Syntheses of Novel Pyridazinomorphinans by Inverse Electron Demand Cycloaddition and their Binding to μ and κ Receptors

A number of novel pyridazinomorphinans have been synthesized by the inverse electron demand Diels-Alder reaction of various 3,6-disubstituted 1,2,4,5-tetrazines with enamines derived from dihydrocodeinone and with codeinone. Reduction of some of the pyridazinomorphinans did not furnish the expected pyrroloepoxymorphinans; in all cases investigated reductive cleavage of the epoxybridge was observed to yield dihydropyridazino- or pyrrolomorphinans. The structures of all new compounds were assigned by the spectral data, that of the cycloadduct of codeinone was additionally verified by X-ray crystallography. Compounds 5a, 8, 11a , and 16 have been evaluated for their affinity at μ and κ opioid receptors in radioligand binding assays. Their ability to inhibit [³H]DAMGO binding at μ and [³H]U 69.593 binding at κ receptors, respectively as compared to codeine has been found to be lower.     

Treatment of iatrogenic biliary obstruction by balloon dilatation of a biliary jejunal fistula

Biliary obstruction and multiple hepatic abscesses occurred in a patient after ligation of a segmental branch of the right hepatic duct. The patient was successfully managed by transhepatic biliary drainage and balloon dilatation of an internal fistula that developed between the ligated duct and a Roux limb of jejunum. Internal biliary fistulas may be dilated using interventioanl radiologic techniques to permit nonobstructed bile flow. Implications for the nonsurgical treatment' of biliary strictures are discussed.     

Asymmetrische elektrophile α-Amidoalkylierung, 4. Mitt.: Erzeugung und Abfangreaktionen chiraler N-Acylpyrrolidiniumionen

Asymmetric Electrophilic α-Amidoalkylation, 4): Generation and Trapping Reactions of Chiral N- Acylpyrrolidiniumions The pyrrole derivatives 1 , 6 , and 10 react in the presence of TiCl₄ with the silyl enol ether 3 to form α-substituted pyrrolidine amides steroselectively. 6 and 10 (after HCl-addition = > 11 ) react even at ?78°C, the reaction of 10 exceeds that of 6 in yield and stereoselectivity.