoisomeric dihydropalustramic acids ([6-(1-hydroxypropyl)-2-piperidyl]acetic acids) (?)-Dihydropalustramic acid, a key product in the structure elucidation of the alkaloid palustrin, has been assigned the threo-cis structure 20 by comparison with the four stereoisomeric (±)-dihydropalustramic acids (threo-cis, threo-trans, erythro-cis, erythro-trans). The latter were synthesized by a new route to α, α′-di-substituted piperidines of this type. Ring closure to the piperidine ring with simultaneous stereospecific formation of the hydroxylated side chain has been achieved by reaction of the stereoisomeric methylesters of 7,8-epoxy-2-decenoic acids with benzylamine. Assignment of the configuration at the piperidine ring is based on careful comparison of the H-NMR. spectra of the N-benzylpiperidines and with the help of lanthanide shift reagents.     

Magnetische Kernresonanz- und «Molecular Orbital»- untersuchungen über die struktur von MEISENHEIMER-komplexen 8. Mitteilung über nucleophile aromatische Substitutionsreaktionen [1]

(1) The NMR. spectra of the stable methoxide addition complexes of 2,4-dinitro-, 2,4,6-trinitro- and 2,4-dinitro-6-cyano-anisole, and the intramolecular (spiro) reaction product of 1-(2′-hydroxyethoxy)-2,4,6-trinitrobenzene demonstrate that these products are MEISENHEIMER (σ?) complexes (addition of base in position 1).     

Mitteilung über Interchalkogenverbindungen. V Mischkristalle der Zusammensetzung TenS8−n

Contribution on Interchalcogen Compounds. V. Mixed Crystals of the Combination Te_nS_8?n H₂ and TeCl₄ react in dichloromethane to yield substances of initially low content of tellurium, which can be enhanced by fractional crystallization to an atomic ratio T:Se = 1:5. The dark red crystals belong partially to the Sß-type partially to the S_γ-type. X-ray investigation on compounds of both types having the composition “TeS₇” show that these are mixed crystals of S₈, TeS₇, and Te₂S₆.     

Notiz zur Konstitution des Laurepukins. 8. Mitteilung über natürliche und synthetische Isochinolin-Derivate

The alkaloid (?)-laurepukine is shown to possess one of the epimeric N-oxide structures 4 or 5 . Oxidation of (?)-pukateine ( 3 ) by hydrogen peroxide gives (?)-laurepukine and, as a second product, 6-epi-laurepukine.     

Über die Konstitution zweier neuartiger «dimerer» Indolalkaloide Pycnanthin und Pleiomutinin 132. Mitteilung über Alkaloide

The «dimeric» indole alkaloid (+)-pycnanthine ( 2 ) has been isolated, along with (+)-pleiocarpamine, (+)-quebrachamine, (+)-macusine B and an unknown alkaloid D from Pleiocarpa pycnantha (K. SCHUM .) STAPF , var. pycnantha M. PICHON. An investigation of its chemical and spectroscopic properties has led to the determination of structure 2 for this base. Its 6′,7′-dihydro derivative has been shown to be identical with the alkaloid pleiomutinine, previously isolated from Pleiocarpa mutica BENTH .     

Umbellamin,ein neues «dimeres» Indolalkaloid 130. Mitteilung über Alkaloide [1]

Umbellamine (f; C₄₁H₄₈N₄O₄), a «dimeric» indole-indoline alkaloid, was isolated from the root bark of Hunteria umbellata (K. SCHUM .) HALL . F.; it is probably identical with the alkaloid hunterine (structure unknown) of NeUSS & CONE [14]. Thermolysis yielded (+)-eburnamenine (II), whereas a detailed mass spectrometric study of I, of its O-methyl and O-acetyl derivatives, and also of the derived diol V revealed the presence of a phenolic hydroxy-pseudoakuammigine group as second part, the benzene nucleus of the latter being linked to the C-14 atom of the eburnamenine component (present in the dihydrom form). The n.m.r. study of umbellamine and of its derivatives showed that the phenolic hydroxy group is either at C-10′ or C-11′ and that the dihydroeburnamenyl residue is connected to C-11′ or C-10′ of the pseudoakuammigine residue. A choice between these alternatives was possible by investigation of the hydroxylated base IX arising from the latter component, and obtained in small quantities by treatment of umbellamine with zinc or tin in acid. Its constitution, deduced by uv., n.m.r. and mass spectrometry, suggested that the hydroxy group is fixed at C-11′. If this is correct, the dihydrocburnatnenyl residue is linked to C-10′ of the pseudoakuarnmigine residue. Thus we propose formula I for umbellamine.     

Über die Synthese von Verbindungen mit dem Skelett der Homoproaporphine. 7. Mitteilung über natürliche und synthetische Isochinolinderivate

The synthesis of the tetracyclic spiro compounds 11, 12, 13, 14, 17, 18, 19 and 20 with homoproaporphine skeleton is described. Crucial intermediates are the secondary alcohols 10 and 16 . The structure of the spiro compounds is proved by transformation of 11 into the dihydronaphthalene derivative 24 and NMR.-spectroscopic studies of the latter.     

Massenspektrometrische Identifizierung und Synthese isomerer und homologer Spermidin- und Spermin-Derivate. 25. Mitteilung über das massenspektrometrische Verhalten von Stickstoffverbindungen. 161. Mitteilung über Alkaloide

Synthesis of isomeric and homologous spermidine and spermine derivatives and their identification by mass spectrometry. The structure of homologous and isomeric spermidines and spermines follows from mass-spectroscopical analysis of their peracetyl (see text, footnote 3) (Table 1) or tosyl-acetyl (Table 2) derivatives. In the case of the peracetyl compounds, triads of peaks are recorded which, according to the number of methylene groups between the nitrogen atoms, show mass numbers characteristic for each of the substances (Scheme 1, ions b , d , e and c ). On the basis of cyclic ions of type f (Scheme 2), occurring in the mass spectra of N-acetyl derivatives, tosylated on a secondary amino nitrogen atom, deductions can be drawn as to the number of methylene groups between neighbouring tosylated and acetylated nitrogen atoms in these compounds.     

Lokalisierung der Ketogruppe in Inandenin-onen. 160. Mitteilung über Alkaloide

Localization of the keto group in Inandenin-ones . By Schmidt degradation of the spermidine alkaloids inandenine-12-on ( 1 ) and inandenine-13-on ( 2 ) from Oncinotis inandensis followed by hydrolysis, acetylation and esterification four different types of products were obtained: the dicarboxylic diesters 9 and 10 , the ω-amino-carboxylic esters 11 and 12 , the acetylated polyamines 14 and 15 , and the acetylated triaminecarboxylic esters 16 and 17 . By GLC. and mass spectral analysis of these degradation products, and by comparison with synthetic compounds it was possible to confirm the structures 1 and 2 . The same alkaloid mixture ( 1+2 ) was obtained from the leaves of Oncinotis nitida BENTH .     

Beiträge zur Chemie der 4-Hydroxyindol-Verbindungen 10. Mitteilung über synthetische indolverbindungen [1]

Catalytic hydrogenation of 4-benzyloxyindoles does not stop at the hydroxyindole stage, but slowly leads to the 4,5,6,7-tetrahydro-4-ox-indoles 3 . Some procedures for the selective preparation of 4-hydroxyindoles 2 are described. When 4-benzyloxy-3-(1-hydroxyimino-ethyl)-indole ( 4c ) is warmed with trifluoroacetic acid, cleavage of the ether results as well as partial benzylation of the free hydroxyindole in the position 5 ( 5a, 5b ); no Beckmann rearrangement is observed. Esters of 4-benzyloxy-indole-2-carboxylic acid are formylated with POCl₃/dimethylformamide in the 7-position to give 7a ; in the corresponding dimethylamide, on the other hand, the formyl group enters the 3-position to give 8 . Both 4- and 7-hydroxyindole are oxidized with Frémy's salt to the 4, 7-quinone 13 ; on reduction this yields 4, 7-dihydroxyindole 14 , which is tautomerized by base-catalysis to 5, 6-dihydro-4, 7-dioxo-indole 15 . The course of the etherification of 4-hydroxyindoles with epichlorohydrin and related compounds is described, and the resulting side-chains are characterized by their NMR. spectra.     

Über in 6-Stellung basisch substituierte Morphanthridine. 8. Mitteilung über siebengliedrige Heterocyclen

Morphanthridines III with a basic substituent in position 6, which show neuroleptic activity, have been synthesised as follows: Chlorination of the lactams I with POCl₃ gave the iminochlorides II, which were converted by bases to the amidines III. The 11-oxo-morphanthridines VI and VII were synthesised using the same procedure, 2-(1-methylpiperazine-4-carbonyl)-2′-amino-benzophenone (XI) was obtained directly from the 6-chloro-11-oxo-morphanthridine (V) or by extended heating of VI with N-methylpiperazine. Reduction of the 11-oxo-compounds VI and VII with NaBH₄ gave the 11-hydroxy-compounds IX and X. 3-(2-aminophenyl)-phtalide (VIII) resulted from the acid hydrolysis of IX.     

Synthese von threo-cis/threo-trans- und erythro-cis/erythro-trans-Dihydropalustrin. 17. Mitteilung über Schachtelhalmalkaloide

Synthesis of threo-cis/threo-trans- and erythro-cis/erythro-trans-dihydropalustrin The first synthesis of a threefold protected spermidine, namely ³-benzyloxycarbonyl-N¹-phthaloyl-N²-tosylspermidin ( 9 ) is presented. Each of the protecting groups can be removed selectively. After hydrazinolysis the resulting N³-benzyloxy-carbonyl-N²-tosylspermidine ( 10 ) has been condensed with methyl (2 E)-cis-7,8-epoxy-2-decenoate to the threo-cis/trans piperidines 17 , and with methyl (2 E)-trans-7,8-epoxy-2-decenoate to the erythro-cis/trans piperidines 17 , respectively. After catalytic removal of the Z group, the resulting aminoesters 13 and 18 , in a melt with imidazole, underwent ring closure to the 13-membered lactames 14 and 19 , respectively. reductive deprotection of the N-tosyl group with sodium/ammonia led to the stereoisomeric palustrines 15 and 20 , respectively.