Lactone Bitter Principles

2.2 Lactone Bitter Principles

The lactone bitter principles essentially possess a five-membered lactone ring which may be exemplified by the help of two glaring potent compounds belonging to this category, namely: α-santonin and picrotoxinin. These compounds shall now be discussed individually in the sections that follow:

2.2.1 α-Santonin

Synonym l-Santonin.

Biological Sources It is obtained from the dried unexpanded flower heads of Artemisia maritima L., sens. lat. (Compositae) (Levant Wormseed); and other spices of Artemisia found mostly in Russia, China and Turkestan besides the Southern Ural Region.

Chemical Structure

2.2 Lactone Bitter Principles

The lactone bitter principles essentially possess a five-membered lactone ring which may be exemplified by the help of two glaring potent compounds belonging to this category, namely:

α-santonin and picrotoxinin. These compounds shall now be discussed individually in the sections that follow:

2.2.1 α-Santonin

Synonym l-Santonin.

Biological Sources It is obtained from the dried unexpanded flower heads of Artemisia maritima L., sens. lat. (Compositae) (Levant Wormseed); and other spices of Artemisia found mostly in Russia, China and Turkestan besides the Southern Ural Region.

Chemical Structure

1, 2, 3, 4, 4α, 7-Hexahydro-1-hydroxy-α, 4α-8-trimethyl-7-oxo-2-naphthaleneacetic acid γ-lactone; (C₁₅H₁₈O₃).

Isolation The dried unexpanded flower heads of levant wormseed are treated with milk of lime so as to obtain calcium santoninate. The resulting product is subsequently converted into the corresponding soluble salt of sodium santoninate by the careful treatment with either sodium carbonate or sodium hydroxide. A stream of CO₂ is passed through the reaction mixture to get rid of calcium hydroxide as a precipitate of calcium carbonate which is filtered off conveniently. The filtrate is acidified with dilute sulphuric acid (6 N) when the crude santonin gets precipitated. The crude product thus obtained is made to dissolve in minimum quantity of ethanol (95%) and treated with activated charcoal powder to decolourize the solution. It is finally filtered off, ethanol is evaporated on an electric water bath and allowed to cool in a refrigerator overnight to obtain the pure α-santonin.

Characteristic Features The three different forms of santonin have the following characteristic features:

(a) (–)-Form of Santonin:

1. It may be obtained either as tabular crystals or as orthorhombic sphenoidal crystals having mp 170-173°C.

2. It is found to be practically tasteless with a positive bitter aftertaste.

3. Its specific optical rotation [α]_D²⁵ ranges between – 170° to 175° (C = 2 in ethanol).

4. It turns yellow on being exposed to light.

5. It causes irritation to the mucous membranes.

6. It has specific gravity d 1.187.

7. Solubility Profile: One part dissolves in 5000 parts of cold water, in 250 parts of boiling water, in 280 parts of 55% ethanol at 17°C, in 10 parts of boiling 50%-ethanol, in 44 parts of cold 90% ethanol, in 3 parts of boiling 90% ethanol, in 125 parts of cold ether, in 72 parts of boiling ether, and in 4.3 parts of cold chloroform. (b) (+)-Form of Santonin:

1. It is obtained as colourless plates from methanol having mp 172°C.

2. Its specific optical rotation [α]_D²⁰ + 165.9° (C = 1.92 in ethanol).

(c) (±)-Form of Santonin:

1. It is obtained as colourless plates from methanol having mp 181°C.

2. It has uv_max (ethanol): 241 nm (log ε 4.10).

Identification Tests The various identification tests for α-santonin are as stated below:

1. Chromosantonin (Photosantonin): Santonin is fairly stable in air, however, it turns yellow on exposure to light whereby it gets converted into its isomeric form chromosantonin, also known as photosantonin. The latter may be regenerated into santonin by simply crystallisation from ethanol.

2. Santonin when warmed with ethanolic solution of KOH or NaOH, it first and foremost produces a violet-red colouration, which gradually alters to reddish-yellow.

3. Heat 0.01 g of santonin with 2 ml of a mixture of sulphuric acid and water (1 : 1) no colour is produced apparently; but on the addition of 2-3 drops of dilute FeCl₃ solution (0.1% w/v) to the hot liquid a violet colouration is produced instantly.

4. Santonin when dissolved in a few drops of ethanol containing furfural, 2 ml of concentrated H₂SO₄ and the resulting mixture is heated in a porcelain dish over water-bath it gives a purplered colouration that gets changed to bluish-violet, to dull blue, and finally to almost black.

5. Santonin 0.1 g when dissolved in 5 ml of ethanol (95% v/v) gives a clear solution which being neutral to litmus paper and is levorotatory.

Uses

1. It is mostly used as an anthelmintic (Nematodes).

2. It is very efficient in its action on round worms; but shows less effect on the thread worms and none on taenia.

2.2.2 Picrotoxinin

Biological Sources It is the toxic component of picrotoxin obtained from the seed of Anamirta cocculus L. Wight & Arn. (Menispermaceae); and also found in Tinomiscium philippinense Diels.

Chemical Structure

[1aR – (1aα, 2aβ, 3β, 6β, 6aβ, 8aS*, – 8bβ, 9R*)]-Hexahydro-2a-hydroxy-8b-methyl-9-(1-methylethenyl)-3, 6-methano-8H-1, 5, 7-trioxacyclopenta [ij] cycloprop [a] azulene-4, 8 (3H)-dione; (C₁₅H₁₆O₆).

Preparation Picrotoxinin may be prepared from picrotoxin by the method suggested by Horrmann.*

Characteristic Features

1. It is obtained in two different forms: first—as large prisms, and secondly—as small crystals containing water having mp 209.5°C.

2. Its specific optical rotations are: [α]¹⁷_D + 4.4° (C = 4.28 in absolute alcohol); and + 3.49° (C =7.57 in acetone).

3. It is found to be soluble in hot common organic solvents; and also in cold chloroform and ethanol.

4. Nevertheless it has a very bitter taste.

Uses

1. It is employed as a CNS and respiratory stimulant.

2. It may also be used as an antidote to barbiturates.

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* Horrmann, Ber., 45, 2090 (1912).

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Source:Pharmacognosy And Pharmacobiotechnology By Ashutosh Kar