Alkaloids: types, biosynthesis and functions

Alkaloids

1. Classification, Biosynthesis and Functions of Alkaloids Submitted From: Submitted To: Aleena Stanley Dr. Elsam Joseph 1 stMSc Botany Associate Professor St.Teresa’s College Ekm St.Teresa’s College Ekm 1

2. What is an alkaloid? The term Alkaloid (Alk=Alkali, Old=Like) was proposed by W.Meissnerin in 1819 for basic nitrogen containing compounds of plant origin. It may be defined as physiologically active basic compound of plant origin in with atleast one nitrogen atoms form part of a cyclic system. Alkaloids are cyclic organic compounds containing nitrogen in a negative state of oxidation with limited distribution among living organisms. 2

3. Forms of Alkaloids: Free Bases Salts with organic acids e.g. Oxalic, acetic acids Salts with inorganic acids e.g. HCl,H 2 SO 4 Salts with special acids e.g. Meconic acid in O pium Glycosidal form e.g. Solanine in Solanum 3

4. Distribution and Occurrence: Rare in lower plants. Dicots are more rich in Alkaloids than Monocots Families rich in Alkaloids: Apocynaceae, Rubiaceae, Solanaceae and Papaveraceae. Families free from Alkaloids: Rosaceae, Labiatae Alkaloids occur in all plants parts, but are usually localized in one organ. 4

5. Distribution in plants All Parts – Datura Barks- Cinchona Seeds- Nux Vomica Roots- Aconite Fruits- Black pepper Leaves- Tobacco Latex- Opium 5

6. Classification of Alkaloids Classification based on botanical origin of alkaloids are also used, e.g. Papaver, Cinchona, Rauvolfia, Strychonos Alkaloids etc.. CLASSIFICATION BASED ON THEIR CHEMICAL NATURE Alkaloid that contain a ring system, which is called indole are referred as Indole Alkaloids. 6

7. PHARMACOLOGICAL CLASSIFICATION Depending on the physiological response, the alkaloids are classified under various pharmacological categories like E.g. Narcotic analgesics: Morphine Vasodilation: Ephedrine, Ergonovine Local anesthetic: Cocaine Hallucinating: Psilocybin TAXONOMIC CLASSIFICATION This method classifies the vast number of alkaloids based on their distribution in various Plant families like Solanaceae or Papillionaceous alkaloids. Preferably, they are grouped as per the name of the genus in which they occur. E.g. Ephedra, Cinchona etc. 7

8. BIOSYNTHETIC CLASSIFICATION This method gives significance to the precursor from which the alkaloids are biosynthesized in the plant. E.g. Ornithine- Tropane, Pyrrolidine, Pyrrolizidine. Tyrosine- Benzyl isoquinoline. Tryptophane-Indole alkaloids, Quinoline 8

9. CLASSIFICATION OF ALKALOIDS BASED ON PRIMARY GROUPS TRUE ALKALOIDS : The Alkaloids containing true heterocyclic rings are called True Alkaloids and they are classified according to the ring system present in the molecule . PROTOALKALOIDS : The Alkaloids which do not contain heterocyclic ring are called Protoalkaloids. PSEUDOALKALOIDS : Those alkaloids which are not derived directly from amino acids are called Pseudo-alkaloids. 9

10. BIOSYNTHESIS OF ALKALOIDS Biosynthesis of Protoalkaloids A typical protoalkaloid Hordenine is synthesized from amino acid tyrosine or phenylalanine. The methyl groups present in Hordenine originate from methionine by the process of methylation in presence of enzyme tyramine methylpherase. 10

11. Biosynthesis of True Alkaloids The true alkaloids may be derivative of (i) Pyrrolidine, (ii) Pyrolizidine, (iii) Pyridine, (iv) Piperidine, (v) Quinolizidine, (vi) Isoquinone, (vii) Indole, (viii) Quinoline and (ix) Imidazole PYRROLIDINE DERIVATIVES: The pyrrolidine ring is a part of skeleton of tropane alkaloids like hyoscyamine. It is synthesized through amino acid ornithine via an intermediate pyrrolidine 5- carboxylic acid. 11

12. PYRROLIZIDINE DERIVATIVES: It is synthesized from two ornithine molecules. The alkaloid contains pyrrolizidine nucleus made up of two pyrrolidine nuclei. e.g. Retronecine alkaloid. PYRIDINE DERIVATIVES: Alkaloid nicotine in higher plants, anaerobic yeast and bacteria is synthesized from nicotinic acid which in turn is formed from L-aspartic acid and glycerol. But in animals and aerobic fungi the nicotine is synthesized from tryptophan. 12

13. INDOLE DERIVATIVES: The indole ring of reserpine and agroclavine alkaloids arises from amino acid tryptophan. The tryptophan first yields ajmaline. The remaining part of the molecule arises from a monoterpine vie mevalonic acid(MVA). This part is indicated by bold lines in the fig: 13

14. The ergot alkaloids also arise from tryptophan but here a hemiterpene residue probably dimethyallyl pyrophosphate is involved which are condensed forming 4- dimethylallyl tryptophan is converted into agroclavine. Agroclavine provides the basic skeleton for the synthesis of other ergot alkaloids. 14

15. QUINOLINE AND IMIDAZOLE DERIVATIVES Quinoline derivative alkaloids like Cinchonine and Quinine are synthesized from tryptophan via an indole alkaloid like corynantheine. The imidazole alkaloids like pilocarpine are probably synthesized from histidine. Nothing more is known about the biosynthesis of imidazole alkaloids. 15

16. Biosynthesis of Pseudoalkloids Pseudo alkaloids include terpenoid derivatives which are usually derived from triterpenes. Two types of sterol alkaloids are found in nature: ( i ) those which are C-27 compounds derived from cholesterol (ii) alkaloids containing C-21 pregnane skeleton .( Steroid derivatives with carbon present at position 1 through 21) Pseudo alkaloids are synthesized in leaves rather than in the roots. E.g C-21 alkaloids are holarrhimine and conarrhimine . (which exists as esters) Holarrhimine Conarrhimine 16

17. FUNCTIONS OF ALKALOIDS They may act as protective against insects and herbivores due to their bitterness and toxicity. They are, in certain cases, the final products of detoxification in metabolic reactions, therefore considered as waste products of metabolism . They may provide nitrogen to the plant organ in case of nitrogen deficiency( source of nitrogen) They, sometimes acts as growth regulators in certain metabolic systems. They are utilized as a source of energy incase of deficiency in carbon dioxide assimilation, especially those alkaloids containing a sugar moiety. 17

18. Some Alkaloids are extremely poisonous (e.g. Ergot) Ergot Alkaloids caused epidemic poisoning on the Middle Ages in Europe as a result of feeding on rye bread contaminated with the fungus The extracts of this plants containing such alkaloids have long been used as arrow poisons in hunting and warfare. E.g. Curare extract that contains tubocurarine alkaloid.(muscle relaxant) Belladonna has been mixed with food for the purpose of murdering. 18

19. Applications Of Alkaloids MEDICINE Medical use of alkaloid-containing plants has a long history, and thus when the first alkaloids were isolated in the 19 th cent. Many alkaloids are still used in medicines, usually in the form of salts . e.g. Ajamaline (Alkaloid) (anti-arrhythmic) Reserpine( anti-hypertensive) 19

20. Many synthetic and semisynthetic drugs are structural modifications of the alkaloids, which were designed to enhance or change the primary effect of the drug and reduce unwanted side-effects. E.g . Naloxone Human Foods and Drinks The plants in the human diet in which alkaloids are present are not only coffee seeds (caffeine), tea leaves (caffeine, theophylline) but also tomatoes (tomatine) and potatoes (solanine). The common alkaloid caffeine improves the taste and are mainly used by the sports men. 20

21. AGRICULTURE Prior to the development of a wide range of relatively low-toxic synthetic pesticides, some alkaloids, such as salts of nicotine and anabasine, were used as insecticides. USES OF PSYCHOACTIVE DRUGS Cocaine, caffeine and cathinone-Stimulants of CNS Mescaline and many Indole alkaloids (psilocybin, ibogaine)-Hallucinogen Morphine and Codeine – Narcotic pain killers. 21

22. Caffeine: Which occurs in coffee, tea and cocoa is a central nervous system stimulant. It is also used as antidote to barbiturate and morphine poisoning. Emetine: Key alkaloid used in the treatment of amebic dysentery and other protozoal infections. Ephedrine: It causes peripheral contraction of arterioles and it is used to correct low blood pressure conditions and also to dilate the pupil of the eye. As a bronchodilator it is used in allergic conditions like asthma. 22

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