Pyridine Alkaloids

2.5.1 Pyridine Alkaloids

The three above mentioned pyridine alkaloidsviz., nicotine, anabasine and niacin, shall now be discussed individually in the sections that follows:

Biosynthesis of Castanospermine and Swainsonine

A. Nicotine

Synonyms Nicolan; Nicabate; Nicoderm; Nicotell TTS; Nicopatch; Nicotinell; Habitrol; Tabazur.
Biological Sources It is obtained from the dried leaves of Nicotiana tabacum Linn., (Solanaceae)
(Virginia Tobacco; Tobacco); sprouts of Asclepias syriaca L. (Asclepiadaceae) (Common Milkweed); dried leaves and roots of Datura metel L. (Solanaceae) (Unmatal, Metel, Hindu
Datura); leaves of Duboisia myoporoides R. Br. (Solanaceae) (Corkwood Tree, Pituri); fresh forage of Equisetum arvense L. (Equisetaceae) (Field Horsetail); herbs of Equisetum hyemale L. (Equisetaceae) (Shavegrass, Great Scouring Rush); leaves of Erythroxylum coca Lam., (Erythroxylaceae) (Coca); fruits and leaves of Nicotiana glauca R. Grah. (Solanaceae) (Tree Tobacco); and leaves of Nicotiana rustica Linn. (Solanaceae)–present upto 2-8%.
Chemical Structure

(S)-3-(1-Methyl-2-pyrrolidixyl) pyridine; (C10H14N2).
Preparation Commercial nicotine is entirely a byproduct of the tobacco industry; and the extraction from-N. tabacum has been described in literature.*
Characteristic Features
1. It is a colourless to pale yellow oily liquid, very hygroscopic in nature, and turns brown on exposure to air and light.
2. It has an inherent acrid burning taste.
3. It develops the odour of pyridine.
4. It has a bp745 247°C with partial decomposition; and bp17 123-125°C.
5. It is a steam-volatile product.
6. Its physical parameters are; nD201.5282 ; d420 1.0097 ;[α] D20 - 1690; pK1 (15°) 6.16 and pK10.96; and pH of 0.05 M solution 10.2.
7. It readily forms salts with almost any acid; and double salts with many metals and acids.
8. Solubility: It is miscible with water below 60°C; and on mixing nicotine with water the volume contracts. However, it is found to be very soluble in chloroform, ethanol, ether, petroleum ether and kerosene oils.
Identification Tests
1. Nicotine Hydrochloride (C10H14N2.HCl): It is obtained as deliquescent crystals having specific rotation [α] D20  +1040 (p = 10).
2. Nicotine Dihydrochloride (C10H14N2.2HCl): The deliquescent crystals are extremely soluble in water and ethanol.
3. Nicotine Sulphate [(C10H14N2)2.H2SO4] (Synonym: Nicotine neutral sulphate): It is obtained as hexagonal tablets having optical rotation [α] D20  +880 (p = 70); and is soluble in water and ethanol.
4. Nicotine Bitartrate (C10H14N2.2C4H6O6) (Synonym: Nicotine Tartrate): It is obtained as the dihydrate, crystals having mp 90 °C; [α] D20  +260 (C = 10); and is found to be very soluble in ethanol and water.
5. Nicotine Zinc Chloride Double Salt Monohydrate (C10H16Cl4N2Zn-H2O): It is very soluble in water; and sparingly soluble in ether and ethanol.
6. Nicotine Salicylate (C17H20N2O3): (Synonym: Eudermol): It is obtained as hexagonal plates having mp 118°C; [α] D20  +130 (C = 9); and is found to be freely soluble in ethanol and water.
1. It is used extensively as an insecticide and fumigant.
2. It finds its application as a contact poison’ in the form of soap i.e., as its oleate, laurate and naphthenate salts.
3. It is also used as a ‘stomach poison’ in combination with bentonite.
4. One of its recent applications nicotine is employed as chewable tablets of lozenges for the treatment of smoking withdrawl syndrome.
5. It possesses a unique action on the autonomic ganglia which it first stimulates and subsequently depresses ultimately leading to paralysis.
* Gattermann, Wieland, ‘Laboratory Methods of Organic Chemistry’ New York, 24th edn., (1937)

B. Anabasine

Synonym Neonicotine;
Biological Sources It is obtained from the leaves of Duboisia myoporoides R. Br. (Solanaceae)
(Corkwood tree; Pituri); fruits and leaves of Nicotiana glauca R. Grah. (Solanaceae) (Tree Tobaccoclaimed to be the richest source of anabasine (1.2%); leaves of Nicotiana tabacum L. (Solanaceae) (Tobacco, Tabac, Virginia Tobacco); and also the leaves of Anabasis aphylla L. (Chenopodiaceae).
Chemical Structure 3-(2-Piperidixyl) pyridine; (C10H14N2).
Anabasine Synonym Neonicotine
Isolation Anabasine is extracted on a large scale in Russia; and the industrial extraction processes have been reported by Sadykov and Timbekov* (1956).
Characteristic Features
1. It is a liquid freezing at 9°C; and boiling at 270-272°C; bp14 145-147°C; bp2 105°C.
2. Its physical parameters are: d420 1.0455; nD20 1.5430; and [α]D20 -8310
3. It is soluble in most organic solvents and water.
Identification Tests
1. Being a secondary amine it can form a nitroso derivative.
2. Anabasine Hydrochloride: Its specific optical rotation is [α]D  +16.50 (C = 10 in water).
Uses It is invariably employed as an effective insecticide.

C. Niacin

Synonyms Nicotinic Acid; Pellagra Preventive Factor (or P.P. Factor); Vitamin B3; Akotin; Daskil; Nicacid; Niacor; Nicangin; Nicobid; Nicolar; Niconacid; Nico-Span; Wampocap. The term ‘niacin’ has also been applied to nicotinamide.
Biological Sources It is widely distributed in nature; and appreciable quantities are found in fish, yeast, liver, and cereal grains.
Chemical Structure

Niacin Synonyms Nicotinic Acid; Pellagra Preventive Factor
3-Pyridinecarboxylic acid; (C6H5NO2).
Preparation It may be prepared by the oxidation of nicotine** as given below.

 N-Oxide Derivative (Oxiniacic Acid)
2. It sublimes without any decomposition.
3. It is a nonhygroscopic substance and fairly stable in air.
4. It shows uvmax : 263 nm; and pH 2-7 of a saturated solution.
5. Solubility: 1 g dissolves in 60 ml water; freely soluble in boiling water and ethanol; soluble in
propylene glycol; and insoluble in ether.
Identification Test
1. Niacin Sodium Salt Sesquihydrate (C6H4NNaO2.1½H2O) (Synonym: Direktan): It is obtained
as either white crystals or crystalline powder, which is stable in air. Its solubility profile are as
follows: 1 g dissolves in ~ 1.4 ml of water, in 60 ml ethanol, in 10 ml glycerol; and insoluble in
ether. The pH of aqueous solution is ~ 7.
2. N-Oxide Derivative (Oxiniacic Acid): It is obtained as needles mp 254-255°C (dec.) and uvmax
(0.1 N.H2SO4):220, 260 nm (€ 22400, 10200).

N-Oxide Derivative (Oxiniacic Acid)
1. It is used as antihyperlipoproteinemic agent.
2. It is a vital vitamin (enzyme cofactor).
Biosynthesis of Nicotine, Anabasine and Niacin Interestingly, plants such as Nicotiana make use of an altogether different pathway employing glyceraldehyde 3-phosphate and L-aspartic acid precursors as given under. Thus, the dibasic acid quinonilic acid features in the aforesaid pathway which upon decarboxylation gives rise to nicotinic acid.
It is pertinent to mention here that the formation of nicotine caused by a pyrrolidine ring derived from ornithine, quite possibly as the N-methyl-∆1-pyrrolinium cation gets hooked on to the pyridine ring present in nicotinic acid thereby displacing the carboxyl function during the course of reactions as depicted in (B). Further, a dihydronicotinic acid intermediate is most likely to be engaged permitting decarboxylation to the enamine 1,2-dihydropyridine. It, therefore, allows an aldol-type interaction with the N-methylpyrrolinium cation, and ultimately undergoes dehydrogenation of the dihydropyridine ring reversed to a pyridine ring yields nicotine. In this fashion, nornicotine is derived by the oxidative demethylation of nicotine.
Finally, anabasine is generated from nicotinic acid and lysine via the ∆1-piperidinium cation in an effectively analogous sequence as shown in (C) below.

Biosynthesis of Nicotine, Anabasine and Niacin
Biosynthesis of Nicotine, Anabasine and Niacin
* Sadykov and Timbekov, J. Appl. Chem., USSR, 29, 148 (1956).
** MeElvain, S.M., Org. Synth. Coll.Vol I, 385 (1941).

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