2.5 Alkaloids Derived from Nicotinic Acid
The alkaloids derived from the nicotinic
acid are commonly known as the ‘Pyridine Alkaloids’. In general, the
alkaloids found in tobacco (Nicotiana tabacum, Solanaceae)
include a variety of alkaloids, such as: nicotine, anabasine, and
niacin (Vitamin B3, nicotinic acid). Interestingly, the ‘pyridine
unit’ has its origins in vitamin B3 (nicotinic acid); whereas,
a combination of a pyridine ring with a pyrrolidine ring gives rise to nicotine,
or a combination of a pyridine ring with a piperidine unit forms anabasine.
2.5.1 Pyridine Alkaloids
The three above
mentioned pyridine alkaloids, viz., nicotine, anabasine and
niacin, shall now be discussed individually in the sections that
follows:
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 pK2 10.96; 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.
Uses
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).
.
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.
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
3-Pyridinecarboxylic acid; (C6H5NO2).
Preparation It may be
prepared by the oxidation of nicotine** as given below.
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).
Uses
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.
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*
Sadykov and Timbekov, J. Appl. Chem., USSR,
29,
148 (1956).
**
MeElvain, S.M., Org. Synth. Coll.Vol
I, 385 (1941).
Source:Pharmacognosy And Pharmacobiotechnology By Ashutosh Kar
Source:Pharmacognosy And Pharmacobiotechnology By Ashutosh Kar
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