Aldoxime Group Research Articles

Degradation of Three Related Bis(Pyridinium)Aldoximes in Aqueous Solutions at High Concentrations: Examples of Unexpectedly Rapid Amide Group Hydrolysis

The principal initial degradation products of two bis(pyridi- nium)aldoxime organophosphate-inhibited acetylcholinesterase reactivators, 1 (HI-6) and 3 (HS-6), in concentrated nonbuffered aqueous solutions approximating potential therapeutic dosage concentrations were found to be the carboxylic acid derivatives 2 and 4 formed from the hydrolysis of the amide functional group. Compounds 2 and 4 were prepared by heating 1 and 3 in the presence of high concentrations of hydroxylamine hydrochloride and characterized by 1H and 13C NMR, IR, and UV analyses. Estimates of the rates of hydrolysis of the amide groups in 1 and 3 and in model compounds 5, 7, and 8 under similar conditions were determined. The unexpectedly rapid hydrolysis of the amide groups in 1 and 3 was attributed to both the hydrogen ion catalysis of the concentrated aqueous solutions of the unusually acidic bis(pyridinium)aldoximes 1 and 3 and general acid catalysis by the aldoxime group.

1-substituted-1,2,5,6-tetrahydropyridine-3-carboxaldehyde-O-alkyloximes as novel orally active and long-lasting muscarinic cholinergic agonists

Our previous attempts to design muscarinic agonists related to arecoline with the prerequisites for clinical use were successful with the discovery of 1,2,5,6-tetrahydropyridine-3-carboxaldehyde-O-methyloxime hydrochloride, RU 35963, and structurally related compounds, in which the metabolically labile ester group of arecoline was replaced with the bioisosteric and stable aldoxime group. With the aim of obtaining compounds with improved cholinomimetic properties, several aryl- and alkyl-carbamates of RU 35963, as well as O-alkyl-, and O-aryl-carbamates of the 1-hydroxy-1,2,5,6-tetrahydropyridine-3-carboxaldehyde-O-methyloxime hydrochloride, 24, have been synthesized and evaluated biologically. The most interesting molecules to emerge from the primary screening have been evaluated more extensively and their cholinomimetic profiles compared with those of the parent molecules. In vitro studies indicate that none of these prodrugs have affinity for muscarinic receptor sites and some of them (aryl-carbamates) have cholinesterase inhibiting properties. Results from in vivo experiments in mice and rats showed that these new substances, 1-[4-chlorophenyl] oxycarbonyl-1,2,5,6-tetrahydropyridine-3- carboxaldehyde-O-methyloxime ( 16 = RU 47213) in particular, have cholinomimetic properties that compare favourably with those of the parent compounds. After oral administration 16 was clearly superior to RU 35963 in terms of central selectivity, duration of action and therapeutic indexes.

Syntheses of methyl 6-deoxy-6-hydroxyamino-α- d-glucopyranoside, 6′- N-hydroxykanamycin A, and 6′- N-hydroxydibekacin

Methyl 6-deoxy-6-hydroxyamino-α- d-glucopyranoside has been prepared from methyl 6-amino-6-deoxy-α- d-glucopyranoside via oxidation with hydrogen peroxide in the presence of sodium tungstate [to give the corresponding 6-aldoxime ( 2)], followed by reduction with sodium cyanoborohydride in an acidic medium. Acetylation of the Z isomer of 2 gave a nitrile derivative. The above oxidation-reduction procedure was applied to kanamycin A and dibekacin, starting from the corresponding 6′-amino- N-tosyl derivatives. On treatment with sodium in liquid ammonia, 6′-deamino-6′-hydroxyimino-1,3,3″-tri- N-tosylkanamycin A gave the corresponding N-detosyl derivative in good yield with the 6′-aldoxime group remaining intact, but, with 6′-deamino-6′-hydroxyimino-1,3,2′,3″-tetra- N-tosyldibekacin, the N-detosyl derivative ( 17) was obtained only by a very short reaction period. The antibacterial activities of 17 and 6′- N-hydroxydibekacin were demonstrated.

Syntheses of functional condensation polymer. I. Polyesters having pendant functional groups such as hydroxyl, formyl, aldoxime, aminomethyl and hydroxymethyl

AbstractUnsaturated polyesters having pendant functional groups such as hydroxyl, formyl, aldoxime, aminomethyl and hydroxymethyl, have been prepared and characterized, and some of their properties were investigated. Reaction conditions for the epoxidation of unsaturated polyesters and hydrolysis of the epoxy groups in the polyesters were established to control the amount of pendant diol groups. It was possible to incorporate up to 90 mole‐% of formyl side groups into the unsaturated polyester by the hydroformylation with the rhodium catalyst. In addition, the formyl side groups of the modified polyester were converted into hydroxymethyl or aldoxime groups and were then converted to amino groups. The melting points of the modified polyesters decreased with increasing the pendant group content of the polyesters, as expected. Aliphatic polyesters having pendant hydroxyl or amino groups had a high affinity for moisture, which might be ascribed to the participation of the hydrophilic pendant groups in the modified polyesters.