intro organic 2011

7/29/2019 Intro Organic 2011

1/30

Organic Chemistry In Our Everyday LifeProfessor Michael J . Krische

The properties of organic molecules depend upon their structures

Digitoxin - A Drug Based onDigitalis Extract Used toTreat Congestive Heart

Failure and Atrial Fibrillation

H3C

OH

H3C

OO

H3C

OHO

H

H

O

O

O

H3C

OHO

OH3C

OHHO

HH

Purple Foxglove, i.e.Digi talis P urpurea

Glycone - Modulates DrugDelivery and Metabolism

Steroidal Aglycon -

The "War-Head" ofDigitoxin

Plant Extraction

A Broad Scientific Question: What is the nature of matter?

Organic Chemistry: The study of carbon containing compounds. Sincevirtually all naturally occurring compounds contain carbon, organic

chemistry is inextricably tied to living systems.


2/30

Subtle Differences in Structure Confer Differences in Properties

Some Familiar Naturally Occurring Substances or Natural Products

N

N

Me

O

PopcornAroma

N

N

Me

Raw PotatoAroma

OMe

N

N

Bell PepperAroma

OMe

Me

Me

OH

OMe

O H

OH

OMe

VanillaAroma

CloveAroma

GrapeAroma

WintergreenAroma

O

OMe

NH2

OMe

O

OH



3/30

Naturally Occurring Fragrant Esters

Subtle Differences in Structure Confer Differences in Properties

CH3

RasberryAroma

OO

CH3

PearAroma

AppleAroma

O

O

CH3

H3C O CH3H3C

O

PineappleAroma

O CH3

OH3C

CH3

RumAroma

O

O

BananaAroma

OrangeAroma

O

O

CH3

H3C

H3C O(CH2)7CH3

O

PeachAroma

OH3C

H3C

CH3

CH3

O

HoneyAroma

OO

H3C



4/30

C C

(+)-Carvone(Caraway)

(-)-Carvone(Spearmint)

Mirror Plane

O O

HH

Left Hand Right Hand

Mirror Plane

Organic Molecules Can Have Handedness - They Can Be Chiral. Pair of Chiral

Molecular are Referred to as Enantiomers.

Tetrahedral Carbon Centers Possessing Four Different Groups Can Exist as Non-

Superimposable Mirror Images They are Enantiomers.

http://esg-www.mit.edu:8001/esgbio/chem/stereo.htmlhttp://esg-www.mit.edu:8001/esgbio/chem/stereo.htmlhttp://esg-www.mit.edu:8001/esgbio/chem/stereo.htmlhttp://esg-www.mit.edu:8001/esgbio/chem/stereo.htmlhttp://esg-www.mit.edu:8001/esgbio/chem/stereo.htmlhttp://esg-www.mit.edu:8001/esgbio/chem/stereo.htmlhttp://esg-www.mit.edu:8001/esgbio/chem/stereo.html


5/30

NC

N

O

O

O O

H

NC

N

O

O

OO

H

(+)-Thalidomide(Sedative, anti-Nausea)

(-)-Thalidomide(Severe Birth Defects)

H H

Mirror Plane

OH HS

Antidote forHg Poisening

Optical Atrophy(Blindness)

Mirror Plane

O

HO

O

SH

H3C

H3C

NH2H H2N HCH3CH3

Different Enantiomers Can Have Wildly Different Biological Profiles

O

O

OH

NH

O

O

O

O

CH3

OH

OOOH

H

OOO

H3CIf a molecule has n-chiral centers, there are 2n possiblecombinations possible, termed stereoisomers. The FDA

now requires that chiral molecules be prepared as single

entities. Over 50% of the worlds top-selling drugs are

single enantiomers and it is estimated that 80% of all drugscurrently entering development are chiral and will be

marketed as single-enantiomer entities.

Taxol - Bark of Pacific Yew Tree

Potent Anti-Cancer Agent

11 Stereocenters 2048 Possible Isomers!



6/30

Where Do Drugs Come From? 61% of the 877 small molecules introduced as drugs worldwide from 1981-2002 were inspired by NaturalProducts (J . Nat. Prod. 2003, 1022). Hence, the discovery, biological profiling (SAR),and preparation of natural products is of paramount importance in terms of public health.

Coriolin

(Anti-Tumor Properties)

H

H

CH3

CH3

CH3

OO

O OH

Hirsutic Acid-C

(Anti-Biotic Properties)

H

H

CH3

CO2H

CH3O

HO

The Structures of Natural

Products are Shaped by

Selective Pressure.

They Evolve.



7/30

H3C

OH

H3C

OO

H3C

OHO

H

H

O

O

O

H3C

OHO

O

H3C

OHHO

HH

Purple Foxglove, i .e.Digitalis Purpurea

Glycone - Modulates DrugDelivery and Metabolism

Steroidal Aglycon -The "War-Head" of

Digitoxin

PlantExtraction

Digitoxin - A drug based on digitalis extract used to treat congestive heart failure and atrial fibrillation. Theextracts of purple foxglove, i.e. digitalis purpurea, have been used in folk-medicine since 1500 B.C. In 1775, theScottish doctor Withering determined that the extract of purple foxglove was the active ingredient in a folk

remedy treatment for heart conditions prepared by a local gypsy woman. In this way, digitoxin was introduced tothe mainstream medical community. It is still in broad use today.



8/30

O

OEtHN

Vasotec - Merck & Co.

$2.3 Billion in Sales (1999)

CH3

ON

CO2H

O

OHHN

Zestril - AstraZeneca Plc.

$1.2 Billion in Sales (1999)

ON

CO2H

NH22

Cardiovascular Drugs - Antihypertensive Agents: Angiotensin-converting enzyme (ACE) plays akey role in regulating blood pressure. ACE cleaves the peptide angiotensin I to give angiotensin II, which is a

strong vasoconstrictor.The venom of the Brazilian pit viper was found to inhibit ACE cleavage. Even though the

snake venom peptides were not orally active, the realization that peptides could inhibit ACE initiated the searchfor smaller peptide based inhibitors which could be administered orally. In this way, the venom of the Brazilian

Pit Viper served as inspiration for the blockbuster antihypertensive agents Vasotec and Zestril.

Venom of the Brazilian Pit Viper

Teprotide is a 9-Amino Acid PeptidePyr-Trp-Pro-Arg-Pro-Gln-Ile-Pro-Pro

http://www.fasebj.org/content/vol18/issue3/images/large/385031677007.jpeg


9/30

Diabetes - Exenatide (marketed as Byetta): Diabetes afflicts 23.6 million children and adults in theUnited States (7.8% of the population). Type 2 Diabetes (adult-onset diabetes) is a metabolic disorder that is

primarily characterized by insulin resistance, insulin deficiency, and hyperglycemia. It is often managed by

increasing exercise and dietary modification, although medications and insulin are often needed, especially asthe disease progresses. Exenatide, a 39-amino-acid peptide, is a synthetic version of exendin-4, a hormone in

the saliva of the Gila monster that regulates glucose metabolism and insulin secretion.

http://upload.wikimedia.org/wikipedia/commons/c/ce/Gila_Monster_head.jpg


10/30


Halichondrin B Analogue Eribulin (Halaven): Halichondrin Bis a naturally-occurring polyether macrolide originally isolated

from the marine sponge Halichondira okadai by Hirata and Uemura

in 1986. It was found to exhibit extraordinary in vitro and in vivoanti-cancer activity. The first total synthesis was completed by

Yoshito Kishi and co-workers at Harvard University in 1992. Later, a

simplified analogue of Halichondrin B was developed named

Eribulin (marketed as Halaven). Eribulin has an IC50 value of 13.0

nM for DLD-1 human colon cancer cell and exhibits antitumor

activities in melanoma, breast and other cell lines. Eribulin disrupts

microtubule assembly during mitosis, which inhibits cell division.Eribulin was approved by the U.S. Food and Drug Administration

on November 15, 2010, to treat patients with metastatic breast

cancer who have received at least two prior chemotherapy

regimens for late-stage disease.
http://upload.wikimedia.org/wikipedia/commons/8/81/Sponge.noaa.jpg


11/30

Analgesics - Morphine: Used as early as 4000 BC, the main ingredient of opium, it was not until 1803 thatMorphine was first identified and isolated by the German pharmacist Serturner. He called this alkaloid "Morphia"

after Morpheus, the Greek God of Dreams. Morphine is used medicinally to alleviate severe pain. Morphine was

used during the American Civil War as a surgical anesthetic and was sent home with many soldiers for relief ofpain. At the end of the war, over 400,000 people had the army disease, morphine addiction.

ONMe

MeO

HO

ONMe

AcO

AcO

Morphine Codeine Heroin

ONMe

HO

HO

From the opium poppy pod, used as early as 4000 BC

Has potent analgesic and euphoric properties

Composes 10-15% of dry weight of the poppy

95% of morphine extracted is converted to codeine

Illicit production of morphine exceeds licit production

by a factor of 10.

http://www2.aros.net/~lambo/seeds/seeds.htmhttp://www2.aros.net/~lambo/seeds/seeds.htmhttp://www2.aros.net/~lambo/seeds/seeds.htmhttp://www2.aros.net/~lambo/seeds/seeds.htmhttp://www2.aros.net/~lambo/seeds/seeds.htm


12/30

Analgesics - Aspirin and the Willow Tree: The father of modern medicine, Hippocrates, who livedsometime between 460 B.C and 377 B.C. left historical records of pain relief treatments, including the use of powder

made from the bark and leaves of the willow tree to heal headaches, pains and fevers. The active ingredient in willow

bark, termed salicin, was isolated in 1828, by Buchner, a pharmacy professor of at the University of Munich. By 1829,the French chemist Leroux improved the extraction procedure, obtaining ~30g of salicin from 1.5kg of willow bark.

Later, in 1838, the Italian chemist Piria split salicin into a sugar and an aromatic component (salicylaldehyde) and

converted the latter, by hydrolysis and oxidation, to a crystalline, colorless acid, that he named salicylic acid.

However, salicylic acid was tough on stomachs. In 1853, Gerhardt neutralized salicylic acid by buffering it with sodium

(sodium salicylate) and acetyl chloride, creating acetylsalicylic acid. Gerhardt had no desire to market his product and

abandoned his discovery. In 1899, the German chemist Hoffmann, who worked for Bayer, rediscovered Gerhardt's

formula, and gave it to his father who was suffering from arthritis. With good results, Felix Hoffmann convinced Bayer

to market the new wonder drug. Aspirin was patented on March 6, 1889.

O

Acetosalicylic Acid

O CH3

O

OH



13/30

Warfarin: An anti-coagulant that is the top prescribed blood thinning agent in the world.

In the 1930s, a cow farmer in Deer Park, Wisconsin, brought samples of the sweet clover his cows were eating to

the University of Wisconsin, searching for an explanation for his cows death by excessive bleeding after minorprocedures. Upon analysis of the cows blood, low levels of blood coagulation proteins were found. Extraction

and isolation of products in the sweet clover silage produced the compound later known as warfarin, which

inhibits the production of blood coagulation factors.

In the 1940s, warfarin first was patented as a highly effective rat poison and soon became the highest used rat

poison in the world. A decade later, its therapeutic anticoagulant potential was realized, now as the most utilized

anticoagulant for treatment for thrombosis and prevention of embolisms, especially post cardiac surgery.

Warfarin

Rat Poison to Top-Selling Anticoagulant



14/30

Physostigmine: This alkaloid acts as a cholinesterase inhibitorand is naturally found in the calabar bean plant, native to Nigeria. Its

biological activity results from blocking the breakdown of

acetylcholine, a chemical responsible for nerve signal transmission.

Ingesting large quantities of physostigmine results in death by

asphyxiation, but small quantities have been found to have a wide

range of therapeutic applications, including treatment of glaucoma,

Alzheimers disease, myasthenia gravis (an autoimmune disease

causing muscle weakness), and as an antidote for several toxins.


One important side effect is nausea and vomiting, which plays an important role in the historical significance

of physostigmine and calabar bean.

In the past, calabar bean was used in trial by ordeal by the Efik Uburutu people in Nigeria to determine if a

suspected person was guilty of a crime. After ingesting an herbal drink containing ground calabar bean, if the

suspect vomited, they were declared innocent. If they didnt vomit, the suspect was declared guilty, and

would die soon after. Medicinal applications of physostigmine-containing calabar bean were first studied in

1864, and further development has resulted in a powerful therapeutic agent.


15/30

Analgesics - Non-Steroidal Anti-Inflammatory Drugs (NSAIDs): NSAIDs are analgesic andantipyretic drugs that inhibit the enzymes cyclooxgenase 1 and 2 (COX-1/COX-2) from synthesizing prostaglandins,

chemicals in cells that promote inflammation, pain and fever. This mechanism of prostaglandins inhibition was

discovered by Sir John Robert Vane (1927-2004), a British pharmacologist, who was later awarded a Nobel Prize for hiswork in 1982. NSAIDs are used in the treatment of conditions where pain and inflammation are present, e.g. arthritis,

osteoarthritis, dysmenorrhea, gout etc. Since prostaglandins support blood clotting function of the platelets, heavy or

frequent use of NSAID can result in an ulcer or prolonged bleeding, especially after an injury or a surgery.

NSAIDs are mostly weak acids with a pka of 3-5. The first class of anti-inflammatory, analgesic and antipyretic drugs in

the family of NSAID were the salicylates (e.g. aspirin). NSAIDs can be differentiated by their potency, duration of action,

methods of administration and rate of elimination, and can be classified based on their chemical structures.

Most NSAIDs are available over-the-counter without prescription; in 2001, it was reportedthat NSAIDs account for 70 million prescriptions and 30 billion over-the-counter

medications sold in the United States.



16/30

Ibuprofen (Advil, Motrin, etc.): Phenylpropionic acid derivative that was derived from

propionic acid and was discovered by Boots Group (Steward Adams and coworkers); it

was patented in 1961. It originally marketed as Brufen; it is commonly used as an

analgesic and anti-inflammatory medicine especially for the treatment of rheumatoidarthritis. It was listed as one of the essential medicines for a basic health system by the

World Health Organization (WHO) in 2005.

Naproxen (Aleve etc.): Phenylpropionic acid derivative that is commonly used for thetreatment of moderate to severe pain and inflammation associated with arthritis. It was

first marketed as a prescription drug (Naprosyn) in 1976 and became available over-the-

counter as naproxen sodium (Aleve) in 1994.

Ketoprofen (Orudis, Oruvail, etc.): Phenylpropionic acid derivative that is commonly

used for treatment of inflammatory pain associated with arthritis. It is a racemate with

only the (S)-enantiomer possessing pharmacological activities. It is also a common

analgesic and is used fever-reducing in horses and some small animals.

Diclofenac (Voltaren, Olfen, etc.): Phenylacetic acid derivative that is commonly

used for the treatment of inflammation and joint pain caused by rheumatoid arthritis,osteoarthritis, ankylosing spondylitis etc. It was developed by Ciba Geigy (now Novartis)

in 1973 and was first introduced into the UK in 1979.

Ketorolac (Toradol, Acular): Heterocyclic acetic acid derivative that was approved

by FDA in 1989. Recent studies showed that it is effective for reducing post-operative

pain. This drug is not available over-the-counter in the United States and a prescription

is required for administration.

Analgesics - Non-Steroidal Anti-Inflammatory Drugs (NSAIDs)



17/30

Antiseptics (external infection): Carbolic acid, also known as phenol, was introduced by the Englishsurgeon Lister the first effective anti-septic in 1867. In the middle of the nineteenth century, post-operative sepsis

infection accounted for the death of approximately 50% of the patients undergoing major surgery. By cleaning

wounds and dressing them using carbolic acid solutions, he was able to announce at a British Medical Association

meeting, in 1867, that his wards at the Glasgow Royal Infirmary had remained clear of sepsis for nine months. Phenol

is caustic to skin, so subsequently the milder antiseptic boric acid (H3BO3) was used. Antisepsis was one of the two

most significant medical discoveries in the 19th century (the second was anesthesia).

HO

Carbolic AcidPhenol



18/30

Anti-Bacterials (internal infection): Antibiotics are natural substances that are released by bacteria andfungi as a means of inhibiting other organisms - it is chemical warfare on a microscopic scale.

Paul Ehrlich, a German medical professor, was fascinated that aniline and other synthetic dyes stain specific microbes.

This led him to predict that one could create "magic bullets," agents that would "be able to exert their full action

exclusively on the parasite harbored within the organism." Focusing on syphilis, a bacterial infection that afflicted over

10% of the European population, he screened compounds that contained aniline substructures (for delivery) and

arsenic (the warhead), he identified arshpenamine orSalvarsan in 1909. His search for a specific drug to treat a

specific disease marked the beginning of targeted chemotherapy. Salvarsan was the world's first blockbuster drug.

Earlier, syphilis was treated using mercury salts.

In 1932, the German biochemistry Domagk discovered that the sulfanilimide dye, later named prontosil, killed

bacteria without serious toxic side effects. At this time, Domagks 6-year old daughter received a streptococcalinfection from a needle prick and was near death. Domagk tested the drug on his daughter, who made a complete

recovery. Later it was found that the much simpler substance, sulfanilamide, is superior and much cheaper to produce

also, it doesnt lead to red skin! The discovery of sulfanilamide greatly attenuated the mortality rate during WWII.

Penicillin was discovered of by Alexander Fleming in 1928, but it wasn't until ten years later, in 1939, that Chain, Florey

and Abraham of Oxford University were able to purify and stabilize a form of penicillin, enabling demonstration of its

therapeutic potential. Penicillin is produced from a soil mold via fermentation. When penicillin became widely availableduring the second world war, it was a medical miracle, rapidly vanquishing the biggest wartime killer - infected

wounds. Penicillin has saved countless lives and is considered the greatest discovery in medical history.

HO As

ClH3N

As OH

NH3Cl

ArsphenamineSalvarsan

NO

HN

O

CO2H

Penicillin VSulfa-DrugsProntosil (Sulfonilamide)

H2N N N SO2NH2

NH2OPh



19/30

Streptomycin and Tuberculosis The WhitePlague: Despite its wonders, penicillin is not effectiveagainst tuberculosis a bacterial infection of the lung. During the 19th century, up to 25 per cent of deaths in Europe

were caused by this disease (although 90% of infections are asymptomatic). Over the past two centuries, TB has

claimed over 2 billion lives. A third of the world's population are thought to be infected with M. tuberculosis, and new

infections occur at a rate of about one per second.Streptomycin is antibiotic produced by soil bacteria originally isolated by Waksman and Schatz in 1947. It is a

mainstay of tuberculosis therapy. Because streptomycin-resistance arises during treatment, the antibiotic is usually

used in combination with other drugs, such as isoniazid or rifampicin, another natural product from soil bacteria

isolated in 1957. Despite all the drugs available today, TB is still a problem in developing nations. The highest

incidences (up to 80%) are in countries in Africa, Asia, and Latin America only 5 10% of the US population tests

positive for TB. The World Health Organization estimates that each year 3 million people die from TB. Today, there are

strains of TB resistant to any known antibiotic. In New York City, 19% of TB is resistant to the two most powerful drugs.

It is now feared that the disease will spread to other areas in the U.S. before there is a cure.

Green Chemistry for Organic SynthesisProf. M. J . Krische
http://upload.wikimedia.org/wikipedia/commons/8/8e/TB_poster.jpg


20/30

O

O

OH

Me

OH

Me

OH

MeMe

O

Me

OH

Me

Me

OH

O

OH

Me

OH

Me

OH

MeMe

O

Me

OH

Me

Me

OHErythromycin A

Erythromycin A Seco Acid

7 polypriopionate units

Azithromycin

O

O

Me

MeHO

Me

O

HO

Me

MeO

MeMe

HOO Me

NMe2HO

O Me

MeOH

OMe

N

O

Me

O

MeHO

Me

O

HO

Me

MeO

MeMe

HOO Me

NMe2HO

O Me

MeOH

OMe

Me

Erythromycin: Erythromycin is another natural product made by soil bacteria that has anti-biotic activity similar topenicillin. Indeed, it is often given to people who are allergic to penicillin. Erythromycin was discovered by the

pharmaceutical company Eli Lilly. Erythromycin is constructed via polypropionate biosynthesis, which involves formal

aldol-type bond constructions. The aldol reaction ranks among the most important methods for the stereoselectivesynthesis of polyketide natural products both in Nature and in synthetic organic chemistry.

Azithromycin is a synthetic analogue of erythromycin, and one of the words top-selling drugs. It is used to treat

bacterial infections such as ear infections, tonsillitis, throat infections, laryngitis, bronchitis, and pneumonia.



21/30

Quinine & Malaria: The Cinchona tree was originates from the slopes of the Andes. Its ability to cure malariawas discovered by Jesuit monks and the anti-malarial value of Cinchona became more widely recognized. So valuable

was the bark that at one time, bark powder was often matched by its weight in gold. Indeed, over-harvesting of the bark

nearly decimated the population of the tree in its native habitat. Fortunately, Dutch adventurers smuggled a few

seedlings out of Peru in the 1860s, and used them to set up large plantations in Java. In WWII, the Japanese militaryconquest cut off access to quinine from Java, which accounted for 95% of the world supply. This led to the death of

over 60,000 US troops died in WWII due to malaria infection.

Currently, an estimated 200 million to 300 million malaria infections occur each year, with 2 million to 3 million deaths

one death every 12 seconds. 90% of all cases occur in Africa. 5% of African children (3,000 each day) die of malaria.

The World Health Organization (WHO) ranks malaria first among human parasitic diseases in terms of socio-economic

and public health importance. Due to global warming and drug-resistantance, malaria is undergoing a dramatic

resurgence. Since recorded history until today, more human deaths are attributed to malaria than any other cause.

Green Chemistry for Organic SynthesisProf. M. J . Krische


22/30

Sugar Substitutes: A total of 3,920 products containing artificial sweeteners were launched in the U.S. between 2000and 2005. Artificial sweeteners are much less expensive than sucrose or corn syrup.

Saccharin: Synthesized in 1879 by Remsen and Fahlberg, it is 300-500 times as sweet

as sugar and is often used to improve the taste of toothpastes, dietary foods, and dietary

beverages. It is marketed as Sweet n Low.

Cyclamate: Discovered in 1937 at the University of Illinois by graduate student Michael

Sveda, the FDA banned its sale in the United States in 1969 because intestinal bacteria

could desulfonate cyclamate to produce cyclohexylamine, a compound suspected to havesome chronic toxicity.

Aspartame: Discovered in 1965 by James M. Schlatter, it is 180 times sweeter than

sucrose. This sweetener is marketed under a number of trademark names, including Equal,

NutraSweet, and Canderel. It is used in approximately 6,000 consumer foods and

beverages.

Sucralose: Discovered in 1976 by Leslie Hough, sucralose was first approved for use in in

1998. It is 600 times as sweet as sucrose and can be found in more than 4,500 food and

beverage products. It is used because it is a no-calorie sweetener and is safe for

consumption by diabetics. It is marketed as Splenda.



23/30

Cyclopamine: Cyclopamine is an alkaloid identified as 11-deoxojervin that is found in Veratrumcalifornicum, the California corn lily. It was named for one-eyed lambs, real-world Cyclopes, at afarm in Idaho. The U.S. Department of Agricultures Poisonous Plant Research Laboratory in Utah

began an investigation on this alkaloid after World War II due to the 40% loss of sheep resulting fromthe cyclopean defect in this region. It was found that if pregnant sheep ate the plant on their 14th day of

gestation, they would give birth to lambs with a single eye in the middle of their foreheads. Ingestion

of this plant during the later days of gestation induces limb and tracheal malformations.

Upon further study, it was revealed that cyclopamine inhibits the hedgehog (Hh) signaling pathway

that regulates embryogenesis. This finding attracted the attention of many developmental biologists

and cancer researchers. An organic chemist from the University of Leipzig in Germany, Athanassios

Giannis, reported that aberrant activation of this Hh-pathway in adults leads to malignances. As a

result, cyclopamine could be a potential therapeutic agent for the treatment of some challenging forms

of cancer.


O C O f


24/30

Coniine: Coniine is a toxic alkaloid found in poisonous hemlock (coniummaculatum). It is a neurotoxin that targets the peripheral nervous system.Coniine causes ascending muscle paralysis by blocking the nicotinic

receptors on the post-synaptic membrane of the neuromuscular junction.Once paralysis reaches the respiratory muscles, death occurs due to lack of

oxygen to the heart and brain. In ancient Greece, the philosopher Socrates

was poisoned by hemlock after being condemned to death for impiety.

Coniine also is found in the nectar of the yellow pitcher plant (Sarraceniaflava), where it is used to intoxicate prey. Made by Albert Ladenburg in 1886,coniine is the first alkaloid prepared via total synthesis. For an adult, theingestion of more than 100 mg of coniine (6 to 8 fresh leaves, or a smaller

dose of seeds or root) may result in fatality.


h d


25/30

Organic Chemistry and Drug DiscoveryProfessor Michael J. Krische

Atropa belladonna: Atropa belladonna is a botanical name for plants that are commonly known asbelladonna; other common names include deadly nightshade, atropa, deaths herb and witchs berry.

Atropa belladonna belongs to the Solanaceae family, which is commonly known as the nightshade or

potato. Belladonna has been used for its hallucinogenic effects, cosmetic, poison and medicine. Theword Belladonna comes from the Italian words that mean beautiful lady, this is probably because

italian women used to dilate their pupils by means of a drop of belladonna in each eye. The name

atropa bella donna is derived from a warning in Italian and Greek meaning do not betray a beautiful

lady.

Active ingredients in Belladonna are atropine, hyoscine, and hyoscyamine, which possess

anticholinergic properties. All parts of this plant may prove to be poisonous even in small dosage,especially the black berry. 10 to 20 ingestions of the black berry will kill most adults, and two to three

will be sufficient to kill the children. Belladonna poisoning has symptoms such as fever, dry mouth,

loss of balance, sensitivity to light, rash, hallucination, urinary retention, constipation, convulsion aswell as staggering headache.

O i Ch i t I O E d Lif


26/30

Oenanthotoxin: Oenanthotoxin is a toxin extracted from Oenanthecrocata; it is a central nervous system poison that causes facial musclesspasm resulting in a grinning appearance, a trait that is anciently known as

risus sardonicus the sardonic smile. This plant was used in ritualkillings in ancient pre-Rome times in Sardinia. Elderly citizens who were

unable to support themselves were seen as a burden to society. Hence, they

were intoxicated with this sardonic herb prior to being killed by beating or

dropping from a high rock, so they would have a defiant grin in the face of

death. Researchers later discovered that the plant toxins oenanthotoxin and

dihydrooenanthotoxin block the receptors to the neurotransmitter -aminobutyric acid (GABA), which is directly involved in muscle tone

regulation. The sardonic smile could be explained on the basis of this

observation.




27/30

Poison Dart Frogs: Skin secretions from certain frogs are used byAmerindian tribes to prepare poison darts. The golden poison arrow

frog (Phyllobates terribilis) is most deadly to humans. Its skin

secretions contain the potent cardio- and neurotoxic steroidal alkaloidbatrachotoxin. Frogs raised in captivity do not produce this toxin, as

they acquire the poison from eating insects in their native habitat,

which obtain the poison from a plant source. Approximately 136

micrograms of batrachotoxin, equivalent to 2-3 grains of table salt, is a

lethal dosage. Compounds isolated from these frogs have potential

medicinal value. For example, the alkaloid epibatidine, isolated from

the skin secretions of the frog Epipedobates tricolor, is a painkiller 200times as potent as morphine. Many of these frogs are now endangered

due to habitat loss.


http://upload.wikimedia.org/wikipedia/commons/6/6f/Epipedobates_tricolor1.jpg


28/30

Ergotism and Witchcraft: The fungus Clavicepspurpurea infects rye and produces metabolites known asthe ergotalkaloids, which are used to produce lysergic

acid and its infamous diethylamide, known as LSD.Ingesting infected rye bread causes a form of food

poisoning called ergotism, which is characterized by

violent muscle spasms, vomiting, hallucinations,

paranoia, crawling sensations on the skin, and even a

form of gangrene known as St. Anthonysfire.

Plagues of Holy Fire (gangrenous ergotism)

are responsible for certain geographical boundaries in

modern Europe. For example, France suffered many

waves of ergotism in the 8th and 9th centuries. Thousands

died, which made France an easy target for Vikings. These

Northmen took the northwest coast of France, which

ceded to them and would become Normandy.

Ergot thrives in warm, damp, rainy springs and

summers. There is considerable evidence that ergotism is

linked to medieval witch trials. Bouts of bewitchmenttended to be seasonal and would recur in geographical

regions where rye is a staple. Additionally, witch trials

were more common in years when the spring and summer

months were colder and wetter. Ergot alkaloids were

found in the stomachs of Iron Age human remains from

peat bogs northeastern Europe.




29/30


Industrial Chemistry: Where do chemical products come from? Is their production sustainable?One major feedstock for the production of organic compounds is methane, the primary component of

natural gas. In the chemical industry, methane is the feedstock of choice for the production of

hydrogen, methanol, acetic acid, and acetic anhydride. In fact, 2% of global energy consumption isdue to methane-steam reforming to produce the hydrogen needed for the Haber-Bosch reaction the

reduction of atmospheric nitrogen to furnish ammonia. Ammonia is the limiting nutrient in terrestrial

plant growth and NH4NO3 produced using the Haber-Bosh process is a potent fertilizer that bolstered

worldwide food production to unprecedented levels. As natural sources of methane are depleted,

efforts toward the production and capture of methane from landfills and other renewable sources has

become the topic of intensive investigation.

Organic Chemistr In O r E er da Life


30/30


An Example of Industrial Synthesis on Scale: Di(2-Ethylhexyl) Phthalate

> 50% Plasticizer!

4 Linear Steps, H2O is Only Stoichiometric Byproduct

Catalytic Chemistry versus Stoichiometric Reagent

Abundant Starting Materials -Minimal Preactivation

intro organic 2011

Documents