Synthesis and pharmacological effects of the enantiomers of the N-phenethyl analogues of the ortho and para e- and f-oxide-bridged phenylmorphans

The N-phenethyl analogues of (1R*,4aR*,9aS*)-2-phenethyl-1,3,4,9a-tetrahydro-2H-1,4a-propanobenzofuro[2,3-c]pyridin-6-ol and 8-ol and (1R*,4aR*,9aR*)-2-phenethyl-1,3,4,9a-tetrahydro-2H-1,4a-propanobenzofuro[2.3-c]pyridin-6-ol and 8-ol, the ortho- (43) and para-hydroxy e- (20), and f-oxide-bridged 5-phenylmorphans (53 and 26) were prepared in racemic and enantiomerically pure forms from a common precursor, the quaternary salt 12. Optical resolutions were accomplished by salt formation with suitable enantiomerically pure chiral acids or by preparative HPLC on a chiral support. The N-phenethyl (-)- para-e enantiomer (1S,4aS,9aR-(-)-20) was found to be a mu-opioid agonist with morphine-like antinociceptive activity in a mouse assay. In contrast, the N-phenethyl (-)-ortho-f enantiomer (1R,4aR,9aR-(-)-53) had good affinity for the mu-opioid receptor (K(i) = 7 nM) and was found to be a mu-antagonist both in the [(35)S]GTP-gamma-S assay and in vivo. The molecular structures of these rigid enantiomers were energy minimized with density functional theory at the level B3LYP/6-31G* level, and then overlaid on a known potent mu-agonist. This superposition study suggests that the agonist activity of the oxide-bridged 5-phenylmorphans can be attributed to formation of a seven membered ring that is hypothesized to facilitate a proton transfer from the protonated nitrogen to a proton acceptor in the mu-opioid receptor.     

A novel synthesis of 9-hydroxyaporphine

(±)-N-Methyllaurotetanine (3) was readily prepared $\text{via}$ the $\text{o}$-quinol acetate (2), which was obtained from the 1-(3′-hydroxybenzyl)-tetrahydroisoquinoline (1) by lead tetraacetate oxidation.     

Die Anwendung eines Mehrfach-Detektorsystems zur stereoskopischen Rasterbeobachtung in der Elektronenstrahl-Mikroanalyse

Zusammenfassung Nach einer Übersicht über die Informationsmöglichkeiten der Elektronenstrahlmikroanalyse wird eine neue Methode der stereoskopischen Detektion von der Probenoberfläche rückgestreuter Elektronen dargestellt. An Hand von Beispielen wird gezeigt, daß dadurch eine gute Unterscheidung zwischen Oberflächentopographie und chemischer Zusammensetzung der Gefügebestandteile an der Probenoberfläche möglich ist.

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Summary Following a review of the information possibilities of the electron beam microanalysis, a new method is presented involving the stereoscopic detection of the electrons sprayed back from the surface of the specimen. By means of examples it is shown that in this way it is possible to differentiate well between surface topography and chemical composition of the structural components on the surface of the specimen.

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Résumé Après une vue d'ensemble sur les possibilités d'informations microanalytiques par irradiation électronique, on présente une nouvelle méthode de détection stéréoscopique de la surface des échantillons par diffraction électronique en retour. On montre en se servant d'exemples qu'une bonne distinction entre la topographie superficielle et la composition chimique des constituants de la texture est ainsi possible sur la surface de l'échantillon

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Vortrag anläßlich des Kolloquiums für metallkundliche Analyse mit besonderer Berücksichtigung der Elektronenstrahl-Mikroanalyse, Wien, 22. Oktober 1964.     

Electrochemical evaluation of alternating duplex-triplex conversion effect on the anthraquinone-photoinjected hole transport through DNA duplex immobilized on a gold electrode

Amperometry was employed to characterize the anthraquinone (AQ)-photoinjected hole transport through a 20-mer oligodeoxynucleotide (ODN) duplex, as immobilized on the surface of a gold electrode, and its triplex forms converted by association with several third oligopyrimidine (OPD) short strands. While the cathodic photocurrent was observed upon irradiation at 365 nm of the AQ photosensitizer linked to the end of DNA duplex, a marked lowering of the current density was identified to occur by the triplex formation of a duplex with a given third OPD short strand. The photocurrent through the DNA duplex showed a reversible fall-rise response concomitant with alternating association-dissociation cycle of the OPD short-strand, as regulated by temperature change around the corresponding melting temperature of the DNA triplex. Both the switched photoirradiation and the thermally alternating duplex-triplex conversion could provide tools of regulating the DNA hole transport.     

A new toxic neoanisatin derivative from the pericarps of Illicium majus

A new toxic neoanisatin-derivative (1) was isolated from the pericarps of Illicium majus. The structure of this compound was elucidated by spectroscopic data, including the 2D COSY NMR technique. The toxicity of compound 1 is also described.     

Retinoidal pyrimidinecarboxylic acids. Unexpected diaza-substituent effects in retinobenzoic acids

Several pyridine- and pyrimidine-carboxylic acids were synthesized as ligand candidates for retinoid nuclear receptors, retinoic acid receptors (RARs) and retinoic X receptors (RXRs). Although the pyridine derivatives, 6-[(5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthalenyl)carbamoyl]pyri dine-3-carboxylic acid (2b) and 6-[(5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthalenyl)carboxamido]py ridine-3-carboxylic acid (5b) are more potent than the corresponding benzoic acid-type retinoids, Am80 (2a) and Am580 (5a), the replacement of the benzene ring of Am580 (5a), Am555 (6a), or Am55 (7a) with a pyrimidine ring caused loss of the retinoidal activity both in HL-60 cell differentiation assay and in RAR transactivation assay using COS-1 cells. On the other hand, pyrimidine analogs (PA series, 10 and 11) of potent RXR agonists (retinoid synergists) with a diphenylamine skeleton (DA series, 8 and 9) exhibited potent retinoid synergistic activity in HL-60 cell differentiation assay and activated RXRs. Among the synthesized compounds, 2-[N-n-propyl-N-(5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthalenyl)a mino]pyrimidine-5-carboxylic acid (PA013, 10e) is most active retinoid synergist in HL-60 assay.     

Separation of trans-1,2-cyclohexanediaminetetra-acetic acid chelates of bismuth(III), iron(III) and copper(II) by reversed-phase paired-ion chromatography

Trans-1,2-cyclohexanediaminetetra-acetic acid (DCTA) chelates of bismuth(III), iron(III) and copper(II) have been separated by two techniques using reversed-phase paired-ion chromatography. In one, the chelates in aqueous solution were separated within 20 min on a 6.0 × 300 mm ERC-ODS column with 10⁻²M tetrabutylammonium ion (TBA⁺) in methanoi-water mixture (45:55 v/v) as eluent. In the other, the metal ions in aqueous solution were separated within 10 min by direct injection into an ERC-ODS column with 10⁻²M TBA⁺/10⁻³M DCTA in methanoi-water mixture (40:60 v/v) as eluent.     

Formation of α-Alumina Around 500°C in Alkoxy-Derived Alumina Gels Under Ambient Pressure—Effects of Starting Solution Composition and Seeding

The hydrolysis of aluminum-sec-butoxide (ASB) in the ASB-H₂O-C₂H₅OH-HCl solutions at 0°C for 18 h and subsequent aging of the sol for 30 days at 5°C provided an alumina gel which was partially (20–30 wt%) transformed to -Al₂O₃ when heat-treated at 500°–600°C under ambient pressure. In addition to the hydrolysis and aging conditions, the amounts of water and HCl in the starting solution were found to be very important factors for the low temperature formation of -Al₂O₃ in the resultant gel. Some difference in the chemical environment of involved OH groups was found between the alumina gel forming -Al₂O₃ at 500°–600°C and the conventional gel. Corundum seeding was found to be effective; thus, 1 wt% seeding brought about an increase in the fraction of -Al₂O₃ formed at 600°C to 40–50 wt%.     

Kinetic study of the ClOO + NO reaction using cavity ring-down spectroscopy

Cavity ring-down spectroscopy was used to study the reaction of ClOO with NO in 50-150 Torr total pressure of O2/N2 diluent at 205-243 K. A value of k(ClOO+NO) = (4.5 +/- 0.9) x 10(-11) cm3 molecule(-1) s(-1) at 213 K was determined (quoted uncertainties are two standard deviations). The yield of NO(2) in the ClOO + NO reaction was 0.18 +/- 0.02 at 213 K and 0.15 +/- 0.02 at 223 K. An upper limit of k(ClOO+Cl2) < 3.5 x 10(-14) cm3 molecule(-1) s(-1) was established at 213 K. Results are discussed with respect to the atmospheric chemistry of ClOO and other peroxy radicals.     

Diastereoselective Brook rearrangement-mediated [3+4] annulation: application to a formal synthesis of (+)-laurallene

The formal synthesis of (+)-laurallene, a halogenated eight-membered ring ether, was accomplished. The synthesis involves construction of a trans alpha,alpha'-disubstituted oxocene structure 16 through a Brook rearrangement-mediated [3+4] annulation using acryloylsilane 10 and 6-oxa-2-cycloheptenone 9 and its conversion into 2, which has been transformed into (+)-laurallene by Crimmins and co-workers.