Sparteine is a class 1a

antiarrhythmic agent Antiarrhythmic agents, also known as cardiac dysrhythmia medications, are a class of drugs that are used to suppress abnormally fast rhythms (tachycardias), such as atrial fibrillation, supraventricular tachycardia and ventricular tachycardia. M ...

and sodium channel blocker. It is an

alkaloid Alkaloids are a broad class of natural product, naturally occurring organic compounds that contain at least one nitrogen atom. Some synthetic compounds of similar structure may also be termed alkaloids. Alkaloids are produced by a large varie ...

and can be extracted from scotch broom. It is the predominant alkaloid in '' Lupinus mutabilis'', and is thought to chelate the bivalent metals

calcium Calcium is a chemical element; it has symbol Ca and atomic number 20. As an alkaline earth metal, calcium is a reactive metal that forms a dark oxide-nitride layer when exposed to air. Its physical and chemical properties are most similar to it ...

and

magnesium Magnesium is a chemical element; it has Symbol (chemistry), symbol Mg and atomic number 12. It is a shiny gray metal having a low density, low melting point and high chemical reactivity. Like the other alkaline earth metals (group 2 ...

. It is not FDA approved for human use as an antiarrhythmic agent, and it is not included in the Vaughan Williams classification of antiarrhythmic drugs. It is also used as a

chiral Chirality () is a property of asymmetry important in several branches of science. The word ''chirality'' is derived from the Greek language, Greek (''kheir''), "hand", a familiar chiral object. An object or a system is ''chiral'' if it is dist ...

ligand In coordination chemistry, a ligand is an ion or molecule with a functional group that binds to a central metal atom to form a coordination complex. The bonding with the metal generally involves formal donation of one or more of the ligand's el ...

organic chemistry Organic chemistry is a subdiscipline within chemistry involving the science, scientific study of the structure, properties, and reactions of organic compounds and organic matter, organic materials, i.e., matter in its various forms that contain ...

, especially in syntheses involving organolithium reagents.

Biosynthesis

Sparteine is a lupin

containing a tetracyclic bis-quinolizidine ring system derived from three C₅ chains of

lysine Lysine (symbol Lys or K) is an α-amino acid that is a precursor to many proteins. Lysine contains an α-amino group (which is in the protonated form when the lysine is dissolved in water at physiological pH), an α-carboxylic acid group ( ...

, or more specifically, -lysine. The first intermediate in the biosynthesis is

cadaverine Cadaverine is an organic compound with the formula (CH2)5(NH2)2. Classified as a diamine, it is a colorless liquid with an unpleasant odor. It is present in small quantities in living organisms but is often associated with the putrefaction of Tiss ...

, the decarboxylation product of lysine catalyzed by the enzyme lysine decarboxylase (LDC). Three units of cadaverine are used to form the quinolizidine skeleton. The mechanism of formation has been studied enzymatically, as well as with tracer experiments, but the exact route of synthesis still remains unclear. Tracer studies using ¹³C-¹⁵N-doubly labeled cadaverine have shown three units of cadaverine are incorporated into sparteine and two of the C-N bonds from two of the cadaverine units remain intact. The observations have also been confirmed using ²H NMR labeling experiments. Enzymatic evidence then showed that the three molecules of cadaverine are transformed to the quinolizidine ring via enzyme bound intermediates, without the generation of any free intermediates. Originally, it was thought that conversion of cadaverine to the corresponding aldehyde, 5-aminopentanal, was catalyzed by the enzyme diamine oxidase. The aldehyde then spontaneously converts to the corresponding Schiff base, Δ¹-piperideine. Coupling of two molecules occurs between the two tautomers of Δ¹-piperideine in an aldol-type reaction. The imine is then hydrolyzed to the corresponding aldehyde/amine. The primary amine is then oxidized to an aldehyde followed by formation of the imine to yield the quinolizidine ring.

Via 17-oxosparteine synthase

More recent enzymatic evidence has indicated the presence of 17-oxosparteine synthase (OS), a transaminase enzyme. The deaminated cadaverine is not released from the enzyme, thus is can be assumed that the enzyme catalyzes the formation of the quinolizidine skeleton in a channeled fashion . 7-oxosparteine requires four units of pyruvate as the NH₂ acceptors and produces four molecules of alanine. Both lysine decarboxylase and the quinolizidine skeleton-forming enzyme are localized in chloroplasts.

References

External links

* {{Antiarrhythmic agents Antiarrhythmic agents Quinolizidine alkaloids Sodium channel blockers

Biosynthesis

Via 17-oxosparteine synthase

See also

References

External links