Pyrrolidine Alkaloids

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);