R. Haller

Interactions of some parasympatholytics and structurally related drugs with acetylcholinesterases: Kinetics studies

Abstract The interactions of the parasympatholytics adiphenine, adiphenine H, propantheline and the structurally related compounds diphenhydramine, D -propoxyphene and methadone with acetylcholinesterases were studied by means of kinetic measurements. Acetylcholinesterase (AChE) was used as membrane-bound enzyme from bovine red cells and in a solubilized form from Electrophorus electricus . All the drugs studied are inhibitors of AChE. Differences between the membrane bound and the solubilized form can be deduced from different inhibitory mechanisms. A mixed competitive-non-competitive mechanism is characteristic for the membrane-bound enzyme, while a predominantly non-competitive mechanism is involved in the case of the solubilized enzyme. The negative cooperative behaviour of AChE is not changed by these inhibitors. A “two-site” hypothesis for the binding of the investigated drugs is proposed.

Zur Synthese epimerer Alkohole aus heterocyclischen β-Ketodicarbonsäureestern

Die Umsetzung heterocyclischer β‐Ketodicarbonsäureester, welche Schwefel, Sauerstoff oder Stickstoff als Ringglied enthalten, mit Natriumborhydrid führt zur Bildung jeweils zweier epimerer Alkohole. Das Epimerenverhältnis ist stark von der Art des Lösungsmittels abhängig, in welchem die Reduktion durchgeführt wird. Die als konjugierte Chelate stabilisierten Enolformen werden durch NaBH4 nicht angegriffen.

Stereochemistry of substituted isomeric 3-oxa-7-aza-bicyclo[3.3.1]nonan-9-ones

Abstract Two isomers of 7-methyl-9-oxo-2,4-diphenyl-3-oxa-7-aza-bicyclo[3.3.1]nonan-1,5-ethyl dicarboxylate (1a and 1b) were obtained by condensation of 2,6-diphenyl-1-oxa-4-oxo-cyclohexan-3,5-ethyl dicarboxylate with methylamine and formaldehyde. Their crystal structures were determined by X-ray diffraction. They crystallize in the triclinic space group P1̄ with (for 1a) a = 12.907(5), b = 11.223(4), c = 8.993(4) Å, α = 105.82(4), β = 100.14(5), γ = 97.35(4)°, and (for 1b) a = 16.400(7), b = 13.062(4), c = 11.336(2) Å, α = 94.19(3), β = 94.74(3), γ = 102.56(4)°. This investigation has shown that isomer 1a has the boat-chair conformation, and isomer 1b has the chair-chair conformation. The formation of la causes a configurational change of the phenyl substituents. The two species are characterized by NMR spectroscopy. - Another comparable bicyclononanone with a bulky substituent at the nitrogen atom has been synthesized and was investigated spectroscopically. This compound should have chair-boat conformation (with the boat conformation in the N-heterocyclic ring) whereas 1a has the boat conformation in the O-heterocyclic ring.