Chiral separation of norlaudanosoline, laudanosoline, laudanosine, chlorthalidone, and three benzoin derivatives using amino acid based molecular micelles.

In this study, 18 polymeric single amino acid and dipeptide surfactants are examined, and their performances, in terms of enantioselectivity, are compared for norlaudanosoline, laudanosoline, laudanosine, chlorthalidone, benzoin, benzoin methyl, and benzoin ethyl enantiomers. Several aspects of amino acid-based polymeric surfactants including comparison of single amino acid versus dipeptide, amino acid order, steric effect, and effect of the position of the chiral center of dipeptide surfactants on the chiral selectivity of these optically active compounds are discussed.

Endogenous formation of morphine in human cells.

Morphine is a plant (opium poppy)-derived alkaloid and one of the strongest known analgesic compounds. Studies from several laboratories have suggested that animal and human tissue or fluids contain trace amounts of morphine. Its origin in mammals has been believed to be of dietary origin. Here, we address the question of whether morphine is of endogenous origin or derived from exogenous sources. Benzylisoquinoline alkaloids present in human neuroblastoma cells (SH-SY5Y) and human pancreas carcinoma cells (DAN-G) were identified by GC/tandem MS (MS/MS) as norlaudanosoline (DAN-G), reticuline (DAN-G and SH-SY5Y), and morphine (10 nM, SH-SY5Y). The stereochemistry of reticuline was determined to be 1-(S). Growth of the SH-SY5Y cell line in the presence of (18)O(2) led to the [(18)O]-labeled morphine that had the molecular weight 4 mass units higher than if grown in (16)O(2), indicating the presence of two atoms of (18)O per molecule of morphine. Growth of DAN-G cells in an (18)O(2) atmosphere yielded norlaudanosoline and (S)-reticuline, both labeled at only two of the four oxygen atoms. This result clearly demonstrates that all three alkaloids are of biosynthetic origin and suggests that norlaudanosoline and (S)-reticuline are endogenous precursors of morphine. Feeding of [ring-(13)C(6)]-tyramine, [1-(13)C, N-(13)CH(3)]-(S)-reticuline and [N-CD(3)]-thebaine to the neuroblastoma cells led each to the position-specific labeling of morphine, as established by GC/MS/MS. Without doubt, human cells can produce the alkaloid morphine. The studies presented here serve as a platform for the exploration of the function of "endogenous morphine" in the neurosciences and immunosciences.

Chromatographic separation and spectrometric identification of the oxidation products from a tetrahydro-isoquinoline alkaloid.

The oxidation chemistry of 3',4'-deoxynorlaudanosoline carboxylic acid, a tetrahydroisoquinoline alkaloid, has been studied by electrochemical approaches. Four reaction products were isolated by semi-preparative high performance liquid chromatography and identified structurally by nuclear magnetic resonance, mass spectrometry, ultraviolet-visible spectrophotometry and electrochemistry studies. An oxidation mechanism was proposed.

Enantio-selective occurrence of (S)-tetrahydropapaveroline in human brain.

Tetrahydropapaveroline is an endogenous complex alkaloid derived from dopamine through the oxidation by monoamine oxidase. This alkaloid is considered to be involved in the pathogenesis of alcoholism and to act as a false neurotransmitter. Recently the (S) enantiomer was proposed to be a precursor of morphine biosynthesis in the opium poppy. In this paper stereo-chemical characteristic of tetrahydropapaveroline in human brains was examined. In all four control human brains examined, only the (S)-tetrahydropapaveroline was detected. The concentrations were 0.12-0.22 pmol/g wet weight of brain tissue, and the presence of alcohol in blood did not affect the concentration. The results suggest that (S)-tetrahydropapaveroline may be enantio-selectively synthesized in human brain and it may be an intermediate of the de novo synthesis of morphine analogues.