Potentielle Antineoplastica, 6. Mitt.1) Synthese von Hexestrolderivaten mit alkylierender Seitenkette

Potential Antineoplastics, VI: Synthesis of Hexestrol Derivatives with Alkylating Side Chains The N-mustard derivative 9 and the triazene 19 were prepared by total synthesis.     

Potentielle Antineoplastica, 1. Mitt. Cyclophosphamidanaloge 2-Arylamino-tetrahydro-2H-1,3,2-oxazaphosphorin-2-oxide

Arylaminotetrahydro-2H-1,2,3-oxazaphosphorine 2-oxides, Analogues of Cyclophosphamide The cyclophosphamide derivatives 7--11 without the mustard residue are synthesized and characterized by UV, IR, ¹H-NMR and mass spectroscopic measurements. 7 is not active against the Walker carcinoma 256 of the rat, and no formation of acrolein is observed during the incubation of 7 with the mixed function oxidase system in vitro.     

Potentielle Antineoplastica, 5. Mitt. Darstellung von N,N-Bis(2-chlorethyl)-5-[1-ethyl-2-(4-methoxyphenyl)-2-butenyl]-2-methoxyanilin

Potential Antineoplastics, V: Synthesis of N,N-Bis(2-chloroethyl)-5-[1-ethyl-2-(4-methoxyphenyl)-2-butenyl]-2-methoxyanilin The nitrogen mustard compound 23 is prepared from 6 by total synthesis. The isomeric stilbene compound could not be obtained, since dehydration of the intermediate 20 yields 21 rather than the stilbene derivative 24 . Dehydration of the homologous intermediate 25 also does not result in the stilbene derivative 27 , but in the 1-pentene derivative 26 . All compounds are characterized by UV, IR, ¹H-NMR and mass spectroscopy.     

Synthese von substituierten Phenylcinnolyl-Sulfiden und - Sulfonen 2. Mitt. Cinnoline

The Synthesis of Substituted Phenyl Cinnolyl Sulfides and sulfones Four new phenyl cinnolyl sulfides have been prepared by condensing 4-chloro-6,7-dimethoxycinnoline with substituted thiophenols in presence of sodium ethoxide in nitrogen atmosphere. The sulfides thus obtained and eight other sulfides have been oxidised to their corresponding N-oxide sulfones by hydrogen peroxide in acetic acid.     

Chinon-Amin-Reaktionen, 16. Mitt. Synthese und Eigenschaften C-2/3-substituierter Benzochinoxalinone

Quinone-Amine Reactions, XVI: Synthesis and Properties of 2- and/or 3-Substituted Benzoquinoxalinones Reactions of 1,4-naphthoquinones 1 with 2,3-diaminopropane (4), 1.2-diaminocyclohexane (7)or 2.3-diamino-2.3-dimethylbutane (9)afford the 2-and/or3alkylbenzoquinoxalinones 5/6,8 and 10: Alkylation at C-2 and/or C-3 does no influence the color or the electronic absorption spectra, as can be seen by comparing the 5-Bromobenzoquinoxalinones 5b/6b, 10b and 6-brombenzophenazinone 8b with the 5-bromobenzoquinoxalinone (3b, R³ = H).     

Synthese von 9-Fluorenalkanaminen, 3. Mitt. Stickstoffalkylierte und -acylierte 2-(9H-Fluoren-9-yl)-2-propanamine

Synthesis of (9-Fluorenylalkan)amines, III: N-Alkylated or N-Acylated 2-(9H-Fluoren-9-yl)-2-propanamines The synthesis of N-alkylated or N-acylated derivatives of the fluorene 3a is described. Compound 3b can be prepared via 1b and 2b , but 3c – 3f have to be synthesised by direct alkylation or acylation of 3a . The reaction of 8 with basic agents yields the stable derivative 9 .     

Indole, 2. Mitt. Zur Synthese von 1,3,4-Oxadiazolyl- und Pyrazolcarbonylindolen

Indoles, II: Synthesis of 1,3,4-Oxadiazolylindoles and Indolyl(pyrazolyl)methanones Condensations of 5-chloroindole-2-carbohydrazide (1) with the aldehydes 2a–k yield the acylhydrazones 3a-k . Treatment of 3a–h with boiling acetic anhydride results in the formation of the N-acetyl-1,3,4-oxadiazolylindoles 4a–h within 15 min. Cyclisation of 3i–k requires longer reaction times and gives the N,N′-diacetyloxadiazolylindoles 5i–j . Depending on the type of the p-dicarbonyl compound, the reaction with 1 in boiling toluene/p-toluenesulfonic acid gives indolyl(pyrazolyl)methanones 8a, b , hydrazone 8c or unchanged 1 .     

H2-Antihistaminika, 2. Mitt. Synthese und Pharmakologie α-substituierter Metiamid-Analoga

H₂-Antihistaminics, II: Synthesis and Pharmacology of α-Substituted Metiamide Analogues The synthesis of α-substituted 5-methyl-4- {2-[3-(methyl)thioureido]ethylthiomethyl}-1H-imidazoles 4 from α-substituted 4-methoxymethyl-5-methyl-1H-imidazoles 2 is described. The H₂-antihistaminic activity of the products is reported.     

Polycyclische aromatische Alkaloide, 2.Mitt. Synthese von Onychin und Eupolauridin

Polycyclic Aromatic Alkaloids, II: Synthesis of Onychine and Eupolauridine The total synthesis of onychine ( 5 ) is improved by a new approach to the biaryl 4 . Eupolauridine ( 7 ) is prepared from 5 in a one pot synthesis via the enamine 6 .     

Ringoffene Serotonin-Analoga, 2. Mitt.1) Synthese von 3-(2-Aminophenyl)-propanamin- und 1-(N-Piperidino)-3-(2-aminophenyl)-3-oxo-propan-Derivaten

Ring-Opened Analogues of Serotonine, II: Synthesis of 3-(2-Aminophenyl)propanamine and 1-(Piperidin-1-yl)-3-(2-aminophenyl)propan-3-one and Their Derivatives The synthesis of the title compounds was achieved by Mannich reaction of suitably substituted acetophenones. The preparation of 3-(2-aminophenyl)propanamine and its derivatives requires complete hydrogenation of the carbonyl group of the Mannich bases.     

Chirale 3-Aminopropanole, 1. Mitt. Synthese der Racemate und der Enantiomere

Chiral 3-Aminopropanols, I: Syntheses of the Racemates and the Enantiomers Starting from racem. and optically active disubstituted cyanoacetates the 3-aminopropanols 5a–5d were synthesized. Reduction of the cyanoacetates in two steps was more effective then direct reduction with LiAlH₄. Firstly the nitrile group was catalytically hydrogenated to the amino group, then the ester function was reduced with LiAlH₄. The racem. and optically active 3-amino(cyclohexyl)propanols 5e and 5f were obtained by hydrogenation of 5c and 5d with Pd/C. The absolute configurations of the optically active 3-aminopropanols were deduced from those of the starting compounds.     

Dithio- und Thionester, 57. Mitt.: Synthese N-geschützter β- und γ-Aminosäuredithioester und -thionester

Dithio and Thiono Esters, LVII: Synthesis of Dithio and Thiono Esters of N-Protected β- and γ-Amino Acids The N-Protected β-aminonitriles 1 were transformed into the imidoester or thiolimidoester hydrochlorides 2 or 3 according to Pinner and sulfhydrolyzed with H₂S to give the N-protected β-amino thiono esters 4 or dithio esters 5 . Alkylation of the amides 6 and thioamides 7 yields the iminium salts 8/9 and their sulfhydrolysis again 4/5 . By the first approach N-protected γ-amino nitriles 11 were converted into the γ-amino thiono esters 14 and dithio esters 15 .     

Über potentielle Analgetika, 8. Mitt. Synthese und pharmakologische Testung 3-, 4- und 5-substituierter N-Arylanthranilsäuren

Potential Analgesics, VIII: Synthesis and Pharmacological Test of 3-, 4- and 5-Substituted N-Arylanthranilic Acids For the determination of structure-activity relationships substituted N-arylanthranilic acids were synthesized and tested for their antiinflammatory activity by means of the carrageenin induced paw edema of the rat. The structural requirements for antiinflammatory activity were investigated by determination of the distribution coefficients, by UV spectroscopic measurements and by x-ray structure analysis.     

Chinon-Amin-Reaktionen, 12. Mitt. Synthese und Farbe von Naphthothiazinonen

Quinone-Amine Reactions, XII: Synthesis and Colour of Naphthothiazinones Because of NH/S exchange, naphthothiazinones 8 absorb visible light with a maximum that is shifted towards shorter wavelengths, relative to that of corresponding benzoquinoxalinones 3 , by 10 nm in neutral and by 20 nm in acidic solution. This hypsochromic shift is smaller than for NH/NAc exchange in 4 . Thiazinones 8 are synthetized from naphthoquinones 1 and cysteamin (5) .     

Potentielle Malariamittel, 1. Mitt. 5.8-Dimethoxy-6-diethylaminoalkoxy-chinoline

Potential Antimalarials, I:6-(Diethylaminoalkoxy)-5,8-dimethoxyquinolines Two derivatives of 5,8-dimethoxy-2,4-dimethylquinoline with a 2-diethylaminoethoxy (3a) and a 3-diethylaminopropoxy side chain (3b) at C-6 were synthesized with the aim to study the influence of the replacement of a nitrogen atom in the side chain of the antimalarial 6-aminoquinoline 1 by an oxygen atom on antimalarial activity. Compounds 3a and 3b are inactive against P. vinckei.     

Mehrcyclische Azine mit Heteroatomen in 1- und 3-Stellung, 40. Mitt. Synthese heterocyclischer Immunmodulatoren, 2. Mitt.: 3-Mercaptoalkylthieno[2,3-d]pyrimidin-2,4(1H,3H)-dione: Synthese und Prüfung auf immunstimulatorische Wirksamkeit

Polycyclic Azines, XL: Synthesis of Heterocyclic Immunomodulators, II: 3-Mercaptoalkylthieno[2,3-d]pyrimidine-2,4(1H,3H)-diones: Synthesis and Test for Immuno-stimulating Activity A series of 3-mercaptoalkylthieno[2,3-d]pyrimidine-2,4(1H,3H)-diones 3 was prepared and their immuno-stimulating activity was examined. The title compounds were obtained conveniently by hydrolytic ring cleavage of fused thiazolo- or 1,3-thiazino-thicnopyrimidines 1 under alkaline or acidic reaction conditions. The ms fragmentation of the thieno[2,3-d]pyrimidine-2,4-diones 3 is discussed. In the delayed type hypersensitivity (DTH) test some compounds 3 showed immuno-stimulating activities in the range of isoprinosine.     

Synthese und Reaktionsverhalten neuer tri- sowie tetracyclischer Schwefelanaloga des Indols, 2. Mitt

Synthesis and Reactivity of New Tri- and Tetracyclic Sulfur Analogues of Indole, II: The ketone oxime 1 was rearranged to the lactam 2 . Hydrolysis lead to the amino acid 3b and to the salt 3a . With “Meerwein salt” we received the lactimether 4 , with P₄S₁₀ the thiolactam 5 , with methyl iodide the thiolactim ether 6 . Compound 4 reacted with malodinitril to yield the derivative 7 . From 4 and 1-phenyl-3-methyl-5-pyrazolone we received compound 8 . Substituted hydrazides react with 4 to yield compounds 9a–9h . After heating of 9e, 9d, 9f and 9g we isolated 10, 11, 12 and 13 , respectively. Compound 2 reacts with PCI₅ and NaN₃ to yield the tetrazole 14 . Acylation of benzothiophene (15) with the ester chloride 16 leads to a mixture of the esters 17 and 18 from which we received the acids 19 and 20 . Cyclisation leads to the ketones 21 and 22 . The tropone derivative 28 was synthesized from thiophenol 23 via compound 25 , acid 26 and ketone 27 .     

Zyklische Harnstoffe, 2. Mitt.: Racemate und Enantiomere von Imidazolidin-2-onen Synthese,Konfiguration und sedativ-hypnotische Wirkung

Cyclic Ureas, II: Racemates and Enantiomers of Imidazolidin-2-ones: Syntheses, Configurations and Sedative-hypnotic Activity The racemates and the enantiomers of the imidazolidin-2-ones 2a and 2b , which can be considered as cyclic ureas, are obtained from the racemates and the enantiomers of the hydantoins 1a and 1b by reduction with LiAlH₄/AlCl₃. The enantiomers that are dextrorotating in ethanol possess S-configuration. - In a study with Wistar-rats, 2a and 2b show sedative-hypnotic activity. The enantiomers exhibit marked enantioselective differences in their potency.     

Synthese von 9-Fluorenalkanaminen, 1. Mitt. 2-(9H-Fluoren-9-yl)-2-propanamin und seine kernsubstituierten Derivate

Synthesis of 9-Fluorenealkanamines, I: 2-(9H-Fluoren-9-yl)-2-propanamine and Its Aryl Substituted Derivatives The diphenylamino alcohol 1 reacts with phosphoric acid to yield the fluorene 2 . Whereas 1b cyclises to yield 2b only, 3,3-disubstituted derivatives of 1 should be capable of producing 6, 7 and 8 . In fact, however, only 6 or 7 are formed depending on the nature of the substituents. Compound 3 reacts to yield the fluorene 4 . Ring opening leads to 5 .