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At least 145 records · Page 8Linked to original sources
PubMed2005

Dichloro[(6R,7S,8S,14S)-(-)-sparteine-kappa2N,N']mercury(II).

In the title compound, [HgCl2(C15H26N2)], the chiral alkaloid (6R,7S,8S,14S)-(-)-L-sparteine acts as a bidentate ligand, with two Cl- ligands occupying the remaining coordination sites, producing a distorted tetrahedron. The N-Hg-N plane is twisted by 81.1 (2) degrees from the Cl-Hg-Cl plane. The mid-point of the N...N line does not lie exactly on the Cl-Hg-Cl plane but is tilted towards one of the N atoms by 0.346 angstroms. Similarly, the mid-point of the Cl...Cl line is tilted toward one of the Cl atoms by 0.163 angstroms. The packing structure shows that the complex is stabilized by two interatomic Cl...H contacts involving both Cl atoms and the methylene or methine H atoms of the (-)-sparteine ligand.

Journal Article↗
PubMed1989

[Stereospecific hydroxylation of (+)-sparteine (pachycarpine) in the rat].

Pachycarpine (4), the optical antipode of the lupine alkaloid (-)-sparteine (1), has been prepared from (-)-lupanine; its metabolism was studied in rats. After isolation and chromatographic purification, streochemically homogeneous (+)-(4S)-hydroxysparteine (7) was identified as the major urinary metabolite by use of mass spectrometry and high-field NMR-spectroscopy.

Animals↗
PubMed1995

Lack of relationship between quinidine pharmacokinetics and the sparteine oxidation polymorphism.

Quinidine is a very potent inhibitor of CYP2D6, but the role of the enzyme in the biotransformation of quinidine has only been investigated in a single in vitro study and in two small in vivo experiments, with contradictory results. The present investigation was designed to present definite evaluation of whether quinidine is metabolised by CYP2D6. Eight poor metabolizers (PM) and 8 extensive metabolizers (EM) of sparteine each took one oral dose of 200 mg quinidine. In the EM, the total clearance, the clearance via 3-hydroxylation and the clearance via N-oxidation, were 33, 3.7 and 0.23 l.h-1, respectively. In the PM, the corresponding values were 29, 3.1 and 0.18 l.h-1, respectively. There were no statistically significant differences between EM and PM in any of these pharmacokinetic parameters. It is concluded that CYP2D6 is not an important enzyme for the oxidation of quinidine.

Adult↗
PubMed1993

Inhibition by paroxetine of desipramine metabolism in extensive but not in poor metabolizers of sparteine.

Nine extensive metabolizers (EMs) and eight poor metabolizers (PMs) of sparteine took a single oral dose of 100 mg of desipramine HCI before and while taking paroxetine 20 mg per day. Before paroxetine, the median of the total desipramine clearance was 7 times higher in EMs than in PMs (102 and 15 l.h-1 respectively). This confirms that desipramine is extensively metabolized via the sparteine/debrisoquine oxidation polymorphism i.e. by CYP2D6. During paroxetine, the median clearances were 22 l.h-1 and 18 l.h-1 in EMs and PMs respectively. The 5-fold decrease in clearance in EMs when desipramine was co-administered with paroxetine confirms that paroxetine is a potent inhibitor of CYP2D6. The lack of effect on clearance in PMs shows that paroxetine is a selective inhibitor of CYP2D6, which is absent from the livers of PMs. Before paroxetine, the median of desipramine clearance via 2-hydroxylation was 40-times higher in EMs than in PMs (56 and 1.4 l.h-1 respectively), but during paroxetine, it was only 2-times higher (6 and 2.9 l.h-1 respectively). The increase in this clearance in PMs suggests that paroxetine is an inducer of the alternative, unidentified P450(s) which catalyze(s) the formation of 2-OH-desipramine in this phenotype. Before paroxetine, the median amounts of 2-OH-desipramine glucuronide recovered in urine were 69% and 68% of the total recovery of 2-OH-desipramine in urine in EMs and PMs respectively. During paroxetine, the corresponding values were 77% and 84%.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Oral↗
PubMed1986

Pharmacokinetics and metabolism of quinidine in extensive and poor metabolisers of sparteine.

The pharmacokinetics and metabolism of quinidine were investigated in extensive and poor metabolisers of sparteine. No differences in plasma clearance, terminal half life, volume of distribution or cumulative urinary excretion of quinidine, 3-hydroxyquinidine and quinidine-N-oxide were observed between phenotypes. Thus, it is unlikely that quinidine metabolism is controlled by the sparteine/debrisoquine gene locus.

Adult↗
PubMed1987

Severe complications of antianginal drug therapy in a patient identified as a poor metabolizer of metoprolol, propafenone, diltiazem, and sparteine.

A 47-year-old patient suffering from coronary artery disease was admitted to the CCU in shock with III. AV block, severe hypotension, and impairment of ventricular function. One week prior to admission a therapy with standard doses of metoprolol (100 mg t.i.d. and then 100 mg b.i.d.) had been initiated. Two days before admission diltiazem (60 mg b.i.d.) was prescribed in addition. Analyses of a blood sample revealed unusually high plasma concentrations of metoprolol (greater than 3000 ng/ml) and diltiazem (526 ng/ml). The patient recovered within 1 week following discontinuation of antianginal therapy. Three months later the patient was exposed to a single dose of metoprolol, diltiazem, propafenone (since he had received this drug in the past), and sparteine (as a probe for the debrisoquine/sparteine type polymorphism of oxidative drug metabolism). It was found that he was a poor metabolizer of all four drugs, indicating that their metabolism is under the same genetic control. Therefore, patients belonging to the poor-metabolizer phenotype of sparteine/debrisoquine polymorphism in drug metabolism, which constitutes 6.4% of the German population, may experience adverse drug reactions when treated with standard doses of one of these drugs alone. Moreover, the coadministration of these frequently used drugs is expected to be especially harmful in this subgroup of patients.

Angina Pectoris↗
PubMed1987

Methoxyphenamine O-demethylase and 5-hydroxylase: a GLC-ECD assay to study their activities and their inhibition by debrisoquine and sparteine.

A GLC-ECD method is described for the determination of the O-desmethyl, N-desmethyl and aromatic 5-hydroxy metabolites of methoxyphenamine in liver homogenates. The O-desmethyl and 5-hydroxy metabolites are deficient in poor metabolizers of debrisoquine and sparteine and the Dark Agouti rat model of this human phenotype. The present analytical method can be useful in determining methoxyphenamine O-demethylase and 5-hydroxylase activities as well as identifying those substrates which inhibit these and are worthy of further study.

Animals↗
PubMed1993

Rapid determination of sparteine and its metabolites in urine.

A method is presented for the isolation, separation and determination of sparteine and its metabolites in urine. The isolation is based on rapid extraction with dichloromethane and pentane in a glass separator. For the separation and determination, capillary gas chromatography with nitrogen-phosphorus detection was used. The recovery of the method ranged from 81.6% to 94.8%, and the limit of determination varied between 0.2 and 0.5 microgram ml-1. For quantification, 17-ethylsparteine was used as the internal standard.

Adult↗
PubMed1977

Analogues of sparteine. 5. Antiarrhythmic activity of selected N,N'-disubstituted bispidines.

A series of seven N,N'-disubstituted bispidines, structurally analogous to the inner (B and C) rings of sparteine (1) and encompassing a range of lipophilicity in which 1 was centered, has been compared to 1 in regard to antiarrhythmic potency and acute toxicity. Several of the bispidines were of comparable potency, and all but one were somewhat less toxic than 1. The ability of the mononitrate salts of 1 and bispidines 6 and 7 to bind calcium and magnesium cations in Me2SO-d6 solvent has been evaluated by proton magnetic resonance analysis. No binding could be demonstrated under these conditions, which suggested that pharmacologic effects of these compounds may be due to properties other than direct binding of these cations.

Animals↗
PubMed2001

Novel sparteine-mediated enantio-dichotomic formal synthesis of R-(-)- and S-(+)-curcuphenol.

High and opposite enantiodiscriminations were observed between tertiary amides and secondary amides in the sparteine-mediated lateral metalation-allylation of 2-ethyl-m-toluamide derivatives (2a, 2e). The results described above have been applied for the formal synthesis of both enantiomers of curcuphenol. The brief mechanistic studies suggested that stereoinformation was introduced after the deprotonation step.

Animals↗
PubMed2003

Scope of enantioselective palladium(II)-catalyzed aerobic alcohol oxidations with (-)-sparteine.

Evaluation of the substrate scope for Pd(II)/ (-)-sparteine catalyzed aerobic oxidative kinetic resolution of secondary alcohols is disclosed. An improved system is found with use of tert-butyl alcohol solvent in which benzylic and aliphatic alcohols as well as alcohols containing olefins are effectively oxidatively resolved. For substrates that successfully undergo oxidative kinetic resolution, k(rel) values are generally between 10 and 20. Successful scale-up of various substrates to 10-mmol scale is described. Extension to oxidative desymmetrization of 1,3-meso-diols is successful with enantiomeric excesses ranging from 78 to 85%.

Alcohols↗
PubMed2000

Highly enantioselective syntheses of anti homoaldol products by (-)-sparteine-mediated lithiation/transmetalation/substitution of N-Boc allylic amines.

[reaction: see text](-)-Sparteine-mediated lithiation/transmetalation/substitution of N-Boc allylic amines provides anti-configured homoaldol precursors in yields of 38-85% and enantiomeric ratios of 83:17-99:1. Subsequent O-protection and hydrolysis allows access to O-protected homoaldol adducts in good yields. The absolute configurations of the homoaldol products have been assigned by calculation of optical rotations and by X-ray crystallography of derivatives. A stereochemical course of reaction for the lithiation/transmetalation/substitution sequence is proposed.

Amines↗
PubMed2002

Lobocyclamide B from Lyngbya confervoides. Configuration and asymmetric synthesis of beta-hydroxy-alpha-amino acids by (-)-sparteine-mediated aldol addition.

[reaction: see text] Lobocyclamide B, a cyclododecapeptide containing five beta-hydroxy-alpha-amino acid residues, was isolated from Lyngbya confervoides. This is the first reported occurrence of gamma-hydroxythreonine in a natural peptide. Optically active beta-hydroxy-alpha-amino acids required for configurational analysis of the title compound were prepared using a novel (-)-sparteine-mediated asymmetric aldol addition of N-(diphenylmethylene)glycine tert-butyl ester to aldehydes. The method is general for aliphatic and aryl aldehydes and notable for operational simplicity.

Amino Acids↗
PubMed2002

First asymmetric total synthesis of (+)-sparteine.

[reaction: see text] The total synthesis of (+)-sparteine was accomplished from 2,5-norbornadione in 15 steps and 15.7% overall yield. The key steps were two ring-expansion reactions, one involving an intramolecular Schmidt reaction and one using a novel variant of the photo-Beckmann rearrangement.

Cardiovascular Agents↗
PubMed2004

Total synthesis of (-)-alpha-kainic acid by (-)-sparteine-mediated asymmetric deprotonation-cycloalkylation.

[reaction: see text] We report a new enantioselective synthesis of (-)-alpha-kainic acid from d-serine methyl ester hydrochloride, based on a (-)-sparteine-mediated asymmetric deprotonation of an intermediate carbamate that, by stereospecific anti S(N)'S(E)' intramolecular cycloalkylation, leads to the pyrrolidine ring precursor of (-)-alpha-kainic acid, in high yield and diastereoselectivity. The intermediate pyrrolidine was further transformed to (-)-alpha-kainic acid in three steps.

Alkylation↗
PubMed2005

Stereocontrolled total synthesis of (-)-kainic acid. Regio- and stereoselective lithiation of pyrrolidine ring with the (+)-sparteine surrogate.

[reaction: see text] A stereocontrolled total synthesis of (-)-kainic acid is described. cis-3,4-Disubstituted pyrrolidine ring was constructed by [3 + 2] cycloaddition of azomethine ylide with chiral butenolide. The crucial introduction of carboxyl group at the C-2 position was executed by regio- and stereoselective lithiation of the pyrrolidine ring in the presence of a (+)-sparteine surrogate followed by trapping with carbon dioxide.

Kainic Acid↗
PubMed2006

Discovery of a practical direct O2-coupled Wacker oxidation with Pd[(-)-sparteine]Cl2.

The discovery of a direct O2-coupled Wacker oxidation with use of balloon pressure of O2 and low catalyst loading is described. Use of (-)-sparteine as a ligand on Pd prevents olefin isomerization and leads to selective formation of methyl ketones from terminal olefins in good yields. Oxidation of enantiomerically enriched substrates is reported with no observed racemization.

Catalysis↗