Sparteine
Encyclopedia
Sparteine is a class 1a antiarrhythmic agent
; a sodium channel blocker. It is an alkaloid
and can be extracted from scotch broom. It is the predominant alkaloid in Lupinus mutabilis
, and is thought to chelate the bivalents calcium
and magnesium
. It is not FDA approved for human use as an antiarrhythmic agent, and it is not included in the Vaughn Williams classification of antiarrhythmic drugs.
It is also used as a chiral
base
in organic chemistry
, and as a ligand
in organic chemical synthesis
.
containing a tetracyclic bis-quinolizidine ring system derived from three C5 chains of lysine
, or more specifically, L-lysine. The first intermediate in the biosynthesis is cadaverine
, 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. The breakdown of this mechanism is shown in figure 1; however, the intermediates, as mentioned before, were not isolated.
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 (Figure 2)., , 7-oxosparteine requires four units of pyruvate as the NH2 acceptors and produces four molecules of alanine (Figure 3). Both lysine decarboxylase and the quinolizidine skeleton-forming enzyme are localized in chloroplasts.
Antiarrhythmic agent
Antiarrhythmic agents are a group of pharmaceuticals that are used to suppress abnormal rhythms of the heart , such as atrial fibrillation, atrial flutter, ventricular tachycardia, and ventricular fibrillation....
; a sodium channel blocker. It is an alkaloid
Alkaloid
Alkaloids are a group of naturally occurring chemical compounds that contain mostly basic nitrogen atoms. This group also includes some related compounds with neutral and even weakly acidic properties. Also some synthetic compounds of similar structure are attributed to alkaloids...
and can be extracted from scotch broom. It is the predominant alkaloid in Lupinus mutabilis
Lupinus mutabilis
Lupinus mutabilis is a species of lupin grown in the Andes for its edible bean. Vernacular names include tarwi, tarhui, chocho, altramuz, Andean lupin, South American lupin, or pearl lupin....
, and is thought to chelate the bivalents calcium
Calcium
Calcium is the chemical element with the symbol Ca and atomic number 20. It has an atomic mass of 40.078 amu. Calcium is a soft gray alkaline earth metal, and is the fifth-most-abundant element by mass in the Earth's crust...
and magnesium
Magnesium
Magnesium is a chemical element with the symbol Mg, atomic number 12, and common oxidation number +2. It is an alkaline earth metal and the eighth most abundant element in the Earth's crust and ninth in the known universe as a whole...
. It is not FDA approved for human use as an antiarrhythmic agent, and it is not included in the Vaughn Williams classification of antiarrhythmic drugs.
It is also used as a chiral
Chirality (chemistry)
A chiral molecule is a type of molecule that lacks an internal plane of symmetry and thus has a non-superimposable mirror image. The feature that is most often the cause of chirality in molecules is the presence of an asymmetric carbon atom....
base
Base (chemistry)
For the term in genetics, see base A base in chemistry is a substance that can accept hydrogen ions or more generally, donate electron pairs. A soluble base is referred to as an alkali if it contains and releases hydroxide ions quantitatively...
in organic chemistry
Organic chemistry
Organic chemistry is a subdiscipline within chemistry involving the scientific study of the structure, properties, composition, reactions, and preparation of carbon-based compounds, hydrocarbons, and their derivatives...
, and as a ligand
Ligand
In coordination chemistry, a ligand is an ion or molecule that binds to a central metal atom to form a coordination complex. The bonding between metal and ligand generally involves formal donation of one or more of the ligand's electron pairs. The nature of metal-ligand bonding can range from...
in organic chemical synthesis
Chemical synthesis
In chemistry, chemical synthesis is purposeful execution of chemical reactions to get a product, or several products. This happens by physical and chemical manipulations usually involving one or more reactions...
.
Biosynthesis
Sparteine is a lupin alkaloidAlkaloid
Alkaloids are a group of naturally occurring chemical compounds that contain mostly basic nitrogen atoms. This group also includes some related compounds with neutral and even weakly acidic properties. Also some synthetic compounds of similar structure are attributed to alkaloids...
containing a tetracyclic bis-quinolizidine ring system derived from three C5 chains of lysine
Lysine
Lysine is an α-amino acid with the chemical formula HO2CCH4NH2. It is an essential amino acid, which means that the human body cannot synthesize it. Its codons are AAA and AAG....
, or more specifically, L-lysine. The first intermediate in the biosynthesis is cadaverine
Cadaverine
Cadaverine is a foul-smelling compound produced by protein hydrolysis during putrefaction of animal tissue. Cadaverine is a toxic diamine with the formula NH25NH2, which is similar to putrescine...
, 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. The breakdown of this mechanism is shown in figure 1; however, the intermediates, as mentioned before, were not isolated.
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 (Figure 2)., , 7-oxosparteine requires four units of pyruvate as the NH2 acceptors and produces four molecules of alanine (Figure 3). Both lysine decarboxylase and the quinolizidine skeleton-forming enzyme are localized in chloroplasts.