Lactone, 11. Mitt. Synthese von 4.9-Dihydropyrano[3.4-b]indol-1(3H)-onen aus α-Ethoxalyl-γ-lactonen

Lactones, XI: Syntheses of 4.9-Dihydropyrano[3.4-b]-indol-1(3H)-ones from α-Ethoxalyl-γ-lactones Cleavage and decarboxylation of the α-ethoxalyl-γ-lactones 1a-d followed by treatment with phenylhy-drazines yield the hydrazones 4a-l , which can be rearranged to the indololactones 5a-m. Starting from the δ-lactones 6 and 10 , the same reactions lead to indoles without lactone ring closure.     

Lactone, 1. Mitt. Synthese dihydroxylierter Diphenylethylamine über α-Amino-γ-lactone

Lactones, I: Synthesis of Dihydroxylated Diphenylethanamines via α-Amino-γ-lactones Treatment of α-amino-γ-lactones with phenyllithium yields the 2-amino-1,1-diphenylalkane-1,4-diols 2a–f which can be classified as dihydroxylated diphenylethanamines.     

Lactone, 3. Mitt.1) Zur Synthese von α-Aminoalkyl-γ-lactonen

Lactones, III: Synthesis of α-Aminoalkyl-β-lactones Alkylation of α-acetyl-β-lactones with α-aminoethyl and -propyl chlorides, followed by in situ cleavage of the acetyl group with an excess of ethanolate is a general synthetic route to α-aminoethyl- and α-aminopropyl-β-lactones. The yields are limited by side reactions.     

Lactone, 16. Mitt.: Synthese von 4,9-Dihydropyrano[3,4-b]indol-1(3H)-onen aus α-Ethoxalyl-δ-valerolacton

Lactones, XVI: Synthesis of 4,9-Dihydropyrano[3,4-b]indol-1(3H)-ones from α-Ethoxalyl-δ-valerolactone Treatment of α-ethoxalyl-δ-valerolactone (1) with diazotized anilines and indolization of the intermediate hydrazones 4 leads to the pyranoindolones 5 . Compared to the recently reported reaction of α-ethoxalyl-γ-butyrolactone with arylhydrazines²⁾, this synthesis is more versatile with regard to variation of substituents at the aromatic ring. Stereochemistry and reactivity of the α-arylhydrazonolactones are discussed.     

Synthese von α-Trihalogenmethyl-γ-oxosulfonen

Synthesis of β-Trihalogenomethyl-γ-oxosulfones The title-compounds 6 are formed by reaction of sulfinic acids 4 with 1,1,1-trihalogen-2-buten-4-ones 1 and 1,1,1-trihalogen-2-chloro-4-butanones 8 , respectively, or by addition of thioles 3 to 1 and subsequent oxidation.     

Synthese von γ,γ'-Dihydroxysulfonen und γ-Hydroxy-γ'-ketosulfonen

Syntheses of γ,γ'-Dihydroxysulfones and γ-Hydroxy-γ'-ketosulfones Reduction of γ,γ'-diketosulfones 1 with dimethylaminoborane leads to γ,γ'-dihydroxysulfones 3 via γ-hydroxy-γ'-ketosulfones 2 . The influence of substituents on the ratio of the yields of 2 and 3 is investigated.     

Massenspektrometrische Untersuchungen an isomeren α,β- und β, γ-ungesättigten Ketonen mit raumerfüllenden Substituenten

A Mass Spectrometric Study on Isomeric α,β- and β,γ-Unsaturated Ketones with Bulky Substituents The mass spectra of the α,β- and β,γ-unsaturated ketones 1-4 (scheme 1) are very different depending on the stereochemistry of the double bond. The E-configurated ketone 2 predominantly shows McLafferty fragmentation, whereas Z-configurated ketone 1 reveals ?-cleavage. In the β, γ-unsaturated ketones 3 and 4, mainly loss of the pertinent allyl radical by α-cleavage was observed.     

Lactone, 10. Mitt. Zur Synthese N-heterocyclisch substituierter γ,γ-Diphenyl-γ-butyrolactone

Lactones, X: Synthesis of γ,γ-Diphenyl-γ-butyrolactones Substituted by N-Heterocycles Starting from 3 and 16 , syntheses of γ,γ-diphenyl-γ-butyrolactones with N-heterocycles at the α-position are described. Scope and limitation of the syntheses, tautomerism and stereochemistry of the products as well as spectroscopic results which are inconsistent with data from the literature are discussed.     

Lactone, 4. Mitt. Synthese dihydroxylierter Diphenylalkylamine über Aminoalkyl-γ-lactone

Lactones, IV: Synthesis of Dihydroxylated Diphenylalkanamines via Aminoalkyl-γ-lactones Excess of phenyllithium reacts with the aminoalkyl-γ-lactones 1 – 3 , 10 , 13 to yield the 1,1-diphenyl-propan- 4 , -butan- 5 , and -pentanamines 6 , 14 . The reaction can be considered as a general method for the synthesis of dihydroxylated 1,1-diphenylalkanamines, which is limited only by the poor crystallizability of the end products.     

Molluskizid wirksame Spiro-α-methylen-γ-butyrolactone

α-Methylene-γ-butyrolactones with Molluscicidal Activity The α-methylene-γ-butyrolactones 1-28 were tested in vitro for molluscicidal activity against Biomphalaria glabrata. The racemic compound 25 shows the best activity. The synthesis was carried out by modified Reformatzky reaction of the corresponding carbonyl compounds and bromomethylacrylic acid ethyl ester. 7-10, 17 and 22-27 have been synthesized for the first time.     

Stereochemie der Reformatsky-Reaktion von 2-Alkylcyclohexanonen mit α-Brommethylacrylsäureethylester

Stereochemistry of the Reformatsky Reaction of 2-Alkylcyclohexanones with Ethyl α-(Bromomethyl)acrylate A relation between the chemical shifts of the ¹³C-NMR signals of the carbon atoms 4, 5 and 9 and the conformation of the lactone oxygen was found for spiro-α-methylene-γ-butyrolactones prepared by the Reformatsky reaction of 2-alkylcyclohexanones with ethyl α-(bromomethyl)acrylate. It was confirmed by CD measurements on the pyrazoline derivative of one of the lactones. From the structures of the reaction products it was deduced, that trans addition (relative to the substituent at position 2) of the organometallic reagent is prefered.     

Synthese von 2-Oxo-5H-furanen unter Wittig-Horner Bedingungen

Synthesis of 2,5-Dihydro-furan-2-ones under Wittig-Horner Conditions Syntheses under Wittig-Horner conditions are described of the 2,5-dihydrofuran-2-ones 3a-e and 7a-e from the α-hydroxy-oxo compounds 1a, b and the α-halogeno-oxo compounds 5a-e , on the one hand, and the α-phosphonocarboxylates 2a-c , α-phosphonocarboxylic acids 4a, b and potassium α-phosphonocarboxylates 6a, b on the other.     

Ungesättigte und halogenierte γ-Hydroxysulfone; Darstellung und Reaktivität

Unsaturated and Halogenated γ-Hydroxysulfones: Syntheses and Reactivities α,β-Unsaturated γ-hydroxysulfones 2 and β-bromo-γ-hydroxysulfones 4 are prepared from the corresponding keto derivatives by reduction with dimethylaminoborane. Addition of p-toluenethiol to the double bond of 2 takes place in the position β to that of the sulfonyl group. With bases an isomerisation of 2 to γ-ketosulfones 10 is observed. With primary or secondary amines Mannich bases are formed. β-Bromo-γ-hydroxysulfones 4 are cleaved by bases to yield 2 .     

Untersuchungen an 1,3-Thiazinen, 16. Mitt. 4-Oxo-2-thioxo-tetrahydro-1,3-thiazine aus β-Propiolactonen,Teil 2

1,3-Thiazines, XVI: 2-Thioxotetrahydro-1,3-thiazin-4-ones by Use of β-Propiolactones, Part 2 Reactions of β-lactones with dithiocarbamates leading to 2 and cyclization of the products yielding 2-thioxo-tetrahydro-1,3-thiazin-4-ones 3 are described. With derivatives of diketene (β-propiolactones with exocyclic double bonds) no 1,3-thiazines 6 are obtained. Instead, the amides of β-ketoacids 7 are formed with the elimination of carbon disulfide.     

α-Alkylmercapto- und α-Arylmercapto-alkylisocyanate

α-Alkylmercapto- and α-Arylmercapto-alkylisocyanates α-Alkylmercapto- and α-arylmercapto-alkylisocyanates 2 were prepared from α-halosulfides 1 by reaction with silver cyanate. With ammonia, primary or secondary amines they give the corresponding α-mercaptoalkyl-ureas 4 ; with alcohols, the α-mercaptoalkylurethans 3.     

Synthesis of N-(4-aminobenzoyl)-γ-oligo (L-glutamic acid)s*

N-(4-aminobenzoyl)-γ-oligo (l -glutamic acid)s (6) containing from two to six glutamic residues have been prepared in solution using Nα-Boc-α-Bzl protections and isobutyl-chlorocarbonate activation. Key steps in the synthesis were the coupling of γ-oligo(α-benzyl l -glutamate) benzyl esters (1) with N-(4-benzyl-oxycarbonylaminobenzoyl)-l -glutamic acid α-benzyl ester (4) to blocked precursors of N-(4-aminobenzoyl)-γ-oligo (l -glutamic acid)s (5) and catalytic hydrogenolysis of 5 to 6. Elaboration of the required oligo γ-l -glutamate chains (1) was achieved step by step beginning with the coupling of glutamic acid dibenzylester with N-(t-butoxycarbonyl)-l -glutamic acid α-benzyl ester (2) to 3 followed by selective removal of the Boc from 3 with HCl-dioxane followed by coupling with 2.     

Lactone, 23. Mitt.: Synthese und Stereochemie „γ-lactonisierter”︁ Neuroleptika vom Butyrophenon-Typ

Lactones, XXIII: Synthesis and Stereochemistry of ?γ-Lactonized”? Butyrophenone-type Neuroleptics ?γ-Lactonized”? neuroleptics ( 1,2a-c ) can be obtained by reaction of α-formyl, α-carboxy- and α-methylene-lactones 5-7a,b with amines 8a - c . 6a, 1a-c were cis/trans-mixtures with predominating cis-compounds, 6b, 2a cis/trans-mixtures with predominating trans-compounds and 2b , c were isolated as pure trans-isomeres.     

Synthese von 3-methylendisubstituierten 2-Oxo-tetrahydrofuranen und ihre Umlagerung zu den 5,6-Dihydro-2H-pyran-2-onen

Synthesis of 3-Methylene-2-oxotetrahydrofurans and their Rearrangement to 5,6-Dihydro-2H-pyran-2-ones . The synthesis of the 3-methylene-2-oxotetrahydrofurans 5a–g and 6–8 from the α-ketolactons 1a,b by Knoevenagel reaction with 2a–f, 3 and 4 in the presence of TiCl₄/pyridine, piperidine acetate/β-alanine and β-alanine is described. Ring opening and hydrolysis of 5a–d, 5f and 6 gives the 5,6-dihydro-2H-pyran-2-ones 9a–f .     

Agonist function of the recombinant α4β3δ GABAA receptor is dependent on the human and rat variants of the α4‐subunit

1. It is known that the α₄‐subunit is likely to occur in the brain predominantly in α₄β₃δ receptors at extrasynaptic sites. Recent studies have revealed that the α₁‐, α₄‐, γ₂‐ and δ‐subunits may colocalize extrasynaptically in dentate granule cells of the hippocampus. In the present study, we characterized a series of recombinant GABA_A receptors containing human (H) and rat (R) α₁/α₄‐, β₂/β₃‐ and γ_2S/δ‐subunits in Xenopus oocytes using the two‐electrode voltage‐clamp technique. 2. Both Hα₁β₃δ and Hα₄β₃γ_2S receptors were sensitive to activation by GABA and pentobarbital. Contrary to earlier findings that the α₄β₃δ combination was more sensitive to agonist action than the α₄β₃γ_2S receptor, we observed extremely small GABA‐ and pentobarbital‐activated currents at the wild‐type Hα₄β₃δ receptor. However, GABA and pentobarbital activated the wild‐type Rα₄β₃δ receptor with high potency (EC₅₀ = 0.5 ± 0.7 and 294 ± 5 μmol/L, respectively). 3. Substituting the Hα₄ subunit with Rα₄ conferred a significant increase in activation on the GABA and pentobarbital site in terms of reduced EC₅₀ and increased I_max. When the Hα₄ subunit was combined with the Rβ₃ and Rδ subunit in a heteropentameric form, the amplitude of GABA‐ and pentobarbital‐activated currents increased significantly compared with the wild‐type Hα₄β₃δ receptor. 4. Thus, the results indicate that the Rα₄β₃δ, Hα₁β₃δ and Hα₄β₃γ_2S combinations may contribute to functions of extrasynaptic GABA_A receptors. The presence of the Rα₄ subunit at recombinant GABA_A receptors containing the δ‐subunit is a strong determinant of agonist action. The recombinant Hα₄β₃δ receptor is a less sensitive subunit composition in terms of agonist activation.     

Cer(IV)-Oxidationen von β-Aminoketonen. 3. Mitt.: Ein Syntheseweg zu 4-spirosubstituierten 1,2,3,4-Tetrahydroisochinolinen

Cerium(IV) Oxidations of β-Aminoketones. Part III: A Pathway to 4-Spiro-Substituted 1,2,3,4-Tetrahydroisoquinolines Substituted 2′-methyl-2′,3′-dihydro-1′H-spiro[cycloalkan-1,4′-isoquinolin]-2-ones and -[chroman-3,4′-isoquinolin]-4-ones are synthesized by cerium(IV) oxidation of (N-benzyl-N-methylamino)methylcycloalkan-1-ones or corresponding substituted chromanones.