N-Glykoside und Glykamine von Cyclopentylamin, 1.2.3.4-Tetrahydro-1-naphthylamin und 5α-Cholestan-3β-amin

N-Glycosides and Glycamines of Cyclopentylamine, 1,2,3,4-Tetrahydro-1-naphthylamine and 5α-Cholestan-3β-amine The galactosyl-, mannosyl- and lactosyl-N-glycosides of cyclopentylamine and the galactosyl- and glucosyl-N-glycosides of the other two title compounds are described. All N-glycosides are reduced by cyanoborohydride to the corresponding glycamines.     

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.     

Neue Reaktionen an Phthalidisochinolinalkaloiden. Alkoxytauschreaktionen und Isomerisierungen an α- und β-Narcotin

New Reactions of Phthalidoisoquinoline Alkaloids. Alkoxy Exchange Reactions and Isomerisations of α- and β-Narcotine Substitution of the 7-methoxy group in α- and β-narcotine by other alkoxy groups occurs in an anhydrous ROH/RONa system. It is accompanied by isomerisation in position 3 with preference for the α-configuration (5R, 3S). In an alkaline aqueous system (ROH/KOH or 1N KOH only isomerisation in position 3 with preference for the β-configuration (5R, 3R) was observed. Some of the new 7-alkoxynarcotines were evaluated for their antitussive activity.     

α-Thiotetronsäuren, 1. Mitt.: Synthese und Eigenschaften von γ-Alkyliden-α-thiotetronsäuren

α-Thiotetronic Acids, I: Synthesis and Properties of γ-Alkylidene α-Thiotetronic Acids We report on the synthesis of the alkylidene α-thiotetronic acids 11 and 12a and a variety of their derivatives, starting with 2,3-dimethoxysuccinic thioanhydride ( 4 ) or diethyl 3-thioxoglutarate. The rhodium(II)-catalysed decomposition of the diazoketone 26 furnishes the reductone 12p and the aminoreductone 12r with the thietanone 27 as one of the by-products.     

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.     

Massenspektrometrie einiger substituierter α-Ethoxy-Pyridine und -Pyrimidine

Mass Spectrometry of Substituted α-Ethoxypyridines and -Pyrimidines The molecular ions of the α-ethoxy heterocycles 1–8 lose * CH₃ and C₂H₄ or * C₂H₅ from the α-ethoxy group. Also, fragmentation of the esters 2b, 3b, 4–8 occurs by degradation of the ethoxycarbonyl group.     

Bis-thiolurethane aus α,ω-Alkandithiolen und Isocyanaten

Biscarbamothioates from α,ω-Alkanedithiols and Isocyanates Sixty biscarbamothioates 1 were prepared by triton-B catalyzed addition of α,ω-alkanedithiols to isocyanates. Some of the products were investigated for biological activity.     

Darstellung und Reaktivität von α-Acyloxy-N-acylglycin-Derivaten

Synthesis and Reactivity of Derivatives of α-Acyloxy-N-acylglycine The N,O-Acylals 5–15 are obtainable from the chloro compounds 2 and carboxylic acids. Treatment of the electrophilic synthons with nucleophiles under basic conditions leads to products 16–19 by way of transamidoalkylation. A mechanism of the reaction is proposed.     

Synthesen und Ringverengungsreaktionen α-halogenierter N-Phenylcamphersäureimide

Syntheses and Ringcontractions of β-Halo N-Phenylcamphoric Acid Imides By deprotonation and addition of electrophiles the N-phenylcamphoric acid imide 8 is transformed to the halo derivatives 3a–3c and to the deuterium labeled imide 3d . Under basic conditions 3b rearranges with ringcontraction to yield the bicyclic imido lacton 9a as a major product, whereas the regioisomer 4 is formed only in minor amounts.     

Pharmacological characterization of A-131701, a novel α1-adrenoceptor antagonist selective for α1A- and α1D-compared to α1B-adrenoceptors

New compounds selective for α_1A-adrenoceptors in the prostate may offer enhanced efficacy for benign prostatic hyperplasia (BPH), with fewer side effects than current treatment. A-131701 (3-[2-((3aR,9bR)-cis-6-methoxy-2,3,3a,4,5,9b,hexahydro-[1H]-benz[e]isoindol-2-yl)ethyl]pyrido[3′,4′:4,5]thieno [3,2-d]pyrimidine-2,4(1H,3H)-dione), from a novel class of benz[e]isolindole pyridothienopyrimidines and pyridothienopyrazines, is selective for α_1a- and α_1d-adrenoceptors in radioligand binding studies (0.22 nM at α_1a-, 0.97 nM at α_1d-) compared to α_1b-sites (2.5 nM) and in isolated tissue bioassays (pA₂ values of 8.9–9.0 for α_1A-receptors in rat vas deferens or canine prostate strips, 9.1 at α_1D-sites (rat aorta)), compared to 7.9 at α_1B-sites (rat spleen). A-131701 also potently blocked radioligand binding to α₁-adrenoceptors in canine and human prostatic membranes, but was considerably weaker at α₂-adrenoceptors. In isoflurane-anesthetized dogs, A-131701 antagonized epinephrine-induced increases in intraurethral pressure (IUP) with a pseudo-pA₂ value of 8.17. In spontaneously hypertensive rats, A-131701 caused transient decreases in mean arterial blood pressure (MABP) and transient tachycardia. The area under the curve (AUC₀→₆₀ min) for the hypotensive response was dose-related, with a log index value for A-131701 of 5.33, suggesting a selectivity of >600-fold comparing IUP to MABP effects. In pentobarbital-anesthetized dogs, A-131701 was more potent in blocking phenylephrine (PHE)-induced increases in IUP (pseudo-pA₂ = 8.0) compared to concurrently measured MABP (pseudo-pA₂ = 7.2), or sixfold selective. Doses greater than 1,000 nmol/kg i.v. of A-131701 were required to lower blood pressure by 10 mm Hg in these dogs (pED₁₀ =. 5.57), indicating a uroselectivity ratio of >250, superior to doxazosin, terazosin, or tamsulosin. Thus, A-131701 is selective for α_1A- and α_1D- vs. α_1B-adrenoceptors in vitro, and prostatic function vs. blood pressure effects in vivo, which may provide therapeutic advantages in the treatment of BPH. Drug Dev. Res. 44:140–162, 1998. © 1998 Wiley-Liss, Inc.     

Synthesis of [3α‐3H] 17α‐Hydroxy pregnenolone and [3α‐3H] Pregnenolone

For the first time, [3α‐³H] 17α‐hydroxy pregnenolone (1) was synthesized through a multiple step sequence. The presence of [3β‐³H] isomer in RP‐HPLC purified product was identified by tritium NMR. The [3β‐³H] isomer was then separated from [3α‐³H] 17α‐hydroxy pregnenolone with chiralPAK AD‐H column. [3α‐³H] pregnenolone (2) was synthesized from commercial available 5‐pregnen‐3,20‐dione in one step with an improved procedure.     

Struktur-Wirkungs-Beziehungen bei Histaminanaloga, 23. Mitt. Absolute Konfiguration und histaminartige Wirkung der enantiomeren α-Chlormethylhistamine und Nα-Methyl-α-chlormethylhistamine

Structure-Activity Relationships of Histamine Analogues, XXIII: Absolute Configuration and Histamine-like Activity of the Enantiomeric α-Chloromethylhistamines and Nα-Methyl-α-chloromethylhistamines The histamine-like activities of the enantiomeric α-chloromethylhistamines (+)- 2a and (?)- 2a and of the Nα-methyl-α-chloromethylhistamines (+)- 2b and (?)- 2b on the guinea pig ileum (H₁) and atrium (H₂) are reported. The absolute configurations of the enantiomers were determined.     

Über β-Chlor- und β-Mesyl-äthylhydrazine

β-Chloro- and β-Mesylethyl Hydrazines From benzaldehyde-β-hydroxyethyl-hydrazone hydrochloride ( 6 ) with thionyl chloride the benzaldehyde-β-chloroethyl-hydrazone hydrochloride ( 7 ) is formed. This gives upon hydrolysis with dilute hydrochloric acid the β-chloroethyl-hydrazine dihydrochloride ( 5 ). – Methylhydrazine and 1,2-dichloroethane undergo reaction at room temperature to methylhydrazine hydrochloride ( 10 ) and N-methyl-N-β-chloroethyl-hydrazine ( 9 ), which can be isolated as dihydrochloride 12 . – Benzaldehyde-β-hydroxyethyl-hydrazone ( 6 ) forms with mesyl chloride the benzaldehyde-(N-methylsulfonyl)-N-β-mesylethyl-hydrazone ( 14a ) which can be hydrolyzed with dilute hydrochloric acid to the N-β-mesylethyl-methanesulfonic hydrazide ( 15 ).     

Conformational investigation of αβ-dehydropeptides

Solution conformations of three series of model peptides, homochiral Ac-Pro-L-Xaa-NHCH₃ and heterochiral Ac-Pro-D-Xaa-NHcH₃ (Xaa = Val, Phe, Leu, Abu. Ah) as well as αβ-unsaturated Ac-Pro-ΔXaa-NHCH₃ [Δ Xaa =ΔVal, (Z)-ΔPhe, (Z)-ΔLeu, (Z)-ΔAbu] were investigated in CDCl₃ and CH₂Cl₂ by ¹H-, ¹³C-NMR, and FTIR spectroscopy. NH stretching absorption spectra, solvent shifts Δδ for NH (Xaa) and NHCH₃ on going from CDCl₃ to (CD₃)₂SO, diagnostic interresidue proton NOEs, and trans-cis isomer ratios were examined. These studies performed showed the essential difference in conformational propensities between homochiral peptides (L-Xaa) on the one hand and heterochiral (D-Xaa) and αβ-dehydropeptides (ΔXaa) on the other. Former compounds are conformationally flexible with an inverse γ-bend, a β-turn, and open forms in an equilibrium depending on the nature of the Xaa side chain. Conformational preferences of heterochiral and αβ-dehydropeptides are very similar, with the type-II β-turn as the dominating structure. There is no apparent correlation between conformational properties and the nature of the Xaa side chain within the two groups. The β-turn formation propensity seems to be somewhat greater in αβ-unsaturated than in heterochiral peptides, but an estimation of β-folded conformers is risky.     

Reaktionen α,β-ungesättigter γ-Oxosulfone mit Nucleophilen

Reactions of α,β-Unsaturated γ-Oxosulfones with Nucleophiles Bromination of the γ-oxosulfones 1 and subsequent dehydrohalogenation leads to the α,β-unsaturated γ-oxosulfones 3 . These products react with primary and secondary amines to yield the enaminoketones 7 . γ-Oxobissulfones 10 are formed from 3 by addition of the sulfinic acids 9 . Thioles 11 react with 3 to give the γ-oxomercaptosulfones 12 or the thioacetals 14 .