Introduction to Alkaloids

MASARYKOVA UNIVERZITA Pedagogická fakulta Katedra fyziky, chemie a odborného vzdělávání

Bakalářská práce

Brno 2017

Vedoucí práce: Autor práce: Mgr. Jiří Šibor, Ph.D. Aleš Bárta

Prohlášení:

„Prohlašuji, že jsem bakalářskou práci vypracoval samostatně, s využitím pouze citovaných pramenů, dalších informací a zdrojů v souladu s Disciplinárním řádem pro studenty Pedagogické fakulty Masarykovy univerzity a se zákonem č. 121/2000 Sb., o právu autorském, o právech souvisejících s právem autorským a o změně některých zákonů (autorský zákon), ve znění pozdějších předpisů.“

V Brně dne: 28.3.2017 …………………..

Aleš Bárta

Acknowledgement: I would like to thank to Mgr. Jiří Šibor, Ph.D. not only for the help he provided me with but also for his endless patience during our sessions which helped me complete this bachelor thesis.

Obsah INTRODUCTION AND GOALS ...... 6 WORKING APPROACH ...... 7 1 ALKALOIDS – CHARACTERISTICS ...... 8 1.1 HISTORY OF ALKALOID CHEMISTRY ...... 11 1.2 SIGNIFICANCE OF ALKALOID FORMATION FOR THE PRODUCER ORGANISM ...... 11 1.3 APPLICATIONS ...... 11 2 PHENYLETHYLAMINE DERIVATIVES ...... 13 2.1 MESCALINE ...... 13 2.2 EPHEDRINE AND NORPSEUDOEPHEDRINE ...... 14 3 PYRIDINE AND PIPERIDINE DERIVATIVES ...... 16 3.1 NICOTINE ...... 16 3.1.1 NICOTINE ISOLATION ...... 17 3.2 CONIINE ...... 18 4 PYRROLIDINE DERIVATIVES ...... 20 4.1 HYGRINE ...... 20 4.2 CUSCOHYGRINE ...... 21 5 TROPANE DERIVATIVES ...... 22 5.1 ATROPINE GROUP ...... 23 5.1.1 ATROPINE ...... 23 5.1.2 HYOSCYAMINE ...... 24 5.1.3 SCOPOLAMINE ...... 25 5.2 PSEUDOTROPINE GROUP ...... 25 5.2.1 ECGONINE ...... 26 5.2.2 PSEUDOECGONINE ...... 26 5.2.3 COCAINE ...... 27 6 INDOLE DERIVATVES ...... 29 6.1 SIMPLE-STRUCTURED COMPOUNDS ...... 29 6.1.1 GRAMINE ...... 29 6.1.2 BUFOTENINE ...... 30 6.1.3 PSILOCYBINE ...... 31 6.2 COMPLEX-STRUCTURED COMPOUNDS ...... 33 6.2.1 YOHIMBINE ...... 33 6.2.2 PHYSOSTIGMINE ...... 33 6.2.3 RESERPINE ...... 34 6.2.4 STRYCHNINE ...... 35 6.3 LYSERGIC ACID ...... 36 7 QUINOLINE DERIVATIVES...... 38 7.1 QUININE ...... 38 7.2 QUNIDINE ...... 39 8 ISOQUINOLINE DERIVATIVES ...... 40 8.1.1 PAPAVERINE ...... 41 8.1.2 LAUDANOSINE ...... 41 8.1.3 HYDRASTINE ...... 42 8.1.4 RETICULINE ...... 43 4

8.2 MORPHINE GROUP ...... 43 8.2.1 MORPHINE ...... 44 8.2.2 CODEINE...... 45 8.2.3 THEBAINE ...... 46 8.3 OTHER ISOQUINOLINE DERIVATIVES...... 46 8.3.1 BERBERINE ...... 46 8.3.2 TUBOCURARINE ...... 47 9 PYRROLIZIDINE DERIVATIVES ...... 48 9.1 MONOCROTALINE ...... 49 10 QUINOLIZIDINE DERIVATIVES ...... 50 10.1 LUPININE ...... 50 10.2 EMETINE ...... 51 10.3 (-)-SPARTEINE ...... 52 11 IMIDAZOLE DERIVATIVES ...... 53 11.1 PILOCARPINE ...... 53 11.2 MUSCARINE ...... 54 12 PURINE DERIVATIVES ...... 55 12.1 XANTHINE ...... 55 12.2 THEOPHYLLINE ...... 56 12.3 THEOBROMINE ...... 56 12.4 CAFFEINE ...... 58 12.5 CAFFEINE MICROSUBLUMATION ...... 60 13 STEROIDAL ALKALOIDS ...... 61 13.1 SOLANIDINE ...... 61 13.2 RUBIJERVINE ...... 61 13.3 TOMATIDINE ...... 61 13.4 PROOF OF SOLANINE PRESENCE IN POTATOES ...... 62 14 DITERPENE ALKALOIDS ...... 63 14.1 ACONITINE ...... 63 15 TROPOLONE DERIVATIVES ...... 65 15.1 COLCHICINE ...... 65 CONCLUSION ...... 66 SOURCES USED ...... 67 PICTURES AND THEIR SOURCES ...... 69 BIBLIOGRAPHIC NOTE ...... 76 ANNOTATION ...... 76 ANOTACE ...... 76 KEYWORDS ...... 77 KLÍČOVÁ SLOVA ...... 77

Introduction and Goals Alkaloids are an exceptional group of substances that have been known for thousands of years. Their toxicity has already been known in ancient times and later on caused the great interest of chemists and biochemists in studying those fascinating substances.

Alkaloids are chemicals we meet in everyday life and most of them have certain effect on our body functions. Some of them are well-known for their pharmacological effect. While some of them are important medicaments others are world-widely abused harmful, addictive and dangerous drugs.

The aim of this thesis is to create a unique textbook of Alkaloids. The thesis should work as a textbook for students of chemistry. Although, the thesis is written in English language the textbook should be suitable not only for native but also for non-native speakers of English. It should basically be an attempt to improve students´ knowledge of English in professional areas.

The textbook gives a basic description of what the Alkaloids are and their further division into several groups according to their chemical structure. The most important substances are then described in detail. The description contains substances´ characteristics, their occurrence in nature, their possible use or other interesting information that may initiate subsequent interest of the reader.

Working approach In the first part of this bachelor thesis the author created basic characteristics of the alkaloid compounds. Specifically, their chemical characterisation, their occurrence in nature and brief insight into alkaloid history. The second part of the thesis is comprised with the prominent groups of alkaloids and introduces the most important members of these groups. The author provides chemical definitions, IUPAC names, chemical formulas and application of the chosen alkaloid compounds.

To create this textbook of alkaloids the author used various materials. The structure of the thesis is based on [1] Bioorganická chemie by Karel Waisser and Karel Palát, Jr. Other important sources were [2] The Plant Alkaloids by Thomas Anderson Henry and [3] Biochemistry of Alkaloids by Mothes, Schütte and Luckner. The author also used other literary and internet sources for the creation of the thesis. To make up the alkaloid compound formulas the author was using Chemsketch program. The pictures included to the thesis are downloaded from the internet sources which allow they use, sharing and even use for commercial purposes.

1 ALKALOIDS – CHARACTERISTICS Alkaloids are chemical compounds that are products of secondary metabolism of plants. They are substances of alkaline character because all of them contain at least one nitrogen atom. Most of the alkaloids are N-heterocyclic compounds (sometimes called true alkaloids). We can also find other nitrogen-containing alkaloids, such as alkaloids originating from amino acids (protoalkaloids), peptide and cyclopeptide alkaloids or polyamine alkaloids. Very last group of alkaloid-like substances are compounds that include steroid, purine and terpene-like structures. [1]

The nitrogen atom has major impact on their hydrophobic character. It can also be presumed that they are more hydrophilic than corresponding compounds that do not contain nitrogen atom. The nitrogen atom also allows their frequent interaction with proteins which is the reason for their biological activity. The lone electron pair on nitrogen atom can be an acceptor of proton for hydrogen bond. The protonated nitrogen then can create a bond with the anion groups of receptor in alive organisms. [1]

According to their chemical structure Alkaloids are divided into these groups: Phenylethylamine derivatives

Picture 1- Phenylethylamine Pyrrolidine derivatives

Picture 2 - Pyrrolidine Pyridine derivatives

Picture 3 – Pyridine

Piperidine derivatives

Picture 4 - Piperidine Tropane derivatives

Picture 5 - Tropane Indole derivatives

Picture 6 - Indole Quinoline derivatives

Picture 7 - Quinoline Isoquinoline derivatives

Picture 8 – Isoquinoline

Pyrrolizidine derivatives

Picture 9 – Pyrrolizidine

Quinolizidine derivatives

Picture 10 - Quinolizidine Imidazole derivatives

Picture 11 - Imidazole Tropolone derivatives

Picture 12 - Tropolone Purine derivatives

Picture 13 – Purine

Diterpenes

Steroid derivatives

1.1 History of Alkaloid Chemistry “Modern alkaloid research was initiated by Friedrich Wilhelm Sertürner who was the first able to isolate an alkaloid from a crude natural product. Sertürner was a German pharmacist with a special interest in opium. In 1806 he published a paper in which he described that the “prinzipium somniferum” of opium is an “alkali”, which was later called morphine, although until that time the active principles of crude drugs were thought to be acids. After more than 10 years Sertürner’s discovery led to the isolation of a series of further basic substances from other psychologically active natural products.“ [3]

1.2 Significance of Alkaloid Formation for the Producer Organism Most of the alkaloid compounds are created in plants because of special way of secretion of secondary products. The animals’ unnecessary products of metabolism are released from the body with the urine, bile, sweat and from microbial cells while plants excrete their waste into cells or intracellular spaces such as vacuoles and cell walls. That means that the plants’ bodies can be filled with secondary products of their metabolism. As alkaloids are compounds of generally high toxicity they are usually stored in metabolically non-active parts of cells. Even though, the plants create alkaloids by random process we must take a notice of the fact that many plant alkaloids deter predators and harmful organisms. Their physiological activity is also the reason for their frequent application in medicine. [4]

1.3 Applications Alkaloids are compounds with very wide range of application. While some are substances of great medicinal value others are dangerous poisons or frequently abused drugs.

We can also claim that some abused drugs might have positive effects and are used in psychotherapy or for addiction treatment for example, LSD or psilocybin. Some substances are very addictive and have destructive effects on human brain and body (morphine, heroin and ephedrine derivatives).

These positive and negative effects of drugs will also be further described in corresponding chapters.

2 PHENYLETHYLAMINE DERIVATIVES Phenylaethylamine derivatives are compounds based on the structure:

Picture 14 - Phenylethylamine

The most prominent members of the group are Mescaline, Ephedrine and Norpseudoephedrine.

2.1 Mescaline IUPAC name: 2-(3,4,5-trimethoxyphenyl) ethanamine

Picture 15 - Mescaline Mescaline is a hallucinogenic compound that can be found in peyote cactus Lophophora williamsi.

Picture 16 - Lophophora williamsi

Lophophora williamsi is a “Mexican cactus used in Indian religious rites and as an experimental psychotomimetic. Among its cellular effects are agonist actions at some types of serotonin receptors. Mescaline has no accepted therapeutic uses although it is legal for religious use by members of the Native American Church.” [5]

2.2 Ephedrine and Norpseudoephedrine Ephedrine (IUPAC name: (1R,2S)-2-(methylamino)-1-phenylpropan-1-ol)

Picture 17 - Ephedrine Norpseudoephedrine (IUPAC name: (1R,2R)-2-amino-1-phenylpropan-1-ol)

Picture 18 - Norpseudoephedrine Ephedrine and norpseudoephedrine are compounds that can be found in Ephedra species. An example of Ephedra plant is Ephedra sinica. Ephedra sinica grows in Mongolia, Russia and China.

Picture 19 - Ephedra sinica

Ephedrine has been used as medicament for various diseases and disorders such as, asthma, hearth failure, urinary incontinence, narcolepsy or depression. Ephedrine is very similar in chemical structure to well-known dangerous drug methamphetamine and is often used as a precursor in an illegal production of drugs. [6]

3 PYRIDINE AND PIPERIDINE DERIVATIVES Pyridine derivatives are compounds based on structure:

Picture 20 - Pyridine Piperidine derivatives are based on structure:

Picture 21- Piperidine

3.1 Nicotine IUPAC name: 3-[(2S)-1-methylpyrrolidin-2-yl]pyridine

Picture 22 - Nicotine

Picture 23 - Nicotine 3D structure Nicotine is the most important member of the group. It can be found in leaves of Nicotiana tabacum. It is highly addictive central nervous system stimulant. Nicotine in lower doses causes ganglionic stimulation but in higher doses can be a cause of ganglionic blockage. Nicotine may probably be the most abused drug in the world. [7]

Nicotiana tabacum is a plant originating in subtropical America but because it is cultivated commercially these days it is grown world-widely.

Picture 24 - Nicotiana tabacum Nicotine is usually applicated through inhaling smoke from cigarettes, pipes or cigars. It is highly poisonous especially when it is applicated straight into the blood system. The fatal dose of nicotine is somewhere between 30 and 50 mg. Tabaco smoking provides stimulating effect but has also negative impact on human body. It damages gastric mucosa and the haemoglobin-oxygen bondage. Certain part of haemoglobin is blocked by carbon monoxide. It has also been proved that smokers are much more likely to be diagnosed with lung cancer. [8]

3.1.1 Nicotine isolation [8] Chemicals and materials: calcium hydroxide (water solution), potassium iodide solution, picric acid (concentrated), sodium hydroxide (20% water solution), ice, cigarette tobacco, Erlenmeyer flask, plug, glass tube, test-tube, heating circle, iron reticle, matches, gas burner, boiling flask, Claisen adapter, cooler, allonge, beakers, cooling tubes, scissors, morter.

Working process A:

1) Put about 3-5 grams of ground tobacco into Erlenmeyer flask. Add calcium water and stir for about 5 minutes to get the maxim contact of the water and the tobacco. 2) Close the flask. Use the plug with hole and put through the glass tube. The glass tube should lead to a test-tube. The test-tube should be cooled from its bottom. (Use a beaker or container filled with ice-cold water.

3) When the equipment is prepared turn on the gas burner and heat the mixture until you get about 20 ml of the distillate. The distillate contains nicotine. 4) Focus on the colour and the smell of the distillate. 5) Put 1 ml of the distillate to a pure test-tube. Add 3 drops of potassium iodide solution. Watch the black/brown precipitate which is slowly dissolved. 6) Put 1 ml of the distillate to another pure test-tube and add 4 drops of picric acid. Watch the yellow precipitate which slowly dissolved in the redundancy of nicotine solution. 7) Explain the results.

Working process B:

1) Set up a classic distillation equipment. 2) Put 3-5 grams of ground tobacco into a boiling flask and add 25 ml of sodium hydroxide (20% water solution). 3) Turn on the gas burner and start heating. Be careful not to burn the tobacco. 4) Heat until there is 10 ml of distillate. 5) Make the same experiments as in A.

3.2 Coniine IUPAC name: (2S)-2-propylpiperidine

Picture 25 - Coniine

Picture 26 - Coniine 3D structure

Coniine is a very poisonous compound found in Conium maculatum. It is mostly famous for the fact that it was coniine that Socrates was poisoned with.

Conium maculatum is a poisonous plant from the carrot family Apiaceae. It grows in Europe and North Africa.

Picture 27 - Conium maculatum

4 PYRROLIDINE DERIVATIVES Pyrrolidine derivatives are compounds based on the following structure:

Picture 28 - Pyrrolidine We will only discuss the two most prominent members of the pyrrolidine group. These two members are two alkaloids hygrine and cuscohygrine. They can be found in leaves of Erythroxylon coca. They often accompany tropane alkaloids and are even similar in structure.[1]

Picture 29 - Erythroxylon coca ‘’Erythroxylon coca is a high altitudes S. American shrub that's leaves are the source of cocaine. The leaves are "chewed" (held in the cheek) in combination with mineral lime to provide physical and mental stimulation and reduction in altitude sickness. It has a long history of human use.’’ [9]

4.1 Hygrine IUPAC name: 1-[(2R)-1-methylpyrrolidin-2-yl]propan-2-one

Picture 30 - Hygrine

Picture 31 - Hygrine 3D structure

4.2 Cuscohygrine IUPAC name: 1-(1-methylpyrrolidin-2-yl)-3-[(2S)-1-methylpyrrolidin-2-yl]propan-2- one

Picture 32 - Cuscohygrine

Picture 33 - Cuscohygrine 3D structure

5 TROPANE DERIVATIVES Tropane is a compound with the following structure:

Picture 34 - Tropane Even though, the group is named after tropane the tropane alkaloids are in fact derivatives of 8-azabicyclo[3,2,1]octane that is sometimes called nortropane.

Picture 35 - Nortropane All the tropane alkaloids are sometimes regarded as members of piperidine and pyrrolidine group. That is caused by the fact that we can often find those structures in the tropane group compounds. There are two subgroups in the tropane group. The first subgroup is an atropine group. Atropine group is based on tropine. Tropine has an axial -OH group in position three. The other group is a pseudotropine group that has an equatorial -OH group in position three. [1]

5.1 Atropine group The most significant members of the group are atropine, hyoscyamine and scopolamine. All three of them are found in plants of Solanaceae family. [1]

5.1.1 Atropine IUPAC name:

[(1R,5S)-8-methyl-8-azabicyclo[3.2.1]octan-3-yl] 3-hydroxy-2-phenylpropanoate

Picture 36 - Atropine

Picture 37 - Atropine 3D structure Atropine is an alkaloid compound found in plant Atropa bella-donna.

Picture 38 - Atropa bella-donna 23

Atropine is also mentioned in books written by Agatha Christie who used the poison to kill characters in her stories. Agatha Christie was a chemists and toxicologist and killed off about 300 characters in her books with poisons.

‘’I remember John explaining how women in olden days used belladonna juice to dilate the pupils of the eye, to make themselves more attractive.

Atropine, the deadly nightshade derivative, is still used today by ophthalmologists. But while it is safe as eyedrops, if ingested and absorbed through the mucus membranes, it is curtains: rapid pulse, hot skin, muscular stiffness, delirium and eventually death.’’ [10]

5.1.2 Hyoscyamine IUPAC name:

[(1S,5R)-8-methyl-8-azabicyclo[3.2.1]octan-3-yl] (2S)-3-hydroxy-2-phenylpropanoate

[1] Hyoscyamine is the levorotatory form of racemic atropine. It can be found in Atropa bella-donna or Hyoscyamus niger. Hyoscyamus niger is a poisonous plant that is grown in Europe and India.

Picture 39 - Hyoscyamus niger Hyoscyamine is ‘’used to treat mild to moderate nausea, motion sickness, hyperactive bladder and allergic rhinitis.’’ [11]

5.1.3 Scopolamine IUPAC name:

(–)-(S)-3-Hydroxy-2-phenylpropionic acid (1R,2R,4S,7S,9S)-9-methyl-3-oxa-9- azatricyclo[3.3.1.0(2,4)]non-7-yl ester

Picture 40 - Scopolamine

Picture 41 - Scopolamine 3D structure Scopolamine is also often called hyoscine. In high concentration it can be found in Datura stramonium.

Picture 42 - Datura stramonium

5.2 Pseudotropine group Pseudotropine compounds have the -COOH group in the position two. The compounds we will be talking about are: ecgonine, pseudoecgonine and cocaine. All these compounds can be found in leaves of Erythroxylon coca.

Picture 43 - Erythroxylon coca

5.2.1 Ecgonine IUPAC name:

(1S,3S,4R,5R)-3-hydroxy-8-methyl-8-azabicyclo[3.2.1]octane-4-carboxylic acid

Picture 44 – Ecgonine 5.2.2 Pseudoecgonine IUPAC name:

(1S,3S,4R,5R)-3-hydroxy-8-methyl-8-azabicyclo[3.2.1]octane-4-carboxylic acid

Obrázek 45 – Pseudoecgonine

5.2.3 Cocaine IUPAC name: methyl (1S,3S,4R,5R)-3-benzoyloxy-8-methyl-8-azabicyclo[3.2.1]octane-4-carboxylate

Picture 46 - Cocaine Cocaine is an ecgonine derivate. The -OH group of ecgonine is esterified with methyl group and also -COOH group is esterified with benzoic acid. [1]

Cocaine is an illegal drug with locally anesthetic effect and centrally stimulating effect. It is also highly addictive due to its reward pathway in the human brain. More than 90 % of cocaine is illegally produced in Colombia and then trafficked to either North America or to Europe. That is the reason for its high price on the black market. The cocaine bought on the street is usually mixed with other chemicals because the dealers want to make higher profit. This makes the cocaine abuse even more dangerous. Due to its high price, cocaine is popular among businessmen and stock brokers who use the drug to cope better with stress in everyday life. Cocaine also used to be used for its numbing effect in dental surgery.

The effects of the drug are happiness, euphoria, increased self-confidence, higher blood pressure, fast hearth rate, sweating and higher body temperature.

Cocaine had its time of fame in 1980´s when most Hollywood celebrities were taking it. Famous people who are known for cocaine use are for example: Stephen King, Angelina Jolie, Whitney Houston, Thomas Edison, Sigmund Freud and thousands of others.

What people usually find very surprising is the fact that cocaine was a popular drug among first-republican actors in our country. Hugo Hass, Adina Mandlová, Lída Baarová, Otakar Vávra, Ljuba Hermanová and others are still remembered for their passion for cocaine.

According to the Czech police statistics, there were 120375 grams of cocaine seized in 2015 in the Czech Republic. [12]

6 INDOLE DERIVATVES Indole derivatives are based on the following structure:

Picture 47 - Indole But sometimes the indole molecule is only a small part of more complex structures. Because of that we will simply divide indole derivatives into simple and complex ones. Simple compounds that will be further described are gramine, bufotenine and psilocybine. The complex ones are so called cockle alkaloids yohimbine, fysostigmine, reserpine and strychnine. Other compounds that are worth of more detailed description are lysergic acid and LSD.

6.1 Simple-structured compounds 6.1.1 Gramine IUPAC name: 1-(1H-indol-3-yl)-N,N-dimethylmethanamine

Picture 48 – Gramine

Picture 49 - Gramine 3D structure

Gramine can possibly play a role of repeller in many plants because of its toxicity to many organisms. It can be isolated from Arundo donax.

Picture 50 - Arundo donax

6.1.2 Bufotenine IUPAC name: 3-[2-(dimethylamino)ethyl]-1H-indol-5-ol

Picture 51 - Bufotenine

Picture 52 - Bufotenine 3D structure Bufotenine is a hallucinogenic compound with analogism to serotonin. It is found in skins of frogs or tods but also in mushrooms, higher plants and even in human brains. It has also been used as a tool in a research of central nervous system.

An example of bufotenine containing organism is Bufo vulgaris.

Picture 53 - Bufo vulgaris

6.1.3 Psilocybine IUPAC name: [3-[2-(dimethylamino)ethyl]-1H-indol-4-yl] dihydrogen phosphate

Picture 54 - Psilocybine

Picture 55 - Psilocybine 3D structure

Psilocybine is one of the two major hallucinogenic compounds contained in so called psychoactive mushrooms. The examples of the producer organisms are Psilocybe mexicana and Psilocybe bohemica.

Picture 56 - Psilocybe mexicana

Picture 57 - Psilocybe bohemica

‘’Serotonin, psilocin and psilocybin are basic alkaloids derived from these mushrooms. They are powerful psychoactive and neurotransmitter compounds. Recreational use of hallucinogenic mushrooms has been reported in several European countries, including England, Norway, Finland, the Netherlands and Germany’’ [13]

6.2 Complex-structured compounds 6.2.1 Yohimbine IUPAC name: methyl (1S,15R,18S,19R,20S)-18-hydroxy-1,3,11,12,14,15,16,17,18,19,20,21- dodecahydroyohimban-19-carboxylate

Picture 58 - Yohimbine Yohimbine is a plant alkaloid that has been used in treatment of erectile dysfunction.

6.2.2 Physostigmine IUPAC name:

[(3aR,8bS)-3,4,8b-trimethyl-2,3a-dihydro-1H-pyrrolo[2,3-b]indol-7-yl] N- methylcarbamate

Picture 59 – Physostigmine

Physostigmine is a plant alkaloid isolated from Physostigma venenosum.

Picture 60 - Physostigma venenosum

6.2.3 Reserpine IUPAC name: methyl (1R,15S,17R,18R,19S,20S)-6,18-dimethoxy-17-(3,4,5-trimethoxybenzoyl)oxy- 1,3,11,12,14,15,16,17,18,19,20,21-dodecahydroyohimban-19-carboxylate

Picture 61 – Reserpine

Reserpine was isolated from different kinds of Rauwolfie.

Picture 62 - Rauvolfia serpentine

6.2.4 Strychnine IUPAC name:

4a,5,5a,7,8,13a,15,15a,15b,16-decahydro-2H-4,6-methanoindolo[3,2,1- ij]oxepino[2,3,4-de]pyrrolo[2,3-h]quinoline-14-one

Picture 63 - Strychnine “It has been used as an analeptic, in the treatment of nonketotic hyperglycaemia and sleep apnea, and as a rat poison.” [13]

6.3 Lysergic acid IUPAC name:

(6aR,9R)-7-methyl-6,6a,8,9-tetrahydro-4H-indolo[4,3-fg]quinoline-9-carboxylic acid

Picture 64 - Lysergic acid Lysergic acid is famous for its derivative LSD. LSD is a synthetic compound with strong hallucinogenic effect. LSD was very popular among hippies in 1960´s.

Picture 65 - LSD papers These days scientists start to realise the potential of the drug and many researches start revealing possible use of the drug in psychology, therapy and in addiction treatment.

The Guardian describes the effects of LSD in the article from 2016: ‘’The effect could underpin the altered state of consciousness long linked to LSD, and the sense of the self-disintegrating and being replaced with a sense of oneness with others and nature. “This experience is sometimes framed in a religious or spiritual way, and seems to be associated with improvements in wellbeing after the drug’s effects have subsided,” Carhart-Harris said.

The drug can be seen as reversing the more restricted thinking we develop from infancy to adulthood, said Nutt, whose study appears in the journal Proceedings of the National Academy of Sciences.

The study could pave the way for LSD or related chemicals to be used to treat psychiatric disorders. Nutt said the drug could pull the brain out of thought patterns seen in depression and addiction through its effects on brain networks.

Amanda Feilding, director of the Beckley Foundation, said: “We are finally unveiling the brain mechanisms underlying the potential of LSD, not only to heal, but also to deepen our understanding of consciousness itself.” ‘’ [15]

7 QUINOLINE DERIVATIVES Quinoline derivatives are compounds based on the following structure:

Picture 66 - Quinoline The most important members of the group are compounds isolated from bark of Cinchona from the botanical family Rubiceae. These compounds are quinine, quinidine, cinchonidine and cinchonine. An example of a Cinchona plant is Cinchona officinalis.

Picture 67 - Cinchoma officinalis

7.1 Quinine IUPAC name:

(R)-[(2S,5R)-5-ethenyl-1-azabicyclo[2.2.2]octan-2-yl]-(6-methoxyquinolin-4- yl)methanol

Picture 68 – Quinine Quinine is the compound with the biggest possible application in medicine. It has been used as an anti-malaria cure and is also added to many cold pills for its anti- pyretic effect. Most people know quinine for it being an added ingredient in bitter beverages (tonic). As quinine is a plasmatic poison, pregnant women should avoid drinking tonic and other quinine containing beverages.

7.2 Qunidine IUPAC name:

(S)-[(2R,4S,5R)-5-ethenyl-1-azabicyclo[2.2.2]octan-2-yl]-(6-methoxyquinolin-4- yl)methanol

Picture 69 - Quinidine Quinidine is an optical isomer of quinine. It is used to cure hearth arrhythmia for its antiarrhythmic effect. Quinidine as well as quinine is a part of antimalarial pills.

8 ISOQUINOLINE DERIVATIVES Isoquinoline group compounds are based on the following structure:

Picture 70 - Isoquinoline Isoquinoline group is probably the most numerous group of alkaloids. Most compounds were isolated from opium which is a juice extracted from unripe poppy seed plant. In this chapter we will further describe papaverine, laudanosine, hydrastine and morphine group. Morphine group is the most important for its wide pharmaceutical use. The compounds of the morphine group that will be described in detail are morphine, codeine and thebaine.

Opium poppy (Papaver somniferum)

Picture 71 - Papaver somniferum

Picture 72 - Opium

8.1.1 Papaverine IUPAC name: 1-[(3,4-dimethoxyphenyl)methyl]-6,7-dimethoxyisoquinoline

Picture 73 - Papaverine Papaverine is a synthetically made compound that is important for its medicinal effect. It is a smooth muscle relaxant and is used to treat impotence.

8.1.2 Laudanosine IUPAC name:

1-[(3,4-dimethoxyphenyl)methyl]-6,7-dimethoxy-2-methyl-3,4-dihydro-1H- isoquinoline

Picture 74 - Laudanosine Laudanosine is a natural alkaloid that is found in opium but only in very low amounts (2-12 %). It is very closely related to papaverine as there are similarities in chemical structure. It is used to treat vasospasm but overall does not have a big potential in medicine.

8.1.3 Hydrastine IUPAC name:

6,7-dimethoxy-3-(6-methyl-7,8-dihydro-5H-[1,3]dioxolo[4,5-g]isoquinolin-5-yl)-3H-2- benzofuran-1-one

Picture 75 - Hydrastine Hydrastine is a natural alkaloid that is not found in opium but was isolated from the roots of Hydrastis canadensis. Hydrastine does not have a big medicinal value.

Picture 76 - Hydrastis Canadensis

8.1.4 Reticuline IUPAC name:

1-[(3-hydroxy-4-methoxyphenyl)methyl]-6-methoxy-2-methyl-3,4-dihydro-1H- isoquinolin-7-ol

Picture 77 - Reticuline Reticuline is an important intermediate product in the morphine alkaloid biosynthesis in plants.

Picture 78 - Reticuline x Morphine – The picture is based on [2]

8.2 Morphine group The morphine group is pharmaceutically very important. The three most important members of the group are morphine, codeine and thebaine. All of them are found in opium. The content of morphine oscillates in range 3-23 %, codeine 0,3-3 % and thebaine in 0,2-1 %. Procedures that enabled changing one morphine alkaloid into another have been discovered. [1]

8.2.1 Morphine IUPAC name:

(4R,4aR,7S,7aR,12bS)-3-methyl-2,4,4a,7,7a,13-hexahydro-1H-4,12- methanobenzofuro[3,2-e]isoquinoline-7,9-diol

Picture 79 - Morphine The content of morphine in opium ranges in 3-23 %. During the morphine biosynthesis reticuline is changed into thebaine which is then transformed into morphine. This is also the reason why all three compounds together are found in opium. [1]

Morphine was first isolated by doctor Sertürner in between years 1803 and 1806. Doctor Sertürner also became the first victim of morphine addiction.

Morphine acts directly on central nervous system and decreases the feeling of pain. It also provides strong euphoric effect which is a reason for it being abused all over the world. Through the process of acetylation, morphine can be changed into heroine which provides even stronger euphoric effect. The use of morphine and heroin causes physical and psychical problems.

Picture 80 - Morphine (left) vs. Heroin (right)

Celebrities like Angelina Jolie, Keith Richards, Kurt Cobain, Eric Clapton and hundreds of others are known for their heroin addiction.

According to the Czech police statistics, there were 1562 grams of heroin seized in the Czech Republic in 2015. [12]

8.2.2 Codeine IUPAC name:

(4R,4aR,7S,7aR,12bS)-9-methoxy-3-methyl-2,4,4a,7,7a,13-hexahydro-1H-4,12- methanobenzofuro[3,2-e]isoquinoline-7-ol

Picture 81 - Codeine Codeine is not as addictive as heroine or morphine because it does not provide that strong euphoric effect. Codeine is still used as an ingredient for cough syrups for its antitussive effect. The content of codeine in opium is 0,3-3 %.

8.2.3 Thebaine IUPAC name:

(4R,7aR,12bS)-7,9-dimethoxy-3-methyl-2,4,7a,13-tetrahydro-1H-4,12- methanobenzofuro[3,2-e]isoquinoline

Picture 82 - Thebaine The content of thebaine in opium is 0,2-1 %.

8.3 Other isoquinoline derivatives 8.3.1 Berberine IUPAC name:

9,10-Dimethoxy-5,6-dihydro[1,3]dioxolo[4,5-g]isoquinolino[3,2-a]isoquinolin-7-ium

Picture 83 - Berberine Berberine was first isolated from Berberis vulgaris. Berberine is used to treat various fungal and parasitic infections. One of the most important researchers of berberine related compounds is a Czech professor Vilím Šimánek. [1]

Picture 84 - Berberis vulgaris

8.3.2 Tubocurarine

Picture 85 - Turbocurarine [1] Tubocurarine is found in plant family Chondrodendron. Tubocurarine is used by South American Indians. They use it to poison the tips of their arrows. Tubocurarine is a neuromuscular blocker but has no effect at all when it is used orally.

Picture 86 - Chondronendron platiphyllum

9 PYRROLIZIDINE DERIVATIVES Pyrrolizidine group compounds are based on the following structure:

Picture 87 - Pyrrolizidine Many pyrrolizidine derivatives are located in plants, namely in species Senecio, Erechtites and Crotalaria. They are not medically too important due to their relatively high toxicity. An example of a Senecio group plant is Senecio barbertonicus. An example of Erechtites plant is Erechtites minima. An example of a Crotalaria plant is Crotalaria retusa.

Picture 88 - Senecio barbertonicus

Picture 89 - Erechtites minima

Picture 90 - Crotalaria retusa

9.1 Monocrotaline

Picture 91 - Monocrotaline Monocrotaline is an alkaloid poison that can occasionally poison livestock or humans through contaminated grains in food.

10 QUINOLIZIDINE DERIVATIVES Quinolizidine group is based on the following structure:

Picture 92 - Quinolizidine There are three interesting compounds in this group that we will take a closer look at. These compounds are lupinine, sparteine and emetine.

10.1 Lupinine IUPAC name: [(1R,9aR)-2,3,4,6,7,8,9,9a-octahydro-1H-quinolizin-1-yl]methanol

Picture 93 - Lupinine Lupinine was isolated from Lupinus luteus.

Picture 94 - Lupinus luteus

The variety that is grown in the Czech republic is Lupinus polyphyllus.

Picture 95 - Lupinus polyphyllus

10.2 Emetine IUPAC name:

(2S,3R,11bS)-2-[[(1R)-6,7-dimethoxy-1,2,3,4-tetrahydroisoquinolin-1-yl]methyl]-3- ethyl-9,10-dimethoxy-2,3,4,6,7,11b-hexahydro-1H-benzo[a]quinolizine

Picture 96 - Emetine

Emetine was isolated from Carapichea ipecacuanha.

Picture 97 - Carapichea ipecacuanha

10.3 (-)-Sparteine IUPAC name: (6R,8S,10R,12S)-7,15-diazatetracyclo[7.7.1.02,7.010,15]heptadecane

Picture 98 - (-)-Sparteine

Sparteine was isolated from Sarothamnus scoparius.

Picture 99 - Sarothamnus scoparius

11 IMIDAZOLE DERIVATIVES Imidazole derivatives are compounds based on the following structure:

Picture 100 - Imidazole The most prominent members of the group are pilocarpine and muscarine.

11.1 Pilocarpine IUPAC name: (3S,4R)-3-ethyl-4-[(3-methylimidazol-4-yl)methyl]oxolan-2-one

Picture 101 - Pilocarpine Pilocarpine was isolated from a South American plant Pilocarpus jaborandi. It is known for its cholinergic effect. It has also been used to cure glaucoma.

Picture 102 - Pilocarpus jaborandi

11.2 Muscarine IUPAC name: [(2S,4R,5S)-4-hydroxy-5-methyloxolan-2-yl]methyl-trimethylazanium

Picture 103 - Muscarine Muscarine was isolated mainly from Amanita muscaria.

Picture 104 - Amanita muscaria

12 PURINE DERIVATIVES Purine derivatives are based on the following structure:

Picture 105 - Purine The first compound we will describe is xanthine. Even though xanthine is not a natural alkaloid we think it is important to be mentioned as it is an intermediate product in biosynthesis of purine nucleic bases.

The proper members of the purine alkaloid group are theophylline, theobromine and caffeine. Caffeine alongside with theophylline and theobromine is found in coffee, cocoa and tea plants.

12.1 Xanthine IUPAC name: 3,7-Dihydro-1H-purine-2,6-dione

Picture 106 - Xanthine Its methylderivatives are found in plants and create a group of proper purine alkaloids.

12.2 Theophylline IUPAC name: 1,3-dimethyl-7H-purine-2,6-dione

Picture 107 - Theophylline Theophylline is commonly used as a cure for asthma and chronic obstructive pulmonary disease.

12.3 Theobromine IUPAC name: 3,7-dimethylpurine-2,6-dione

Picture 108 - Theobromine Theobromine is an alkaloid found mainly in cocoa plant (Theobroma cacao). The cocoa plant was originally grown in tropical part of South America but later on was spread all over the world. These days the biggest plantations are found in Ghana, Brazil and Nigeria.

Picture 109 - Theobroma cacao

Picture 110 - Cocoa beans Cocoa powder as we know it is made out of cocoa beans through a process that involves about 6 days of fermentation. Fermentation requires high temperatures and use of acetic acid. After the process of fermentation cocoa beans need to be dried under temperatures between 80 and 130 °C. When the beans are dried they are ground. The next step means separation of cocoa mass and cocoa butter through the process of pressing. The two products we have are cocoa butter and cocoa powder that are both used for making chocolate.

12.4 Caffeine IUPAC name: 1,3,7-trimethylpurine-2,6-dione

Picture 111 - Caffeine Caffeine has a light stimulatory effect. It has an impact on hearth functions and on central nervous system. It also has a diuretic effect. Even though, it is not very addictive, it is often classified as a drug. Caffeine addiction is also sometimes called caffeinism. [8]

Caffeine is most of the time isolated from coffee beans which are cherries of a coffee plant. The two most prominent kinds are Coffea arabica and Coffea robusta.

Coffea arabica origins in Africa, most probably the area of today´s Ethiopia. Arabica contains less caffeine but has much better flavours. When drinking Arabica one should sense more acidic and sweet flavours that are generally milder than the flavours in robusta. Arabica is these days grown in tropical areas of Colombia, Brazil, Ethiopia, Kenya and Indonesia. [16]

Picture 112 - Coffea arabica

Picture 113 - Arabica beans Coffea robusta origins in western sub-Saharan Africa but is grown mostly in Vietnam and India. The coffee beans of robusta contain more caffeine than beans of arabica but have strong and bitter flavour that is not as appreciative as arabica. Robusta is generally easier to be grown and gives bigger harvests than arabica which is the reason for it being used in cheaper coffee mixtures that are sold in supermarkets. [16]

Picture 114 - Coffea robusta

Picture 115 - Robusta beans 59

The difference between the shape of the beans is enormous. While arabica has two beans in one cherry, robusta only has one. This means that robusta has round beans but arabica has semi-circular shaped beans. [16]

Apart from being present in coffee plants, caffeine can also be isolated from tea plants. The tea plants (Camellia sinensis) has two major varieties. Variety sinensis is a Chinese tea variety and variety assamica is a variety of Indian Assam teas. Tea can also be subdivided according to the degree of their fermentation. Green tea is only lightly fermented whereas black tea goes through a longer process of fermentation.

Picture 116 - Camellia sinensis

12.5 Caffeine microsublumation [8] Materials: 2 grams of freshly ground coffee, ice, porcelain bowl, slide glass, burning ring, stand, gas burner, matches, chemical spoon and microscope.

Working process:

1) Place the ground coffee into the middle part of the porcelain bowl. 2) Put the microscopic slide glass on the bowl and place a cube of ice on the top side of the glass. 3) Put the gas burner under the bowl. (Use burning ring for the bowl). 4) Start heating the bowl but be careful so that the coffee does not start burning or smoking. Heat for about 5 minutes. 5) Stop the burner and carefully remove the microscopic slide glass from the bowl. Turn the glass the bottom side up and microscope. (Wipe the upper part of the slide glass if necessary). 6) Microscope the needle-like crystals of caffeine.

13 STEROIDAL ALKALOIDS Some alkaloids found in plant families Liliaceae, Solanaceae, Buxaceae are based on a steroidal structure. They are aglycones in glycosides. Examples of the steroidal alkaloids are solanidine, rubijervine and tomatidine.

13.1 Solanidine

Picture 117 - Solanidine

13.2 Rubijervine

Picture 118 - Rubijervine

13.3 Tomatidine

Picture 119 - Tomatidine

13.4 Proof of solanine presence in potatoes [8] Chemicals and materials: Concentrated sulfuric acid, acetic acid, formaldehyde (1% water solution), hydrogen peroxide (0,5%), potatoes (with green skin), Petri dish, 4 micropipettes, knife, tweezers, paper filter, microscope, slide glass.

Working process:

1) Make four thin cuts of potatoes and place them either into the Petri dish or on the slide glass. 2) Drop 3 drops of sulfuric acid on the first slice, acetic acid on the second, formaldehyde on the third and hydrogen peroxide on the last slice. 3) The presence of solanine appears through red colour stains. 4) Describe the colour and its intensity of each slice.

14 DITERPENE ALKALOIDS These days about 500 diterpene alkaloids have been described. They are often compounds of different complex and complicated structures. Some are regarded as very dangerous poisons. Studies concerning their pharmacological character has recently been started. An example of a diterpene alkaloid is aconitine.

14.1 Aconitine

Picture 120 - Aconitine

Aconitine was isolated from Aconitum firmum.

Picture 121 - Aconitum firmum

Its Czech relative is Aconitum plicatum.

Picture 122 - Aconitum plicatum

15 TROPOLONE DERIVATIVES Tropolone derivatives are based on the following structure:

Picture 123 - Tropolone

15.1 Colchicine IUPAC name:

N-[(7S)-1,2,3,10-tetramethoxy-9-oxo-6,7-dihydro-5H-benzo[a]heptalen-7-yl]acetamide

Picture 124 - Colchicine Colchicine was isolated from Colchicum autumnale. It is highly toxic compound but in milligram doses has been used in treatment of goaty arthritis.

Picture 125 - Colchicum autumnale 65

CONCLUSION The aims of the thesis have been achieved. A textbook called Introduction to Alkaloids has been created. The study material was created in a way that should attract students to study more about the important group of natural compounds – Alkaloids. At the same time, the study material should suit perfectly to non-native speakers of English and should not cause any trouble to those who find reading in English difficult.

Alkaloids were divided into 15 chapters according to their chemical structure. The thesis contains text and 125 pictures. Every compound that has been described is also connected with its chemical formula. The chemical formulas were drawn in the Chemsketch program by the author himself. All the other pictures were downloaded from free internet sources.

Sources used 1. WAISSER, Karel a Karel PALÁT. Bioorganická chemie. 2. přeprac. vyd. Praha: Karolinum, 2001. ISBN 80-246-0382-9. 2. HENRY, Thomas Anderson. The plant alkaloids. 4. edition. London: J., 1949.The Plant Alkaloids. 3. MOTHES, Kurt, Horst Robert SCHÜTTE a Martin LUCKNER, ed. Biochemistry of alkaloids. Berlin: Deutscher Verlag der Wissenschaften, 1985. (str.15) 4. MOTHES, Kurt, Horst Robert SCHÜTTE a Martin LUCKNER, ed. Biochemistry of alkaloids. Berlin: Deutscher Verlag der Wissenschaften, 1985. 5. Pubchem [online]. 8600 Rockville Pike, Bethesda, MD20894, USA: U.S. National Library of Medicine, 2005 [cit. 2017-03-22]. Dostupné z: https://pubchem.ncbi.nlm.nih.gov/compound/mescaline#section=Top 6. Pubchem [online]. 8600 Rockville Pike, Bethesda, MD20894, USA: U.S. National Library of Medicine, 2004 [cit. 2017-03-22]. Dostupné z: https://pubchem.ncbi.nlm.nih.gov/compound/Ephedrine#section=Top 7. Pubchem [online]. 8600 Rockville Pike, Bethesda, MD20894, USA: U.S. National Library of Medicine, 2004 [cit. 2017-03-22]. Dostupné z: https://pubchem.ncbi.nlm.nih.gov/compound/nicotine#section=Top 8. ŠIBOR, Jiří a Hana CÍDLOVÁ. Praktická cvičení z biochemie a bioorganické chemie. 1. vydání. Brno: Masarykova univerzita v Brně, 2005. 49 s. ISBN 80- 210-3883-7. 9. Erowid [online]. 2016 [cit. 2017-03-22]. Dostupné z: https://erowid.org/plants/coca/ 10. Daily mail: Cripes! Did someone give him a fig-paste sandwich? A brilliant study of the poisons Agatha Christie used to kill off characters [online]. 2015 [cit. 2017-03-22]. Dostupné z: http://www.dailymail.co.uk/home/books/article- 3229892/Cripes-Did-fig-paste-sandwich-brilliant-study-poisons-Agatha- Christie-used-kill-characters.html#ixzz4bnmgDzX0 11. Pubchem [online]. 8600 Rockville Pike, Bethesda, MD20894, USA: U.S. National Library of Medicine, 2005 [cit. 2017-03-22]. Dostupné z: https://pubchem.ncbi.nlm.nih.gov/compound/154417#section=Top

12. Úřad vlády České republiky. (2016). Výroční zpráva o stavu ve věcech drog v České republice v roce 2015: Česká republika. Praha: Úřad vlády ČR. [cit. 2017- 03-22] Dostupné z: https://www.drogy- info.cz/data/obj_files/32232/741/VZ_2015_drogova_situace_v_CR_v02.pdf 13. ANISZEWSKI, Tadeusz. Alkaloids - secrets of life: alkaloid chemistry, biological significance, applications and ecological role. Boston: Elsevier, 2007. ISBN 978-0-444-52736-3. (str. 54) 14. Pubchem [online]. 8600 Rockville Pike, Bethesda, MD20894, USA: U.S. National Library of Medicine, 2005 [cit. 2017-03-22]. Dostupné z: https://pubchem.ncbi.nlm.nih.gov/compound/5304#section=Top 15. The Guardian: LSD's impact on the brain revealed in groundbreaking images [online]. 2016 [cit. 2017-03-22]. Dostupné z: https://www.theguardian.com/science/2016/apr/11/lsd-impact-brain-revealed- groundbreaking-images 16. VESELÁ, Petra. Kniha o kávě: průvodce světem kávy s recepty na její přípravu. Praha: Smart Press, 2010. ISBN 978-80-87049-34-1.

Pictures and their sources 1. Picture 1 - Phenylethylamine 2. Picture 2 – Pyrrolidine 3. Picture 3 – Pyridine 4. Picture 4 – Piperidine 5. Picture 5 – Tropane 6. Picture 6 – Indole 7. Picture 7 – Quinoline 8. Picture 8 – Isoquinoline 9. Picture 9 - Pyrrolizidine 10. Picture 10 – Quinolizidine 11. Picture 11 – Imidazole 12. Picture 12 – Tropolone 13. Picture 13 – Purine 14. Picture 14 – Phenylethylamine 15. Picture 15 – Mescaline 16. Picture 16 – Lophophora williamsi, Dostupné z: https://upload.wikimedia.org/wikipedia/commons/0/05/Lophophora-williamsii- costapppr.jpg [cit. 2017-03-28] 17. Picture 17 – Ephedrine 18. Picture 18 – Norpseudoephedrine 19. Picture 19 – Ephedra sinica, Dostupné z: https://commons.wikimedia.org/wiki/File:Ephedra_viridis_5.jpg [cit. 2017-03-28] 20. Picture 20 – Pyridine 21. Picture 21 – Piperidine 22. Picture 22 – Nicotine 23. Picture 23 – Nicotine 3D structure 24. Picture 24 – Nicotiana tabacum, Dostupné z: https://commons.wikimedia.org/wiki/File:P1000484_Nicotiana_tabacum_(tobacc o)_(Solanaceae)_Flower.JPG [cit. 2017-03-28] 25. Picture 25 - Coniine 26. Picture 26 – Coniine 3D structure

27. Picture 27 – Conium maculatum, Dostupné z: https://commons.wikimedia.org/wiki/File:Conium_maculatum_- _K%C3%B6hler%E2%80%93s_Medizinal-Pflanzen-191.jpg [cit. 2017-03-28] 28. Picture 28 - Pyrrolidine 29. Picture 29 – Erythroxylon coca, Dostupné z: https://upload.wikimedia.org/wikipedia/commons/e/ea/Flickr_- _Jo%C3%A3o_de_Deus_Medeiros_-_Erythroxylum_citrifolium.jpg [cit. 2017-03-28] 30. Picture 30 - Hygrine 31. Picture 31 – Hygrine 3D structure 32. Picture 32 – Cuscohygrine 33. Picture 33 – Cuscohygrine 3D structure 34. Picture 34 - Tropane 35. Picture 35 - Nortropane 36. Picture 36 – Atropine 37. Picture 37 – Atropine 3D structure 38. Picture 38 - Atropa bella-donna, Dostupné z: https://simple.wikipedia.org/wiki/Deadly_nightshade#/media/File:Atropa_bellad onna_-_K%C3%B6hler%E2%80%93s_Medizinal-Pflanzen-018.jpg [cit. 2017-03-28] 39. Picture 39 – Hyoscyamus niger, Dostupné z: https://commons.wikimedia.org/wiki/File:Hyoscyamus_niger_- _K%C3%B6hler%E2%80%93s_Medizinal-Pflanzen-073.jpg [cit. 2017-03-28] 40. Picture 40 - Scopolamine 41. Picture 41 – Scopolamine 3D structure 42. Picture 42 – Datura stramonium, Dostupné z: https://ca.wikipedia.org/wiki/Estramoni#/media/File:DATURA_STRAMONIUM _-_GUIXERS_-_IB-615.JPG [cit. 2017-03-28] 43. Picture 43 – Erythroxylon coca, Dostupné z: https://upload.wikimedia.org/wikipedia/commons/e/ea/Flickr_- _Jo%C3%A3o_de_Deus_Medeiros_-_Erythroxylum_citrifolium.jpg [cit. 2017- 03-28] 44. Picture 44 - Ecgonine

45. Picture 45 - Pseudoecgonine 46. Picture 46 - Cocaine 47. Picture 47 - Indole 48. Picture 48 - Gramine 49. Picture 49 – Gramine 3D structure 50. Picture 50 – Arundo donax, Dostupné z: https://ca.wikipedia.org/wiki/Fitxer:Illustration_Arundo_donax0.jpg [cit. 2017-03-28] 51. Picture 51 - Bufotenine 52. Picture 52 – Bufotenine 3D structure 53. Picture 53 – Bufo vulgaris, Dostupné z: https://simple.wikipedia.org/wiki/Common_toad#/media/File:Bufo_bufo_sitting- Iric2006.jpg [cit. 2017-03-28] 54. Picture 54 - Psilocybine 55. Picture 55 – Psilocybine 3D structure 56. Picture 56 – Psilocybe Mexicana, Dostupné z: https://commons.wikimedia.org/wiki/File:Psilocybe_mexicana_53966.jpg [cit. 2017-03-28] 57. Picture 57 – Psilocybe bohemica, Dostupné z: https://commons.wikimedia.org/wiki/File:Psilocybe.bohemica.gkoller.jpg [cit. 2017-03-28] 58. Picture 58 - Yohimbine 59. Picture 59 - Physostigmine 60. Picture 60 – Physostigma venenosum, Dostupné z: https://commons.wikimedia.org/wiki/File:Physostigma_venenosum_- _K%C3%B6hler%E2%80%93s_Medizinal-Pflanzen-237.jpg [cit. 2017-03-28] 61. Picture 61 – Reserpine 62. Picture 62 – Rauvolfia serpentine, Dostupné z: https://commons.wikimedia.org/wiki/File:Rauvolfia_serpentina_01.JPG [cit. 2017-03-28] 63. Picture 63 - Strychnine 64. Picture 64 – Lysergic acid 65. Picture 65 – LSD papers

66. Picture 66 - Quinoline 67. Picture 67 – Cinchoma officinalis, Dostupné z: https://commons.wikimedia.org/wiki/File:Cinchona_officinalis_(K%C3%B6hler) .jpg [cit. 2017-03-28] 68. Picture 68 - Quinine 69. Picture 69 - Quinidine 70. Picture 70 - Isoquinoline 71. Picture 71 – Papaver somniferum, Dostupné z: https://commons.wikimedia.org/wiki/File:Papaver_somniferum_(2).jpg [cit. 2017-03-28] 72. Picture 72 – Opium, Dostupné z: https://en.wikipedia.org/wiki/Papaver_somniferum#/media/File:Opium_pod_cut_ to_demonstrate_fluid_extraction1.jpg [cit. 2017-03-28] 73. Picture 73 - Papaverine 74. Picture 74 - Laudanosine 75. Picture 75 – Hydrastine 76. Picture 76 – Hydrastis Canadensis, Dostupné z: https://commons.wikimedia.org/wiki/File:Hydrastis_canadensis_(Kowal_garden) .jpg [cit. 2017-03-28] 77. Picture 77 -Reticuline 78. Picture 78 – Reticuline x Morphine 79. Picture 79 - Morphine 80. Picture 80 – Morphine (left) vs. heroin (right) 81. Picture 81 - Codeine 82. Picture 82 - Thebaine 83. Picture 83 - Berberine 84. Picture 84 - Berberis vulgaris, Dostupné z: https://commons.wikimedia.org/wiki/File:Berberis_vulgaris_munich.JPG [cit. 2017-03-28] 85. Picture 85 - Tubocurarine 86. Picture 86 - Chondronendron platiphyllum, Dostupné z: https://commons.wikimedia.org/wiki/File:Chondrodendron_platiphyllum_(A._St. -Hil.)_Miers._(8249538387).jpg [cit. 2017-03-28]

87. Picture 87 - Pyrrolizidine 88. Picture 88 - Senecio barbertonicus, Dostupné z: https://commons.wikimedia.org/wiki/File:Senecio.barbertonicus.7074.jpg [cit. 2017-03-28] 89. Picture 89 - Erechtites minima, Dostupné z: https://commons.wikimedia.org/wiki/File:Erechtites_minima.jpeg [cit. 2017-03-28] 90. Picture 90 – Crotalaria retusa, Dostupné z: https://cs.wikipedia.org/wiki/Soubor:Crotalaria_retusa_01.JPG [cit. 2017-03-28] 91. Picture 91 - Monocrotaline 92. Picture 92 – Quinolizidine 93. Picture 93 - Lupinine 94. Picture 94 – Lupinus luteus, Dostupné z: https://commons.wikimedia.org/wiki/File:Altramus_amarelo_(Lupinus_luteus)_- _panoramio.jpg [cit. 2017-03-28] 95. Picture 95 – Lupinus polyphyllus, Dostupné z: https://cdn.pixabay.com/photo/2013/03/19/03/47/lupine-94953_960_720.jpg [cit. 2017-03-28] 96. Picture 96 – Emetine 97. Picture 97 - Carapichea ipecacuanha, Dostupné z: https://commons.wikimedia.org/wiki/File:Psychotria_ipecacuanha_- _K%C3%B6hler%E2%80%93s_Medizinal-Pflanzen-251.jpg [cit. 2017-03-28] 98. Picture 98 – (-)-Sparteine 99. Picture 99 - Sarothamnus scoparius, Dostupné z: https://upload.wikimedia.org/wikipedia/commons/e/e1/333_Sarothamnus_scopar ius.jpg [cit. 2017-03-28] 100. Picture 100 - Imidazole 101. Picture 101 - Pilocarpine 102. Picture 102 – Pilocarpus jaborandi, Dostupné z: https://commons.wikimedia.org/wiki/File:Pilocarpus_pennatifolius_- _K%C3%B6hler%E2%80%93s_Medizinal-Pflanzen-238.jpg [cit. 2017-03-28] 103. Picture 103 - Muscarine

104. Picture 104 – Amanita muscaria, Dostupné z: https://commons.wikimedia.org/wiki/File:Amanita_muscaria_3_vliegenzwamme n_op_rij.jpg [cit. 2017-03-28] 105. Picture 105 - Purine 106. Picture 106 - Xanthine 107. Picture 107 - Theophylline 108. Picture 108 - Theobromine 109. Picture 109 – Theobroma cacao, Dostupné z: https://upload.wikimedia.org/wikipedia/commons/5/5a/Matadecacao.jpg [cit. 2017-03-28] 110. Picture 110 – Cocoa beans, Dostupné z: https://cdn.pixabay.com/photo/2016/11/22/19/45/cocoa-beans- 1850312_960_720.jpg [cit. 2017-03-28] 111. Picture 111 - Caffeine 112. Picture 112 – Coffea arabica, Dostupné z: https://upload.wikimedia.org/wikipedia/commons/6/68/Starr_070308- 5468_Coffea_arabica.jpg [cit. 2017-03-28] 113. Picture 113 – Arabica beans 114. Picture 114 – Coffea robusta, Dostupné z: https://cdn.pixabay.com/photo/2014/05/16/04/48/coffee-plantation- 345402_960_720.jpg [cit. 2017-03-28] 115. Picture 115 – Robusta beans 116. Picture 116 – Camellia sinensis, Dostupné z: https://upload.wikimedia.org/wikipedia/commons/7/71/Csinensis.jpg [cit. 2017-03-28] 117. Picture 117 - Solanidine 118. Picture 118 - Rubijervine 119. Picture 119 – Tomatidine 120. Picture 120 - Aconitine 121. Picture 121 – Aconitum firmum, Dostupné z: https://commons.wikimedia.org/wiki/File:Om%C4%9Bj_tuh%C3%BD_(Aconitu m_firmum).jpg [cit. 2017-03-28]

122. Picture 122 – Aconitum plicatum, Dostupné z: https://upload.wikimedia.org/wikipedia/commons/3/30/Aconitum_napellus_02.jp g [cit. 2017-03-28] 123. Picture 123 - Tropolone 124. Picture 124 - Colchicine 125. Picture 125 – Colchicum autumnale, Dostupné z: https://upload.wikimedia.org/wikipedia/commons/9/97/Colchicum_autumnale.jp g [cit. 2017-03-28]

Bibliographic note BÁRTA, A., 2017: Introduction to Alkaloids. Brno: Bachelor thesis. Masaryk University, Faculty of Education, Department of Physics, Chemistry and Vocational Education. 77 pp. Supervisor Jiří Šibor, Ph.D.

Bibliografický záznam BÁRTA, A., 2017: Introduction to Alkaloids. Brno: Bakalářská práce. Masarykova univerzita, Pedagogická fakulta, Katedra fyziky, chemie a odborného vzdělávání. 77 s. Vedoucí bakalářské práce Mgr. Jiří Šibor, Ph.D.

Annotation The bachelor thesis „Introduction to Alkaloids“ is a short textbook written in English that should provide students not only with basic information about the important members of the alkaloid group but also should initiate students´ interest in these amazing compounds. Although, the textbook is written in English it should not make any trouble to non-native speakers. The textbook gives information about compounds´ chemical structures, occurrence in nature and possible applications.

Anotace Bakalářská práce „Introduction to Alkaloids“ je anglicky napsaný učební materiál, jehož cílem je zaujmout studenty a poskytnout základní informace o nejdůležitějších Alkaloidech. Ačkoliv je práce napsána v angličtině, měla by být srozumitelná nejen pro rodilé mluvčí, ale také pro ty, kteří se angličtinu učí jako druhý jazyk. V práci jsou popsány chemické struktury vybraných látek, jejich výskyt v přírodě a také jejich možná použití.

Keywords Alkaloids; Chemistry; Textbook; Occurrence; Application.

Klíčová slova Alkaloidy; chemie; učebnice; výskyt; využití.