ABSTRACT
Oripavine was isolated from the dried capsules of a variety of PAPAVER SOMNIFERUM cultivated on Tasmania.
ABSTRACT
Substituted benzoic acid esters of 1-methyl-4-piperidinol showed analgesic activity when assayed by the mouse hot-plate methods, the more potent ones falling in the morphine-codeine range. To understand how substituents on the aromatic ring affect the analgesic potency, quantitative structure-activity correlations were carried out on a series of 44 derivatives. Among the various substituent parameters included in the study, Lortho (Length of ortho-substituents) and B1 (minimal width of substituents) or E8 at meta and para positions gave negative correlation with the potency, while lipophilicity (especially pi meta) and the ability of being a hydrogen-bond acceptor enhanced the potency. Based on the QSAR results, a substitution pattern of the phenyl group was defined for optimal activity. Implications on drug-receptor interactions and the possible binding mode of these compounds were discussed.
Subject(s)
Analgesics/chemical synthesis , Piperidines/chemical synthesis , Animals , Chemical Phenomena , Chemistry, Physical , Hydrogen Bonding , Meperidine/pharmacology , Mice , Molecular Conformation , Morphine/pharmacology , Piperidines/pharmacology , Reaction Time/drug effects , Structure-Activity RelationshipSubject(s)
Alkaloids/biosynthesis , Papaver/chemistry , Papaverine/analogs & derivatives , Plants, Medicinal/chemistry , Thebaine/analogs & derivatives , Alkaloids/chemistry , Molecular Structure , Papaverine/biosynthesis , Papaverine/chemistry , Thebaine/chemistry , Thebaine/isolation & purificationABSTRACT
The unnatural thebaine analog, oripavine 3-ethyl ether, was efficiently metabolized to morphine 3-ethyl ether and morphine in the opium poppy. An attempt to detect oripavine hy an isotope dilution experiment based on its presumed biosynthesis from reticuline was unsuccessful.
Subject(s)
Papaver/chemistry , Papaverine , Plants, Medicinal/chemistry , Molecular Structure , Papaver/metabolism , Papaverine/analogs & derivatives , Papaverine/biosynthesis , Papaverine/chemistryABSTRACT
Administration of 1-3H-N-methyl-14C-(+/-)-reticuline to Papaver bracteatum gave good incorporation of carbon-14 into thebaine and a decrease in the tritium to carbon-14 ratio indicative of racemization. The incorporation of carbon-14 and the extent of tritium loss were the same whether reticuline was administered to the intact plant or to isolated leaves. Carrier dilution with cold codeine, codeinone, and morphine showed only insignificant incorporation of radioactivity into codeine and none at all into codeinone and morphine. When codeinone was administered to the living plant, it was converted to codeine rapidly and efficiently, but no O-demethylation to morphine could be detected. The experimental data indicate that the biosynthesis of thebaine in P. bracteatum proceeds by the same pathway as in the opium poppy. The limiting step in the sequence is the demethylation of the enol ether group of thebaine to neopinone.
Subject(s)
Morphine Derivatives/biosynthesis , Papaver/metabolism , Plants, Medicinal , Codeine/analogs & derivatives , Codeine/metabolism , Morphine Derivatives/isolation & purification , Papaver/anatomy & histology , Reticulin/metabolism , Thebaine/metabolismSubject(s)
Pilocarpine/biosynthesis , Chemical Phenomena , Chemistry , Methylation , Plants, Medicinal/metabolismABSTRACT
A protoberberine alkaloid was isolated from opium and characterized as (-) 2, 10-dihydroxy-3,9-dimethoxytetrahydroprotoberberine by spectroscopic methods and by comparison with (-) stepholidine.