Alkaloids Derived from Ornithine

2.6 Alkaloids Derived from Ornithine

A non-protein amino acid, L-ornithine, usually constitutes an integral part of the ‘urea-cycle’ in animals, wherein it is eventually produced from L-arginine in a reaction sequence catalyzed by the enzyme arginase as given below:

Evidently, L-ornithine possesses d-and a-amino moieties, and the N-atom from the former moiety which is eventually incorporated into the alkaloid structures along with the C-chain, except for the carboxyl function. Thus, the L-ornithine exclusively provides a C₄N building block to the alkaloid structure; not only as a pyrrolidine ring system, but also as a part of the tropane alkaloids. Nevertheless, the reactions of ornithine are fairly comparable to those of lysine, which in turn provides a C₅N unit bearing its ε-amino moiety.

The various alkaloids derived from ornithine may be categorized into three heads, namely:

(i) Pyrrolidine Alkaloids,

(ii) Tropane Alkaloids, and

(iii) Pyrrolizidine Alkaloids.

The above categories of alkaloids shall be discussed separately hereunder.

2.6.1 Pyrrolidine Alkaloids

The three glaring examples of pyrrolidine alkaloids are, namely: hygrine, cuscohygrine and stachydrine, which would be discussed below:

A. Hygrine

Biological Sources It occurs in the leaves of Erythroxylon coca Lam., (Erythroxylaceae) (Coca); and the roots of Withania somniferum (L.) Dunal. (Solanaceae) (Ashwagandha).

Chemical Structure

(R)-1-(1-Methyl-2-pyrrolidinyl)-2-propanone; (C₈H₁₅NO).

Characteristic Features

1. It is a liquid having bp11 76.5°C; bp₁₄ 81°C; n_D²⁰1.4555.

2. It is soluble in dilute mineral acids, chloroform and ethanol; and slightly soluble in water.

Identification Test It forms oxime readily (C₈H₁₆N₂O) which is obtained as crystals from ether having mp 123-124°C.

Uses The drug is broadly used as a sedative, hypnotic laxative and diuretic.

B. Cuscohygrine

Synonyms Cuskhygrine; Bellaradine.

Biological Sources It is obtained from the roots of Atropa belladona L. (Solanaceae) (Belladona, Deadly Nightshade); roots of Datura innoxia Mill. (Solanaceae) (Thorn Apple) upto 5-30%; seeds of Datura metal L. (Solanaceae) (Unmatal, Metel, Hindu Datura); leaves of Hyocyamus niger L. (Solanaceae) (Henbane, Henblain, Jusquaime); herb of Mandragora officinarum L. (Solanaceae) (Mandrake, Loveapple); rhizome of Scopolia carniolica Jacq. (Solanaceae) (Scopolia); and the roots of Withania somniferum (L.) Dunal (Solanaceae) (Ashwagandha).

Chemical Structure

1, 3-Bis (1-methyl-2-pyrrolidinyl)-2-propanone; (C₁₃H₂₄N₂O).

Isolation It is isolated from the naturally occurring plant sources by standard method.*

Characteristic Features

1. It is a oily liquid having bp₂₃ 169-170°C; bp₁₄ 152°C; bp₂ 118-125°C; d₄²⁰ 0.9733; n_D²⁰ 1.4832.

2. It is found to be miscible with water; and freely soluble in ethanol, ether, and benzene.

Identification Tests

1. Cuscohygrine Hemiheptahydrate: Its needles have mp 40°C.

2. Cuscohygrine Hydrobromide (C₁₃H₂₄N₂O.2HBr): It forms prisms from ethanol having mp 234°C.

C. Stachydrine

Synonyms Methyl hygrate betaine; Hygric acid methylbetaine.

Biological Sources It is obtained from the forage of Achillea millefolium L. (Asteraceae) (Yarrow); flowers of Chrysanthemum cinerarifolium (Trevir.) Vis. (Asteraceae) (Pyrethrum, Dalmatian Insect

Flower); branches of Lagochilus inebrians Bunge (Lamiaceae) (Intoxicating Mint); dry plant of, Leonurus cardiaca (L.) (Lamiaceae) (Motherwort); the ‘betaine fraction’ of alfalfa Medicago sativa L. (Fabiaceae) (Alfalfa) (0.785%); and herbage of Stachys officinalis (L.) Trevisan (Lamiaceae) (Betony).

Chemical Structure

(S)-2-Carboxy-1, 1-dimethylpyrrolidinium inner salt; (C₇H₁₃NO₂).

Isolation It has been isolated by reported method by Schulze** and Jahns.***

Characteristic Features

1. It is obtained as monohydrate deliquescent crystals having mp 235°C (anhydrous).

2. It is sweetish in taste.

3. It is soluble in water, dilute mineral acids and ethanol;

4. It isomerizes at the mp to methyl hygrate.

Identification Tests

1. Stachydrine Hydrochloride (C₇H₁₇NO₂.HCl): Its large prisms are obtained from absolute ethanol which gets decomposed at 235°C. It is very soluble in water and soluble in 13 parts of ethanol.

2. Stachydrine Acid Oxalate (C₇H₁₃NO₂.C₂H₂O₄): Its needles have mp 106°C. It is practically insoluble in absolute ethanol.

3. Stachydrine Aurichloride (C₇H₁₃NO₂.HAuCl₄): Its yellow needles have mp 225°C (rapid heating). It is quite soluble in hot water, but practically insoluble in cold water.

4. Stachydrine Platinichloride Tetrahydrate (C₇H₁₇NO₂)₂.H₂PtCl₆.4H₂O): It is obtained as orange crystals decomposing at 210-220°C (rapid heating). It is found to be very soluble in dilute ethanol and water. It may also be obtained with two moles of water of crystallization.

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* Liebermann, Ber., 22, 679 (1898)

** Sehulze, Ber. 26, 939 (1893);

*** Jahns, Ber. 29, 2065 (1896);

2.6.2 Tropane Alkaloids

Tropane is a bicyclic compound obtained by the condensation of one mole each of pyrrolidine and piperidine as shown below.

Tropane is regarded as the principle base of a plethora of alkaloids obtained from various members of the natural order, viz., Solanaceae, Erythroxylaceae, Convolvulaceae, and Dioscoreaceae. It essentially consists of a 7-carbon bicyclic ring with a N-atom strategically bridged between C-1 and C-5 and providing a C₇N unit. It is, however, pertinent to mention here that the tropane base contains two chiral centres (i.e., asymmetric C-atoms), namely: C-1 and C-5, but surprisingly it does not exhibit any optical activity (an exception) by virtue of the fact that intramolecular compensation prevails. It happens to be a meso-compound. A few important members belonging to the tropane alkaloids are, namely: atropine, cocaine, cinnamoyl cocaine, ecgonine and hyoscyamine. These alkaloids shall now be treated individually in the sections that follows:

A. Atropine

Synonyms Tropine tropate; dl-Hyoscyamine; dl-Tropyl Tropate; Tropic acid ester with Tropine.

Biological Sources It is obtained from the roots and leaves of Atropa belladona Linn. (Solanaceae) (Belladona); and the seeds and leaves of Datura stramonium Linn. (Syn.: Datura tatula Linn.) (Solanaceae) (Jimson Weed, Thorn Apple, Stramonium), besides other species of Solanaceae, such as: D. metel Linn.; D. innoxia Mill., D. alba Nees.; and D. fastuosa Linn.

Chemical Structure

1α H, 5α H-Tropan-3α-ol (±)-tropate (ester); (C₁₇H₂₃NO₃).

Characteristic Features

1. Atropine is obtained as long orthorhombic prisms from acetone having mp 114-116°C.

2. It usually sublimes in high vacuum at 93-110°C.

3. It has a dissociation constant pK 4.35; and the pH of a 0.0015 molar solution is 10.0.

4. Solubility: 1 g dissolves in 455 ml water; 90 ml water at 80°C; 2 ml ethanol; 1.2 ml ethanol at 60°C; 27 ml glycerol; 25 ml ether, 1 ml chloroform; and in benzene.

Identification Tests It forms various types of salts, namely:

1. Atropine Hydrochloride (C₁₇H₂₃NO₃.CH₃NO₃): The granular crystals have mp 165°C. It is soluble in water and ethanol. The pH of 0.05 molar solution is 5.8.

2. Atropine Methyl Bromide (C₁₇H₂₃NO₃.CH₃Br) (Tropin): Its crystals have mp 222-223°C. It is soluble in 1 part of water, slightly soluble in ethanol, and practically insoluble in ether and chloroform.

3. Atropine Methylnitrate (C₁₇H₂₃NO₃.CH₃NO₃) (Methylatropine nitrate, Eumydrin, Metropine, Harvatrate, Metanite, Ekomine): Its crystals have mp 163°C. It is found to be freely soluble in water or ethanol; and very slightly soluble in chloroform and ether.

4. Atropine Sulphate Monohydrate [(C₁₇H₂₃NO₃)₂.H₂SO₄.H₂O] (Atropisol): It is obtained as either crystals or powder with mp 190-194°C. It is inactive optically. It has a very bitter taste. It shows pH ~ 5.4. Its bitterness is threshold 1:10,000. It is found to be incompatible with a host of substances, such as, tannin, alkalies, salts of gold and mercury, borax, bromides, iodides, benzoates and vegetable decoctions or infusions.

Its solubility profile is: 1 g dissolves in 0.4 ml water; in 5 ml cold and 2.5 ml boiling ethanol; in 2.5 ml glycerol; 420 ml chloroform and 3000 ml ether.

Uses

1. It is used in preanaesthetic medication.

2. It is employed as an anticholinergic agent.

3. It is also used as a mydriatic.

4. It is employed as an antidote in opium and chloral hydrate poisoning.

5. It is frequently employed to minimize spasm in cases of intestinal gripping caused due to strong purgatives.

6. It also find its applications to reduce such secretions as: saliva, sweat, and gastric juice.

B. Cocaine

Synonyms 2β-Carbomethoxy-3β-benzoxytropane; l-Cocaine; β-Cocaine; Benzoylmethylecgonine; Ecgonine methyl ester benzoate.

Biological Sources It is obtained from the leaves of Erythroxylon coca Lam. and other species of Erythroxylon, (Erythroxylaceae); and leaves of Erythroxylon truxillense Rusby (Erythroxylaceae).

Chemical Structure

[IR-(exo, exo]-3-(Benzoyloxy)-8-methyl-8-azabicyclol [3, 2, 1] octane-2-carboxylic acid methyl ester; (C₁₇H₂₁NO₄).

Isolation Cocaine is extracted from the plant by digestion either with sodium carbonate solution or with lime water and by subsequent solvent extraction using petroleum ether (bp 160-180°C; or 200-220°C). The combined petroleum ether extract is shaken up with dilute HCl. The solution of hydrochloride thus obtained is concentrated carefully in a thin-film evaporator. In case, the leaves are rich in cocaine content, as in the Peruvian coca leaves, a major portion of cocaine gets separated as crystals.

Characteristic Features

1. Cocaine is obtained as the monoclinic tablets from ethanol having mp 98°C.

2. It usually becomes volatile above 90°C; however, the resulting sublimate is not crystalline in nature.

3. Its physical parameters are as follows; bp_0.1, 187-188°C; [α]_D¹⁸  -35⁰ (50% ethanol); [α]_D²⁰  -16⁰ (C = 4 in chloroform); pK_a (15°C) 8.61 and pK_b (15°C) 5.59.

4. Solubility Profile: 1 g of cocaine dissolves in 600 ml of water; 270 ml of water at 80°C; 6.5 ml of ethanol; 0.7 ml of chloroform; 3.5 ml of ether; 12 ml of turpentine; 12 ml of pure olive oil; and 30-50 ml of liquid petrolatum. It is also soluble in acetone, carbon disulphide and ethyl acetate.

Identification Tests

1. Cocaine Permanganate: The addition of a drop of saturated solution of KMnO₄ to a solution of cocaine prepared in a saturated solution of alum gives rise to a violet crystalline precipitate due to the formation of cocaine permanganate. It clearly shows characteristic violet aggregates of plates when examined under the microscope.

2. Cocaine Hydrochloride (C₁₇H₂₁NO₄.HCl) (Cocaine Muriate): It is obtained as granules, crystals, or powder. It has a slightly bitter taste and usually numbs lips and tongue. Its physical characteristics are: mp ~ 195°C; [α]_D – 72° (C = 2 in aqueous solution); 1 g dissolves in 0.4 ml of water; 3.2 ml cold and 2 ml hot alcohol; 12.5 ml chloroform. It is also soluble in glycerol and acetone; and insoluble in ether or oils.

3. Cocaine Nitrate Dihydrate (C₁₇H₂₂N₂O₇.2H₂O): Its crystals have mp 58-63°C. It is freely soluble in water or ethanol; and slightly soluble in ether.

4. Cocaine Sulphate (C₁₇H₂₁NO₄.H₂SO₄): It is obtained as white, crystalline or granular powder, which is soluble in ethanol and water.

Uses

1. It is used as a local anaesthetic as it causes numbness.

2. Its main action is a CNS-stimulant and, therefore, categorized as ‘narcotic drugs’. It is a highly habit-forming drug.

C. Cinnamoyl Cocaine

Synonyms Ecgonine Methyl Ester; Cinnamoylcocaine; Cinnamoyl-methylecgonine; Ecgonine Cinnamate Methyl Ester.

Biological Source It is obtained from the leaves of Erythroxylon coca Lann. (Erythroxylaceae), particularly from the Javanese leaves.

Chemical Structure

[1R-(exo, exo)]-8-Methyl-3-[(1-oxo-3-phenyl-2-propenyl)oxy]-8-azabicyclol [3, 2, 1] octane-2-carboxylic acid methyl ester; (C₁₉H₂₃NO₄).

Isolation Instead of the Peruvian leaves the Java leaves of E. coca are treated in the same manner and fashion as described under cocaine earlier (section ‘B’). It has been observed that the mixed hydrochlorides mostly comprise of cinnamoyl cocaine which gets separated as fine needles.

Characteristic Features

1. It is obtained as fine needles having mp 121°C.

2. Its specific optical rotation is [α]_D – 4.7° (chloroform).

3. It is freely soluble in ether, ethanol and chloroform; and almost insoluble in water.

Identification Tests

1. It reduces an acidic solution of KMnO₄ in cold i.e., at ambient temperature, which helps to detect the presence of this alkaloid in an admixture with cocaine.

2. It undergoes hydrolysis when warmed with HCl to yield l-ecgonine, cinnamic acid and methanol.

D. Ecgonine

Biological Source It is also obtained from the leaves of Erythroxylum coca Lam. (Erythroxylaceae) (Coca) as its l-form.

Chemical Structure

[1R-(exo, exo)]-3-Hydroxy-8-methyl-8-azabicyclol [3, 2, 1] octane-2-carboxylic acid; (C₉H₁₅NO₃). It is the principal part of the cocaine molecule.

Isolation Ecgonine may be obtained by the hydrolysis of cocaine as given below:

Cocaine -------Hydrolysis----à  Ecgonine + Benzoic acid + Methanol

Characteristic Features

1. The l-form ecgonine monohydrate is obtained as triboluminescent, monoclinic prisms from ethanol having mp 198°C (anhydrous substance gets decomposed at 205°C).

2. Its specific optical rotation [α ]_D¹⁵  -45⁰ (C = 5); dissociation constants are: pK_a 11.11, and pK_b 11.22.

3. Solubility Profile: 1 g dissolves in 5 ml water, 67 ml ethanol, 20 ml ethanol, 75 ml ethyl acetate; sparingly soluble in ether, acetone, benzene, chloroform and petroleum ether.

Identification Tests

1. Ecgonine Hydrochloride (C9H15NO3.HCl): It is obtained as the triclinic plates obtained from water having mp 246°C; [α]_D¹⁵  -59⁰ (C = 10); soluble in water and slightly in ethanol.

2. dl-Ecgonine Trihydrate: It is obtained as plates from 90% ethanol having mp 93-118°C (anhydrous substance gets decomposed at 212°C).

Uses It is mostly used as a topical anaesthetic.

E. Hyoscyamine

Synonyms l-Tropine Tropate; Daturine; Duboisine; l-Hyoscyamine; Cystospaz; Levsin; l-Tropic acid ester with Tropine; 3α-Tropanyl S-(–)-Tropate.

Biological Sources It is obtained from the roots and leaves of Atropa bella-dona L. (Solanaceae) (0.21%) (Thorn Apple); fruits, roots and leaves of Datura metel L. (Solanaceae) (Unmatal, Metel, Hindu Datura); leaves and seeds of Datura stramonium L. (Solanaceae) (Jimson Weed, Thorn Apple, Stramonium); root bark of Duboisia myoporoides R. Br. (Solanaceae) (Pituri, Corkwood Tree); young plants of Hyoscyamus niger L. (Solanaceae) (Henbane, Henblain Jusquaime); seeds of Lactuca virosa L. (Asteraceae) (Bitter Lettuce, Wild Lettuce); and the herb Mandragora officinarum L. (Solanaceae) (Mandrake, Loveapple).

Chemical Structure

1αH, 5αH-Tropan-3α-ol (–)-tropate (ester); (C₁₇H₂₃NO₃).

Isolation Hyoscyamine may be isolated from the Belladona leaves by adopting the following steps sequentially:

1. The finely powdered and sieved Belladona leaves is extracted with 95% (v/v) ethanol in a Soxhlet Apparatus till no more alkaloids come out from the marc. The ethanolic extract is concentrated to a syrupy residue under vaccuo and subsequently treated with dilute HCl. The resinous matter is separated by filtration and the resulting solution is further purified by shaking out with petroleum ether (40-60°C) several times.

2. The purified acidic solution thus obtained is made alkaline with ammonia solution (dilute) carefully and extracted with chloroform successively. The combined chloroform layer is once again shaken with dilute HCl, and the acidic solution made alkaline with dilute ammonia solution and extracted with chloroform successively.

3. The combined chloroform layer is removed by distillation under reduced pressure. The crude alkaloids thus obtained is neutralized with oxalic acid. The oxalates of atropine and hyoscyamine may be separated by fractional crystallization from acetone and ether wherein the hyoscyamine oxalate being more soluble gets separated as the second crop.

Characteristic Features

1. Hyoscyamine is obtained as silky tetragonal needles from evaporating ethanol having mp 108.5°C.

2. The physical parameters are: [α]_D²⁰ -21⁰ (ethanol); and dissociation constant K at 19° is 1.9 ×10–12.

3. Solubility Profile: 1 g dissolves in 281 ml water (pH 9.5), 69 ml ether, 150 ml benzene, and 1ml chloroform. It is freely soluble in dilute mineral acids and ethanol.

Identification Tests The various identification tests for hyoscyamine are, namely:

1. Gerrard Reaction: Hyoscyamine (and also atropine) responds to the Gerrard Reaction wherein about 5-10 mg of it reacts with mereuric chloride solution (2% w/v) in 50% ethanol to give rise to an instant red colouration without warming.

2. Schaer’s Reagent: A few mg of hyoscyamine when made to react with a few drops of the Schaer’s Reagent i.e., 1 volume of 30% H₂O₂ mixed with 10 volumes of concentrated sulphuric acid, produces a distinct green colouration.

3. Vitali-Morin Colour Reaction: A few mg of hyoscyamine (and also atropine) is treated with about 0.2 ml of fuming HNO₃, evaporated to dryness on the water-bath. To the residue is then added 0.5 ml of a 3% (w/v) solution of KOH in methanol, it gives a bright purple colouration, that changes to red and finally fades to colourless.

Note: (a) The 3% solution of KOH must be freshly prepared.

(b) The reaction is very sensitive i.e., upto 0.0001 mg of any of the alkaloids viz., strychnine, apomorphine, veratrine, physostigmine etc. give a positive test.

4. para-Dimethylaminobenzaldehyde Reagent: [Prepared by dissolving 2 g of

p-Dimethylaminobenzaldehyde in 6 g of H₂SO₄ to which 0.4 ml of water is added previously]. Add to 5-10 mg of hyoscyamine in an evaporating dish 2-3 drops of this reagent and heat on a boiling water-bath for several minutes. A distinct red colouration is produced that ultimately gets changed to permanent cherry red upon cooling.

5. Hyoscyamine Hydrobromide (C₁₇H₂₃NO₃.HBr): It is obtained as deliquescent crystals having mp 152°C; very soluble in water; 1 g dissolves in 3 ml ethanol; 1.2 ml chloroform and 2260 ml ether.

6. Hyoscyamine Hydrochloride (C1₇H₂₃NO₃.HCl): The crystals have mp 149-151°C; and freely soluble in water and ethanol.

7. Hyoscyamine Methyl Bromide (C₁₇H₂₃NO₃.CH₃Br) (N-Methylhyo-scyaminium bromide): The crystals have mp 210-212°C; and freely soluble in water, dilute ethanol; and slightly soluble in absolute ethanol.

8. Hyoscyamine Sulphate Dihydrate [(C₁₇H₂₃NO₃)₂.H₂SO₄.2H₂O] (Egacene, Peptard, Egazil Duretter): It is obtained as needles from ethanol having mp 206°C (when dry); [α]_D¹⁵ -29⁰ (C = 2); pH 5.3 (1 in 100); 1 g dissolves in 0.5 ml water and about 5.0 ml ethanol; and very slightly soluble in ether and chloroform.

Uses

1. It is mostly employed as an anticholinergic drug.

2. It exerts relaxation of bronchial and intestinal smooth museles (i.e., antispasmodic action).

3. It also inhibits contraction of the iris muscle of the eye to produce mydriasis.

4. It decreases significantly decreases the sweat gland and salivary gland secretions.

Biosynthesis of Hygrine, Cuscohygrine, Cocaine, Cinnamoyl Ecgonine (Methylecgonine) and Hyoscyamine The pyrrolidine ring system, present in hygrine and cuscohygrine, is formed initially as a ∆¹-pyrrolinium cation. The extra C-atoms required for hygrine formation are derived from acetate via acetyl-CoA; and the sequence appears to involve stepwise addition of two acetyl-CoA units as shown below:

These two steps may be explained as under:

(a) The enolate anion from acetyl-CoA serves as nucleophile for the pyrrolinium ion in a Mannichlike reaction, that may give rise to products having either R or S stereochemistry.

(b) An addition is caused by virtue of a Claisen condensation which essentially extends the sidechain, and the product is 2-substituted pyrrolidine, thereby retaining the thioester moiety of the second acetyl-CoA.

It has been observed that Hygrine and most of the naturally occurring tropane alkaloids is devoid of this specific C-atom, which is subsequently eliminated by suitable decarboxylation hydrolysis reactions. Interestingly, the genesis of the bicyclic structure of the tropane skeleton existing in either cocaine or hyoscyamine is accomplished due to the repeatation of the Mannich-like reaction stated above. These reactions are summarized in the description given under.

2.6.3 Pyrrolizidine Alkaloids

The bicyclic pyrrolizidine nucleus is formed by the utilization of two moles of ornithine and this pathway is accomplished via the intermediate putrescine. However, it has been observed that the plant sources usually synthesizing the pyrrolizidine alkaloids seem to be devoid of the decarboxylase enzyme that helps in the transformation of ornithine into putrescine; in fact, ornithine is really incorporated by way of arginine.

In nature, the pyrrolizidine alkaloids have a relatively broad stretch of distribution, but are specifically present in certain genera of the Leguminosae/Fabaceae (e.g., Crotalaria); the Compositae/Asteraceae (e.g., Senecio); and the Boraginaceae (e.g., Heliotropium, Symphytum, and Cynoglossum). Broadly speaking the pyrrolizidine bases do not occur in their free form, but are mostly found as esters with rare mono-or di-basic acids, the necic acids.

The two important alkaloids of this category are, namely: Retronecine and Senecionine, which shall be discussed as under:

A. Retronecine 

The most common base portion of the pyrrolizidine alkaloids is retronecine.

The ‘Necine’ bases are 1-methylpyrrolizidines of different stereochemical configurations and degree of hydroxylation which invariably occur as esters in alkaloids of Senecio, Crotalaria and a plethora of genera of the Boraginaceae as stated earlier.

Biological Source It is obtained from the herbs of Heliotropium europaeum L. (Boraginaceae) (Heliotrope, Turnsole).

Chemical Structure

(1R-trans)-2, 3, 5, 7, a-Tetrahydro-1-hydroxy-1 H-pyrrolizine-7-methanol; (C₈H₁₃NO₂).

Characteristic Features

1. It is obtained as crystals from acetone having mp 119-120°C.

2. It has the specific optical rotation [α]_D²⁰  +4.95⁰ (C = 0.58 in ethanol).

Identification Test It gives the racemic mixture i.e., (±) form as crystals from acetone having mp 130-131°C.

Uses

1. The plant is used for cancer and is popularly known as “Herbe Du Cancer” in Europe.

2. It is also used for snakebite and scorpion stings.

B. Senecionine

Synonym Aureine;

Biological Source The hepatotoxic alkaloid is obtained from the whole plant of Senecio vulgaris L. (Compositae); weed of Senecio aureus L. (Asteraceae) (Squaw Weed, Liferoot, Golden Groundsel); and preblooming plant of Tussilago farfara L. (Asteraceae) (Coltsfoot, Coughwort, Horse-Hoof).

Chemical Structure

12-Hydroxysenecionan-11, 16-dione; (C₁₈H₂₅NO₅): is described by Barger and Blackie (1936).*

Characteristic Features

1. It is obtained as plates having mp 236°C and a bitter taste.

2. Its specific optical rotation [α ]D25 -55.1⁰ (C = 0.034 in chloroform).

3. It is practically insoluble in water; freely soluble in chloroform; and slightly soluble in ether and ethanol.

Uses

1. It is used as an excellent drug to control pulmonary hemorrhage.

2. It is also used to hasten labour and check the pains of parturition.

Biosynthesis of Retronecine and Senecionine It has been observed that the plants synthesizing the above mentioned pyrrolizidine alkaloids seem to be devoid of the decarboxylase enzyme transforming ornithine into putrescine; in fact, ornithine is actually incorporated by way of arginine.

The various steps involved essentially in the biosynthesis of retronecine and senecionine are summarized as below:

1. Two moles of putrescine are condensed in an NAD+-dependent oxidative deamination reaction to yield the corresponding imine, which is subsequently transformed into homospermidine by the aid of NADH reduction.

2. The genesis of the creation of the pyrrolizidine skeleton is on account of the homospermidine molecule by a sequential series of interactions, such as: oxidative deamination, imine formation, intramolecular Mannich reaction, that specifically exploits the enolate anion produced from the aldehyde.

3. The ‘pyrrolizidine skeleton’ thus provides a C₄N unit from ornithine, together with an additional four C-atoms from the same amino acid precursor.

4. The senecionine is a diester of retronecine with senecic acid.

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* Barger, Blackie, J. Chem. Soc. 743 (1936)
Source:Pharmacognosy And Pharmacobiotechnology By Ashutosh Kar